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COVID-19 research v0.374 IRF5 Rebecca Foulger Classified gene: IRF5 as Green List (high evidence)
COVID-19 research v0.374 IRF5 Rebecca Foulger Added comment: Comment on list classification: Green rating suggested after initial triage by Illumina curation team. Kept rating as Green following literature review: PMID:29375210 demonstrate that polymorphisms in IRF5 can affect viral disease progression. Functional studies and animal models (fish and mice) show that IRF5 is required for antiviral immunity. Therefore on balance, kept rating as Green.
COVID-19 research v0.374 IRF5 Rebecca Foulger Gene: irf5 has been classified as Green List (High Evidence).
COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:30457675. Chow et al., 2019 examined IRF5-dependent gene expression and found that loss of IRF5 in mice resulted in modest and subtle changes in the expression of West Nile Virus (WNV)-regulated genes.
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COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:21240265. Krausgruber et al., 2011 state that polymorphisms in IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively, defining a role for IRF5 as a transcriptional repressor.
COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:29079574. Cevik et al., 2017 identify IRF5 as an important suppressor of HCV replication and HCC pathogenesis.
COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:29375210. Sy et al., 2018 investigated possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and liver disease outcomes. Comparing patients and controls, no significant association was observed in viral load for the four IFR5 variants studied, but alleles rs13242262T and rs10488630G contributed to an increased risk of liver cirrhosis. The process of liver cirrhosis in HBV infection is a results of the interplay between viral factors and host immune responses suggesting that IRF5 haplotypes appear to influence the outcome of HBV infection.
COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:32075938. Forbester et al., 2020 use human-induced pluripotent stem cells (hIPSCs) with biallelic mutations in IRF5, and showed that IRF5 deficiency corresponded with reduced influenza virus-induced inflammatory cytokine production.
COVID-19 research v0.373 IRF5 Rebecca Foulger commented on gene: IRF5: PMID:17360658. Yanai et al., 2007. Mouse model: authors show that IRF5 is critical for antiviral immunity by showing that Irf5(-/-) mice are highly vulnerable to viral infections.
COVID-19 research v0.373 IRF5 Rebecca Foulger Publications for gene: IRF5 were set to 17360658; 32075938; 29375210; 29079574; 1240265; 30457675
COVID-19 research v0.372 IRF5 Rebecca Foulger Publications for gene: IRF5 were set to
COVID-19 research v0.371 TNFSF10 Rebecca Foulger Classified gene: TNFSF10 as Amber List (moderate evidence)
COVID-19 research v0.371 TNFSF10 Rebecca Foulger Added comment: Comment on list classification: Kept the Amber rating initially suggested by Illumina curation team: plays a role in viral surveillance, and virus can modulate TNFSF10 (TRAIL) signaling. Many studies look at expression levels following infection. No direct susceptibility studies, so Amber appropriate.
COVID-19 research v0.371 TNFSF10 Rebecca Foulger Gene: tnfsf10 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.370 TNFSF10 Rebecca Foulger Publications for gene: TNFSF10 were set to 18802095; 14702109; 31725732; 27740879; 17913827; 15110181
COVID-19 research v0.369 TNFSF10 Rebecca Foulger changed review comment from: Summary of literature: TNFSF10/TRAIL is a death ligand that contributes to immune surveillance against virus-infected cells via the death receptor TNFRSF10B/DR5. TNFSF10 binding induces the caspase cascade to kill the virus-infected cell. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling.; to: Summary of literature: TNFSF10/TRAIL is a death ligand that contributes to immune surveillance against virus-infected cells via the death receptor DR5. TNFSF10 binding induces the caspase cascade to kill the virus-infected cell. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling.
COVID-19 research v0.369 TNFSF10 Rebecca Foulger commented on gene: TNFSF10: Summary of literature: TNFSF10/TRAIL is a death ligand that contributes to immune surveillance against virus-infected cells via the death receptor TNFRSF10B/DR5. TNFSF10 binding induces the caspase cascade to kill the virus-infected cell. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling.
COVID-19 research v0.369 VPS4A Sarah Leigh Publications for gene: VPS4A were set to
COVID-19 research v0.368 VPS4A Sarah Leigh reviewed gene: VPS4A: Rating: ; Mode of pathogenicity: None; Publications: 17928862, 30615963; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.368 TNFSF10 Rebecca Foulger Publications for gene: TNFSF10 were set to 18802095; 14702109
COVID-19 research v0.367 TPH1 Sarah Leigh Publications for gene: TPH1 were set to
COVID-19 research v0.366 TPH1 Sarah Leigh changed review comment from: TPH1 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
Using lymphocytic choriomeningitis virus in a Cd8-positive T cell-dependent mouse model of immunopathologic hepatitis, PMID 18516052 showed that Tph1-deficient mice, but not wildtype mice, normalized hepatic microcirculatory dysfunction, accelerated clearance of virus from liver, and reduced Cd8-positive T cell-dependent liver cell damage (reviewed by Alison Coffey and team, Illumina).; to: TPH1 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
TPH1 is part of the pathway for the synthesis of the neurotrasmitter serotonin.
Using lymphocytic choriomeningitis virus in a Cd8-positive T cell-dependent mouse model of immunopathologic hepatitis, PMID 18516052 showed that Tph1-deficient mice, but not wildtype mice, normalized hepatic microcirculatory dysfunction, accelerated clearance of virus from liver, and reduced Cd8-positive T cell-dependent liver cell damage, therefore it has been concluded that vasoactive serotonin supports virus persistence in liver and aggravates virus-induced immunopathology. (reviewed by Alison Coffey and team, Illumina).
COVID-19 research v0.366 TPH1 Sarah Leigh Classified gene: TPH1 as Red List (low evidence)
COVID-19 research v0.366 TPH1 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or in Gen2Phen.
COVID-19 research v0.366 TPH1 Sarah Leigh Gene: tph1 has been classified as Red List (Low Evidence).
COVID-19 research v0.365 TPH1 Sarah Leigh reviewed gene: TPH1: Rating: ; Mode of pathogenicity: None; Publications: 18516052; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.365 TNFSF4 Sarah Leigh changed review comment from: TNFSF4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
Tumor necrosis factor (TNF) family cytokines function as prominent mediators of immune regulation and the inflammatory response. Most TNF family cytokines are expressed as type II transmembrane proteins, with homology confined to approximately 150 C-terminal residues. The TNF ligands interact with a parallel family of receptors (reviewed by Alison Coffey and team, Illumina).
TNFSF4 is a cell surface glycoprotein antigen that is expressed in T-cell leukemia virus type 1 (HTLV-1) infected human cells (PMID 7913952;8076595). Functional analysis showed that anti-TNFSF4 monoclonal antibody inhibited T-cell proliferation (PMID 11359859).; to: TNFSF4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
Tumor necrosis factor (TNF) family cytokines function as prominent mediators of immune regulation and the inflammatory response. Most TNF family cytokines are expressed as type II transmembrane proteins, with homology confined to approximately 150 C-terminal residues. The TNF ligands interact with a parallel family of receptors (reviewed by Alison Coffey and team, Illumina).
TNFSF4 is a cell surface glycoprotein antigen that is expressed in T-cell leukemia virus type 1 (HTLV-1) infected human cells (PMID 7913952;8076595). Functional analysis showed that anti-TNFSF4 monoclonal antibody inhibited T-cell proliferation (PMID 11359859).
PMID 31725732: suggests that TNFSF4, one of the major causative cytokine factors in African swine fever virus pathogenesis, via inducing apoptosis.
COVID-19 research v0.365 TNFSF4 Sarah Leigh Publications for gene: TNFSF4 were set to 7913952; 8076595; 11359859
COVID-19 research v0.364 TLR5 Sarah Leigh changed review comment from: TLR5 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
The transmembrane protein TLR5 is a component of the immune system that is highly expressed in intestinal mucosa and recognizes bacterial flagellin (PMID 20203013)(reviewed by Alison Coffey and team, Illumina).
PMID 25395539 reports that mice treated with bacterial flagellin prevented rotavirus (RV) infection and cured chronically RV-infections. This processed required the flagellin receptors Tlr5 and Nlrc4. Flagellin-induced activation of Tlr5 on dendritic cells elicited production of the cytokine Il22, resulting in a protective gene expression program in intestinal epithelial cells. Administration of Il22 to mice reproduced the capacity of flagellin to prevent or cure RV. It was proposed that activation of innate immunity with flagellin, via Tlr5 inducing IL22 could be useful in preventing or curing viral infections.; to: TLR5 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
The transmembrane protein TLR5 is a component of the immune system that is highly expressed in intestinal mucosa and recognizes bacterial flagellin (PMID 20203013)(reviewed by Alison Coffey and team, Illumina).
PMID 25395539 reports that mice treated with bacterial flagellin prevented rotavirus (RV) infection and cured chronically RV-infections. This process required the flagellin receptors Tlr5 and Nlrc4. Flagellin-induced activation of Tlr5 on dendritic cells elicited production of the cytokine Il22, resulting in a protective gene expression program in intestinal epithelial cells. Administration of Il22 to mice reproduced the capacity of flagellin to prevent or cure RV. It was proposed that activation of innate immunity with flagellin, via Tlr5 inducing IL22 could be useful in preventing or curing viral infections.
COVID-19 research v0.364 TLR4 Sarah Leigh changed review comment from: Comment on list classification: Although this gene has not been associated with a phenotype in OMIM nor Gen2Phen, an animal model and two population studies indicate that deletion or the minor alleles of rs4986790 or rs4986791 are all associated with susceptibility to respiratory syncytial virus (RSV). The recently published article speculates that TLR4 could be involved in recognizing SARS‐CoV‐2 and proposes the selective targeting of TLR4‐spike protein interaction to treat COVID‐19 (PMID 32383269).; to: Comment on list classification: Although this gene has not been associated with a phenotype in OMIM nor Gen2Phen, an animal model and two population studies indicate that deletion or the minor alleles of rs4986790 or rs4986791 are all associated with susceptibility to respiratory syncytial virus (RSV). The recently published article speculates that TLR4 could be involved in recognizing SARS‐CoV‐2 and proposes the selective targeting of TLR4‐spike protein interaction to treat COVID‐19 (PMID 32383269).
COVID-19 research v0.364 TLR4 Sarah Leigh changed review comment from: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T399I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for p.D299G and p.T399I compared with control frequencies of 10.5% and 6.5%, respectively.

PMID 32383269 reports that: cell surface TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 and speculates that selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19.; to: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T399I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for p.D299G and p.T399I compared with control frequencies of 10.5% and 6.5%, respectively.
PMID 32391647 reports: Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV-carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF-κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.
PMID 32383269 reports that: cell surface TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 and speculates that selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19.
COVID-19 research v0.364 TLR4 Sarah Leigh Publications for gene: TLR4 were set to 11062499; 17579031; 17709532; 32383269
COVID-19 research v0.363 TLR4 Sarah Leigh Publications for gene: TLR4 were set to 11062499; 17579031; 17709532
COVID-19 research v0.362 TLR4 Sarah Leigh changed review comment from: Comment on list classification: Although this gene has not been associated with a phenotype in OMIM nor Gen2Phen, an animal model and two population studies indicate that deletion or the minor alleles of rs4986790 or rs4986791 are all associated with susceptibility to respiratory syncytial virus (RSV).; to: Comment on list classification: Although this gene has not been associated with a phenotype in OMIM nor Gen2Phen, an animal model and two population studies indicate that deletion or the minor alleles of rs4986790 or rs4986791 are all associated with susceptibility to respiratory syncytial virus (RSV). The recently published article speculates that TLR4 could be involved in recognizing SARS‐CoV‐2 and proposes the selective targeting of TLR4‐spike protein interaction to treat COVID‐19 (PMID 32383269).
COVID-19 research v0.362 TLR4 Sarah Leigh changed review comment from: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T399I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for p.D299G and p.T399I compared with control frequencies of 10.5% and 6.5%, respectively.; to: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T399I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for p.D299G and p.T399I compared with control frequencies of 10.5% and 6.5%, respectively.

PMID 32383269 reports that: cell surface TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 and speculates that selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19.
COVID-19 research v0.362 TNFSF4 Sarah Leigh Classified gene: TNFSF4 as Red List (low evidence)
COVID-19 research v0.362 TNFSF4 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or in Gen2Phen.
COVID-19 research v0.362 TNFSF4 Sarah Leigh Gene: tnfsf4 has been classified as Red List (Low Evidence).
COVID-19 research v0.361 TNFSF4 Sarah Leigh commented on gene: TNFSF4
COVID-19 research v0.361 TNFSF4 Sarah Leigh Publications for gene: TNFSF4 were set to 7913952; 8076595
COVID-19 research v0.360 FEZ1 Catherine Snow reviewed gene: FEZ1: Rating: ; Mode of pathogenicity: None; Publications: 31422020, 30815230; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.360 TNFSF4 Sarah Leigh Publications for gene: TNFSF4 were set to
COVID-19 research v0.359 TNFSF10 Rebecca Foulger Publications for gene: TNFSF10 were set to
COVID-19 research v0.358 TLR4 Sarah Leigh Phenotypes for gene: TLR4 were changed from to Susceptibility to respiratory syncytial virus
COVID-19 research v0.357 TLR4 Sarah Leigh Publications for gene: TLR4 were set to
COVID-19 research v0.356 TLR5 Sarah Leigh Publications for gene: TLR5 were set to
COVID-19 research v0.355 TLR5 Sarah Leigh edited their review of gene: TLR5: Added comment: TLR5 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
The transmembrane protein TLR5 is a component of the immune system that is highly expressed in intestinal mucosa and recognizes bacterial flagellin (PMID 20203013)(reviewed by Alison Coffey and team, Illumina).
PMID 25395539 reports that mice treated with bacterial flagellin prevented rotavirus (RV) infection and cured chronically RV-infections. This processed required the flagellin receptors Tlr5 and Nlrc4. Flagellin-induced activation of Tlr5 on dendritic cells elicited production of the cytokine Il22, resulting in a protective gene expression program in intestinal epithelial cells. Administration of Il22 to mice reproduced the capacity of flagellin to prevent or cure RV. It was proposed that activation of innate immunity with flagellin, via Tlr5 inducing IL22 could be useful in preventing or curing viral infections.; Changed publications: 20203013, 25395539
COVID-19 research v0.355 FCMR Catherine Snow Publications for gene: FCMR were set to
COVID-19 research v0.354 TLR5 Sarah Leigh Classified gene: TLR5 as Red List (low evidence)
COVID-19 research v0.354 TLR5 Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. However, there is evidence that this gene is associated with the immune response to viral infection (PMID 25395539).
COVID-19 research v0.354 TLR5 Sarah Leigh Gene: tlr5 has been classified as Red List (Low Evidence).
COVID-19 research v0.353 FCMR Catherine Snow reviewed gene: FCMR: Rating: ; Mode of pathogenicity: None; Publications: 32073687, 29461978, 28747342, 23359703; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.353 IRF5 Rebecca Foulger Classified gene: IRF5 as Green List (high evidence)
COVID-19 research v0.353 IRF5 Rebecca Foulger Gene: irf5 has been classified as Green List (High Evidence).
COVID-19 research v0.352 IRF5 Rebecca Foulger commented on gene: IRF5
COVID-19 research v0.352 IRF5 Rebecca Foulger gene: IRF5 was added
gene: IRF5 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: IRF5 was set to Unknown
COVID-19 research v0.351 TLR4 Sarah Leigh changed review comment from: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T359I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for D299G and T399I compared with control frequencies of 10.5% and 6.5%, respectively.; to: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T399I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for p.D299G and p.T399I compared with control frequencies of 10.5% and 6.5%, respectively.
COVID-19 research v0.351 TLR4 Sarah Leigh changed review comment from: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T359I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for D299G and T399I compared with control frequencies of 10.5% and 6.5%, respectively.; to: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T359I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the same minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for D299G and T399I compared with control frequencies of 10.5% and 6.5%, respectively.
COVID-19 research v0.351 EIF3M Catherine Snow Publications for gene: EIF3M were set to
COVID-19 research v0.350 EIF3M Catherine Snow reviewed gene: EIF3M: Rating: ; Mode of pathogenicity: None; Publications: 20676407, 15919898; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.350 TLR4 Sarah Leigh changed review comment from: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses.
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T359I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for D299G and T399I compared with control frequencies of 10.5% and 6.5%, respectively.; to: TLR4 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping).
PMID 1106249 found that proinflammatory cytokine responses to respiratory syncytial virus (RSV) F protein were reduced in mice with deletions of Tlr4. The lungs of Tlr4 -/- mice had high levels of infectious virus and were either unable to clear the virus or took longer to clear it, in comparison with wt mice. Suggesting that TLR4 is involved in innate immune responses to viruses (reviewed by Alison Coffey and team, Illumina).
PMID 17579031 showed that: production of IL8, IL6, and other cytokines in response to RSV was reduced in bronchial epithelial cells transfected with TLR4 constructs containing rs4986790 p.D299G or rs4986791 p.T359I, compared with cells expressing TLR4 with major alleles. The authors suggest that these variants compromise the first-line defense against RSV and confer increased susceptibility to severe bronchiolitis after RSV infection.
PMID 17709532 also found that the minor alleles were assosiated with symptomatic RSV disease in a mostly premature population, with 89.5% and 87.6% of patients being heterozygous for D299G and T399I compared with control frequencies of 10.5% and 6.5%, respectively.
COVID-19 research v0.350 TLR4 Sarah Leigh Classified gene: TLR4 as Green List (high evidence)
COVID-19 research v0.350 TLR4 Sarah Leigh Added comment: Comment on list classification: Although this gene has not been associated with a phenotype in OMIM nor Gen2Phen, an animal model and two population studies indicate that deletion or the minor alleles of rs4986790 or rs4986791 are all associated with susceptibility to respiratory syncytial virus (RSV).
COVID-19 research v0.350 TLR4 Sarah Leigh Gene: tlr4 has been classified as Green List (High Evidence).
COVID-19 research v0.349 HDAC6 Rebecca Foulger commented on gene: HDAC6: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): Histone deacetylase 6 (HDAC6) is a unique cytoplasmic deacetylase that regulates various important biological processes by preventing protein aggregation and deacetylating different non-histone substrates. Growing evidence has indicated a dual role for HDAC6 in viral infection and pathogenesis: HDAC6 may represent a host defence mechanism against viral infection by modulating microtubule acetylation, triggering antiviral immune response and stimulating protective autophagy, or it may be hijacked by the virus to enhance proinflammatory response (Zheng et al, 2017). HDAC6 promotes the aggresome/autophagic degradation of the viral polyprotein Pr55Gag to inhibit HIV-1 production and infection (Hernández et al, 2019). Depletion of HDAC6 expression (in vitro) led to impaired antiviral responses against RNA viruses, but not against DNA viruses. HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wildtype mice (Choi et al, 2016). Overexpression of Hdac6 enhances resistance to virus infection in embryonic stem cells and in mice (Wang et al, 2015).

Literature:
PMID: 27959772 - Zheng et al. (2017) (Review) This review highlights current data illustrating the complexity and importance of HDAC6 in viral pathogenesis.
HDAC6 has both proviral and antiviral effects. HDAC6 can inhibit infection of both RNA and DNA virus by modulating microtubule (MT) cytoskeleton and stimulating selective autophagy and restrict viral diffusion by triggering antiviral immune response. However, RNA viruses can also utilize HDAC6-mediated aggresome pathway or proinflammatory response to facilitate viral pathogenesis (Fig 1 and Table 1)
• HDAC6 triggers antiviral gene expression upon RNA virus infection (Fig 3a)
• HDAC6 interacts with Vif or A3G and competes for Vif–A3G interaction through its BUZ domain, impairs the incorporation of Vif into nascent virions and finally controls HIV-1 infectiveness (Fig 4)
• HDAC6 facilitates viral uncoating and pathogenesis (Fig 5)
Findings support exploration of a potential therapeutic role for restricting viral pathogenesis by targeting HDAC6.

PMID: 31736889: Hernández et al. (2019) - HIV Nef is a central auxiliary protein in HIV infection and pathogenesis. Results from the study indicate that HDAC6 promotes the aggresome/autophagic degradation of the viral polyprotein Pr55Gag to inhibit HIV-1 production
• HIV-1 Nef viral protein induces HDAC6 Degradation (Enzyme degradation by recombinant HIV-1 Nef in HEK-293T cells in both endogenous and over expressed HDAC6 is shown in Fig 1)
• Mutated Nef protein Nef-PPAA did not promote HDAC6 degradation (Figure 3A, quantified in Figure 3B). This fact may indicate that this motif is involved in Nef-mediated HDAC6 interaction and/or processing, or that a conformational change in the mutated viral protein abrogates the degradative activity observed with the wt-Nef (Figures 1–3)
• Nef assures viral production and infection by targeting HDAC6, stabilizing Pr55Gag and Vif, thereby facilitating Pr55Gag location and aggregation at plasma membrane, and subsequent virus production and infection capacity (events summarized by schematic illustrations in Figure 10)

PMID: 26746851: Choi et al. (2016) - HDAC6 plays an important role in the antiviral immune response by producing IFNs and proinflammatory cytokines in responses to foreign RNA viruses.
HDAC6+/+ and HDAC6-/- mice were intravenously infected with vesicular stomatitis virus (VSV, Indiana strain). Results show that
• HDAC6-/- mice are more susceptible to VSV-Indiana infection than HDAC6+/+ mice and showed significantly decreased survival rate (Fig 1A)
• Virus titers were significantly higher and IFN-b and IL-6 production was markedly lower in HDAC6-/- mice than in HDAC6+/+ mice (Fig 1D and E)
• Role of HDAC6 in cytokine induction by poly(I:C), which is a synthetic double-stranded RNA (dsRNA): Intravenous injection of poly(I:C) caused the rapid and robust induction of IFN-b and IL-6 in HDAC6+/+ mice; however, induction of these cytokines was significantly reduced in HDAC6-/-mice (Fig 1F).
In vitro
• HDAC6 deficiency reduces the innate immune response on mouse macrophage and mouse embryonic fibroblast (Fig 3)
• HDAC6 and RIG-I transiently interact in response to RNA viral infection (Fig 5A and B) and HDAC6 regulates the binding of RIG-I to 50 pppdsRNA by deacetylating RIG-I (Fig 5G)

PMID: 25482409 Wang et al. (2015) - This is another study that provides a proof of principle of antivirus function by Hdac6 in vivo. HDAC6 overexpression significantly enhances resistance to avian H5N1 virus infection and extends the survival rate in Hdac6tg mice (transgenic) (Fig 2). Also, ES cells overexpressing Hdac6 displayed resistance to infection by adenovirus at high titers (Fig 1).
COVID-19 research v0.349 DAG1 Rebecca Foulger commented on gene: DAG1: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): The DAG1 gene encodes 2 dystroglycan proteins, both of which are dystrophin-associated glycoproteins (DAGs) (OMIM:128239). Alpha-Dystroglycan (a-DG) is a common receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses including the human pathogenic Lassa fever virus (Imperiali et al. 2005; Kunz et al. 2009; Rojek et al. 2007).

PubMed 16254364: Imperiali et al. (2005) - alpha-Dystroglycan (a-DG) was identified as a common receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses including the human pathogenic Lassa fever virus. Arenaviruses are enveloped, single-stranded RNA viruses with a bisegmented ambisense genome. Susceptibility toward LCMV infection differed in various cell lines despite them expressing comparable levels of DG, suggesting that posttranslational modifications of a-DG would be involved in viral receptor function. Demonstrated that glycosylation of a-DG, and in particular, O mannosylation, which is a rare type of O-linked glycosylation in mammals, is essential for LCMV receptor function. Cells that are defective in components of the O-mannosylation pathway showed strikingly reduced LCMV infectibility. As defective O mannosylation is associated with severe clinical symptoms in mammals such as congenital muscular dystrophies, it is likely that LCMV and potentially other arenaviruses may have selected this conserved and crucial posttranslational modification as the primary target structure for cell entry and infection.

PMID 19324387: Kunz et al. (2009) - Old World arenaviruses LCMV (lymphocytic choriomeningitis virus) and LASV (Lassa virus) enter the host cell predominantly via a novel and unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Infection of cells with LCMV and LASV depends on DG, this unusual endocytotic pathway could be related to normal cellular trafficking of the DG complex. Arenavirus particles may target DG for an endocytotic pathway not normally used in uninfected cells thereby inducing an entry route specifically tailored to the pathogen's needs.

PMID 17360738: Rojek et al. (2007) - Found that protein O mannosylation of α-DG is crucial for the binding of arenaviruses of distinct phylogenetic origins, including LFV, Mobala virus, and clade C New World arenaviruses.
Observed that overexpression of LARGE in cells deficient in O mannosylation resulted in highly glycosylated α-DG that was functional as a receptor for arenaviruses. Demonstrate that arenaviruses recognize the same highly conserved O-glycan structures on α-DG involved in ECM protein binding, indicating a strikingly similar mechanism of receptor recognition by pathogen- and host-derived ligands.

PMID 21185048: Oldstone et al. (2011) - Dendritic cells (DC)s express the highest levels of α-DG and are the sentinel cells that LCMV, and presumably also LFV, infect. The resultant infection of DCs compromises DC function.
Determinant of injury is the displacement of laminin or other ECM molecules that bind to the same site on α-DG that LCMV and LFV seek. When ECM molecules are pushed aside, the virus destabilizes membranes and causes interference with ECM signals that are required to maintain homeostasis.

PMID 15857984: Kunz et al. (2005)
Show that LFV (Lassa fever virus) binds to α-DG with high affinity in the low-nanomolar range.
Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on α-DG for infection of cells.
LFV was found to efficiently compete with laminin α1 and α2 chains for α-DG binding.
LCMV uses the same domains of α-DG for binding that are used in LFV binding.
Findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates.
COVID-19 research v0.349 BECN1 Rebecca Foulger commented on gene: BECN1: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): BECN1 encodes the beclin1 protein which is an established regulator of the autophagic pathway. Autophagy is a key mechanism against invading bacteria, parasites, and viruses in innate immune cells including monocytes/macrophages, dendritic cells and neutrophils (reviewed in Tao et al. 2020). Viral proteins such as HIV-1 Nef, ICP34.5 of HSV-1 and M11 of MHV-68 have been shown to interact with Beclin-1 and block the late stage of autophagy, thereby protecting viral particles from degradation (Kyei et al 2009; Orvedahl et al. (2007); Ku et al. (2008)

PMID:32265919 Tao et al. 2020 (review) - Autophagy is a key mechanism against invading bacteria, parasites, and viruses in innate immune cells including monocytes/macrophages, dendritic cells (conventional dendritic cells-cDCs and plasmacytoid dendritic cells-pDCs) and neutrophils. BECN1 encodes beclin1 protein which is an established regulator of the autophagic pathway. Viral proteins may target BECN1 to inhibit autophagy.

PMID: 19635843 Kyei et al. (2009) - A series of experiments showed that the Nef protein of HIV inhibits the autophagic maturation pathway (fig 5). Macrophages transfected with Nef-GFP showed colocalization of Nef with Beclin-1 and the two proteins were shown to physically interact in immunoprecipitation experiments (Fig6).

PMID: 18248095 Ku et al. (2008) - In NIH3T3 cell culture studies, the M11, a viral BCL-2 of murine gamma herpesvirus 68 was shown to bind Beclin-1 and to inhibit to inhibit Beclin-1 mediated autophagy (Fig 4).

PMID: 18005679 Orvedahl et al. (2007) - The authors used coimmunoprecipitation experiments in both HEK293 cells and embryonic stem cells to show that the neurovirulence protein of Herpes simplex virus (HSV)-1, ICP34.5, binds to the C terminus of BECN1 (Fig 2). In MCF7 stably expressing BECN1cells, transfection of the ICP34.5 inhibited autophagy (Fig 2). Mutant HSV-1 lacking the ICP34.5 BECN1-binding domain failed to inhibit autophagy in primary sympathetic neurons (Fig 5A) and had impaired ability to cause lethal encephalitis in mice (Fig 6) .
COVID-19 research v0.349 CXCL8 Rebecca Foulger commented on gene: CXCL8: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor):

• CXCL8 is a proinflammatory chemokine that plays a role in inflammatory response and immune cell trafficking
• Multiple studies show IL-8 levels were shown to be elevated in plasma of patients with COVID-19, SARS-CoV, or MERS-CoV compared to controls. These include a number of recent COVID-19 studies (Coperchini et al. 2020).
• Higher levels were detected in more severe cases (Gong et al. 2020; Qin et al. 2020; Yan et al. 2020), although one study shows the levels are within the normal range (Qin et al. 2020)
• Gong et al. (2020) suggest that IL-8 might be a therapeutic target COVID-19

Literature:
PMID 32446778; Coperchini et al. (2020)
• Review article describing the involvement of chemokine/chemokine-receptor system in COVID-19
• Discusses the concept of cytokine storm where the immune system is ‘attacking’ the body resulting in acute respiratory distress syndrome.
• Multiple studies are mentioned that show high levels of CXCL8 in the plasma and broncho-alveolar fluid in patients with acute respiratory distress syndrome. Reference a paper that notes that pre-treatment with an anti-CXCL8 antibody prevented acute lung injury that generally develops.
• In vivo studies showed elevated CXCL8 in patients with SARS-CoV.
• In vitro studies where peripheral blood mononuclear cells from healthy donor inoculated with SARS-CoV showed enhancement in the expression of CXCL8
• Similarly, CXCL8 was upregulated in cells lysates when with MERS-CoV infection of polarized airway epithelial cells (higher expression than SARS-CoV).
• Higher plasma levels of CXCL8 in patients with COVID-19 compared to healthy controls; however, transcription of CSCL8 was not upregulated

MedRxiv; Gong et al. (2020)
• Evaluated disease severity in a total of 100 patients with COVID-19 pneumonia
• CXCL8 (IL-8 in this paper) was detected in these patients and IL-8 levels were shown to be associated with disease severity (P<0.001); significant differences were noted between critical and severe patients or critical and mild groups (Tables 2 and 3)
• Suggest that IL-8 might be a therapeutic target COVID-19

PMID 32161940; Qin et al. (2020)
• Retrospective study of 452 patients with COVID-19; severity of COVID-19 defined according to the Fifth Revised Trial Version of the Novel Coronavirus Pneumonia Diagnosis and Treatment Guidance
• Clinical and laboratory data were collected
• A majority of the severe cases (n=286) had elevated levels of IL-8 (18.4 pg/mL vs 13.7 pg/mL, respectively; p<0.001) compared to the nonsevere cases (n=166), although they were all in the normal (0-62.0 pg/mL) (Table 2)

MedRxiv; Yan et al. (2020)
• Identified 25 genes that showed highly conserved kinetics in COVID-19 patients
• Figure 3F shows expression of CXCL8 and plasma levels of IL-8 from four individuals with COVID-19 compared to four healthy controls was higher in patients especially in the severe stage (p<0.001)

PMID 15585888; Chang et al. (2004)
• Introduction has a summary of previously published papers and notes that high serum levels of IL-8 were detected during acute phase and associated with lung lesions in patients with SARS in one study. Another study suggests use of corticosteroids in reducing pulmonary inflammation due to IL-8.

• Chang et al. (2004) used transient transfection of the SARS-CoV S protein-encoding plasmid on the IL-8 promoter. Measure of IL-8 release in lung cells showed an upregulation of IL-8 release. In addition, a specific region of the S protein was identified as a potentially important region for inducing IL-8 release.

There are additional case-control studies suggesting possible association of polymorphisms in CXCL8 and acute bronchiolitis susceptibility (Pinto et al. 2017; PMID 27890033), asthma (Charrad et al. 2017; PMID 28993876), or human papillomavirus infection (weaker evidence; Junior et al. 2016; PMID 27783717).
COVID-19 research v0.349 TLR4 Sarah Leigh reviewed gene: TLR4: Rating: ; Mode of pathogenicity: None; Publications: 11062499, 17579031, 17709532; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.349 VPS11 Rebecca Foulger commented on gene: VPS11: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): The VPS11 gene encodes a protein which is part of the homotypic fusion and vacuole protein-sorting (HOPS) complex that mediates fusion of endosome and lysosomes; VPS11 is involved in late-stage endosome to lysosome maturation. In HAP1 cells mutagenized with a retroviral gene-trap vector, mutations in VSP11 were enriched in Ebola virus-resistant cells. In addition, VPS11-deficient cells showed resistance to Ebola and Marburg virus compared to controls. Escape of the Ebola virus to the cytoplasm was blocked in VPS11-deficient cells (Carette et al. 2011). In HeLa cells RNAi downregulation of VPS11 showed decreased relative percentage infection with mouse hepatitis coronavirus (MHV) and feline infectious peritonitis virus, with a larger effect for MHV (Burkard et al. 2014). Similarly, in HEK293 cells, luciferase activity of Ebola virus and SARS-CoV-S were reduced in siRNA downregulated VPS11 cells (Zhou et al. 2016).

PMID 21866103; Carette et al. (2011) - Used retroviral gene-trap vector to mutagenize HAP1 cells. Identified genes enriched for mutations in vesicular stomatitis virus bearing the EboV glycoprotein (rVSV-GP-EboV)-resistant cells. Enriched for mutations in VPS11 as well as other subunits of the HOPS complex (six subunits including VPS11), which mediates fusion of endosome and lysosomes; VPS11 is involved in late-stage endosome to lysosome maturation. In addition, VPS11-deficient cells (using gene-trap insertions) showed resistance to infection with Marburg virus or Ebola virus (Figures 1C and Figure S4C) compared to controls. Ebola virus escape to the cytoplasm is blocked in VPS11-deficient cells compared to WT (Figure 3D)

PMID 25375324; Burkard et al. (2014) - Evaluated entry of mouse hepatitis coronavirus (MHV) in HeLa cells with GFP-expressing MHV RNAi mediated downregulation of VPS11 (using three different siRNAs) showed the percentage of relative infection was reduced compared to negative siRNA controls (Figure 1C). Luciferase expressing feline infectious peritonitis virus (FIPV) was also evaluated in HeLa cells and RNAi mediated downregulation of VPS11 showed reduced relative infection for two of three siRNAs compared to negative siRNA controls (Figure 10)

PMID 26953343; Zhou et al. (2016) - Study to evaluate effects of antibiotics on proteins involved in virus entry. SiRNA-mediated knockdown of VSP11 expression showed decreased relative luciferase activity in HEK293 cells infected with Ebola virus or SARS-CoV-S, but not with vesicular stomatitis virus. In addition, treatment with the glycopeptide antibiotic teicoplanin did not show an effect on the HOPS complex
COVID-19 research v0.349 RNASEL Rebecca Foulger commented on gene: RNASEL: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): RNASEL, also known as 2-5A-dependent RNase is a component of the interferon-regulated 2-5A system that functions in the antiviral interferon pathway. Treatment of cells with interferon results in enhanced levels of both 2-5A-dependent RNase and a group of synthetases that produce 5-prime-triphosphorylated, 2-prime,5-prime-oligoadenylates (2-5A) from ATP. The role of the 2-5A system in the control of viral and cellular growth suggests that defects in the 2-5A-dependent RNase gene could result in reduced immunity to virus infections and cancer (Hassel et al., 1993). Several studies aiming to identify a genetic association between RNASEL and viral susceptibility have failed to identified statistically significant SNPs (Yakub et al. 2005; Arredondo et al. 2012). However, there is sufficient experimental evidence, including a mouse model and in-vitro studies that RNASEL is an important contributor in host defence against several viruses (Gusho et al. 2016 (review); Zhou et al. 1997; Panda et al. 2019).

PMID 27595182: Gusho et al. 2016 (review) - RNase L is a unique IFN-regulated endoribonuclease that serves as an important mediator of antiviral innate immunity with possible roles in antibacterial defense and prostate cancer. It is controlled by IFN-inducible oligo-adenylate synthetases (OASs) and double-stranded RNAs (dsRNAs). OAS-RNase L (Fig. 1) pathway, discovered in the mid-1970s, was one of the first IFN-dependent antiviral pathways to be characterized. OASs are IFN-I/-III-inducible genes that are expressed at very low basal levels in many cell types. OASs1-3 act as pathogen recognition receptors that sense dsRNAs and activate the synthesis of 5’-phosphorylated 2’-5’ linked oligoadenylates from ATP (2-5A). 2-5A acts as a second messenger and binds monomeric RNase L, and activates its dimer formation. Active RNase L cleaves cellular and viral RNAs within single-stranded regions. RNA degradation directly and indirectly activates subsequent events, including the elimination of viral genomes, inhibition of cellular and viral protein synthesis; and activation of several cellular signaling pathways, including those involved in autophagy, apoptosis, senescence, IFN-b production, and NLRP3-inflammasome activation as part of its antiviral mechanism (references provided). Authors state that many viruses have evolved or acquired strategies that antagonize the OAS-RNase L pathway to evade antiviral innate immunity. Some, such as Influenza A (IAV), HSV and Vaccinia virus act through an RNA-binding domain which binds to and sequesters dsRNA, the activator of OAS. Others bind directly to monomeric RNase L preventing it from activation by dimerization. Some coronaviruses (MERS-CoV and MHV) are described to act through their ns-domains with 2’-5’ PDE activity that degrades 2-5A and thus prevent activation of RNase L.

Some additional evidence of interest:
-OAS3 was shown to exert antiviral activity against Dengue virus in an RNase L-dependent manner, indicating that OAS3 synthesizes active 2-5A in sufficient amounts for RNase L activation
-RNase L activation by dsRNA signaling or viral infection contributes to IFN-b production, indicating its important role in innate immunity. The ribonuclease function of RNase L is essential for its effect on IFN-b production
-Moreover, mice deficient in RNase L had several-fold reduced levels of IFN-b induction after infection with RNA viruses (EMCV and Sendai virus)
-Stable expression of wild-type human full-length RNase L, but not ribonuclease dead mutant (R667A), activates IL-1b and caspase 1 secretion in RNase L-deficient THP1 cells after virus infection or 2-5A transfection

PMID 9351818: Zhou et al. (1997) RNASEL Mouse model
To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon was impaired in RNaseL–/– mice providing the first evidence that the 2-5A system functions as an antiviral pathway in animals. Authors showed that EMCV replicates more efficiently in cells lacking RNase L than in wild type cells, even after interferon treatment, although the effect is relatively small. Next, authors determined that survival of RNaseL-/- mice after EMCV infection was significantly reduced both in presence and absence of IF (Fig 3). Enlarged thymus and reduced level of apoptosis in thymus and spleen were also found (Fig 4-5).

PMID 31156620 Panda et al (2019)
Interferon regulatory factor-1 (IRF1) regulates expression of RNaseL and knockdown of RNaseL in BEAS-2B cells resulted in significantly increased VSV infection rates. (Fig.6)

PMID 22356654 Arredondo et al. 2012
Authors studied allelic variants in RNASEL gene at codon 462 (R462Q, rs486907) for susceptibility to viral infection, prostate cancer and chronic fatigue syndrome. The allelic distribution at codon 462 was 139 (33.9%), 204 (49.8%), and 67 (16.3%) for RR, RQ, and QQ, respectively, in 410 individuals in Spain. There were no significant differences comparing 105 blood donors and 71 patients with HIV-1 infection, 27 with chronic hepatitis C, 67 with prostate cancer, and 107 with chronic fatigue syndrome. In contrast, two-thirds of 18 patients with HTLV-1 infection and 15 with chronic hepatitis B harbored RR (Table 1). Thus, polymorphisms at the RNASEL gene do not seem to influence the susceptibility to common viral infections or conditions potentially of viral etiology. They conclude that the role in influencing the susceptibility to HTLV-1 or HBV chronic infection warrants further examination in larger patient populations.
COVID-19 research v0.349 PVR Rebecca Foulger commented on gene: PVR: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): PVR, or CD155, belongs to a large family of immunoglobulin (Ig)-like molecules called nectins and nectin-like proteins, which mediate cell-cell adhesion, cell migration, and cell polarization through interaction with other nectins. It is both a viral receptor and immunomodulatory protein and is involved in many biological processes. PVR serves as the entry receptor for poliovirus and thereby is responsible for human susceptibility to poliovirus infection. Susceptibility to poliovirus is a function of the presence or absence of the cellular receptor to which the virus binds as the first step in poliovirus replication. Mendelsohn et al. (1986) succeeded in transforming a human poliovirus receptor gene into mouse L cells, which are ordinarily resistant to poliovirus infection because they do not bear a poliovirus receptor. Monoclonal antibody directed against the HeLa cell poliovirus receptor site was used in rosette assays to identify poliovirus-sensitive transformants. Evidence for PVR as a Viral Receptor, regulator of immune function and its role in cancer is described in Bowers et al (2017). CD155-deficient mice develop normally without displaying an overt phenotype. However, the animals are distinguished by distinct deficits in the development of a regular humoral immune response (Maier et al, 2007)

Literature:
PMID: 28870470 - Bowers et al, 2017 (Review) - PVR is an important cell adhesion protein and is involved in the transendothelial migration of leukocytes. PVR undergoes alternative splicing, generating 4 unique splice forms. Protein isoforms and interactions with Poliovirus are summarized in Table 1. In addition to its role as a receptor for the human poliovirus, several native biological functions have also been uncovered. PVR is an important cell adhesion protein and is involved in the transendothelial migration of leukocytes. Through its interactions with CD226 and TIGIT, transmembrane proteins found on leukocytes, PVR is a key regulator of the cell-mediated immune response. In this review more evidence is available for PVR as a Viral Receptor and PVR as a regulator of immune function

PMID: 25113908 - Bolduan et al, 2014 - NL4-3 Vpu protein from HIV downregulates the activating NK cell receptor CD155 from the cell surface by the conserved alanine residues Ala-10, Ala-14 and Ala-18 of its TM domain to evade NK cell mediated immune response against HIV-1 infected cells (Hela cells)
PMID: 19815499 - Stanietsky et al, 2009 - TIGIT (a protein expressed by all human NK cells) binds PVR and PVRL2 but not PVRL3 and inhibits NK cytotoxicity directly through its ITIM.

PMID: 12943679 - Baury et al, 2003 -As the extracellular domains of the sPVR (soluble PVR) isoforms are identical to the extracellular domain of transmembrane PVR, they can compete with transmembrane PVR for the canyon-like receptor binding site of poliovirus. When sPVR is overexpressed in poliovirus susceptible HeLa cells, it significantly reduces viral entry and viral infectivity

PMID: 17621371 - Maier et al, 2007 - In this study, Maier et al explore the expression profile of CD155 on murine hematopoietic cells utilizing newly generated mAb. They report on the establishment and immunological analysis of mice deficient in CD155. CD155-deficient mice (knock out) develop normally without displaying an overt phenotype. However, the animals are distinguished by distinct deficits in the development of a regular humoral immune response. Whereas systemic challenges revealed no differences, orally administered antigen evoked less efficient IgG and IgA antibody responses (Figure 7) despite of normal IgM titers when compared to wild-type mice. Therefore, CD155 may assist in an efficient humoral immune response generated within the intestinal immune system.

PMID: 28800489 - Lin et al, 2017 - Amino acid changes in the C’C”D region in poliovirus receptor domain 1 disrupt poliovirus binding. We substituted this region of Pvr into the corresponding region of a murine homolog, nectin-2. The chimeric receptor, nectin-2Pvr(c'c"d), rendered transformed L cells susceptible to infection with poliovirus P1/Mahoney, but not with polioviruses P2/ Lansing and P3/Leon, due to lack of binding.

PMID: 2597248 - Kanemaru et al, 2015 - Mice genetically deficient in CD155 or treated with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T cell differentiation and allergic diseases.
COVID-19 research v0.349 EGFR Catherine Snow Publications for gene: EGFR were set to
COVID-19 research v0.348 EGFR Catherine Snow reviewed gene: EGFR: Rating: ; Mode of pathogenicity: None; Publications: 28390872, 31616667, 8523580, 28404843, 20844577; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.348 PTX3 Rebecca Foulger commented on gene: PTX3: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): Pentraxins are a superfamily of conserved humoral mediators of innate immunity. PTX3, the prototypic long pentraxin, is a soluble pattern recognition molecule produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. It is involved in the initiation of protective responses against select pathogens, acting as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. It is an established biomarker in sepsis, with PTX3 plasma levels associated with severity of the condition, patient survival, and response to therapy.

PTX3 has been characterized as a biomarker of severity and outcomes in different infections caused by bacteria, fungi or viruses. Patients with pulmonary aspergillosis, tuberculosis, dengue virus infection, meningococcal disease leptospirosis and shigellosis have increased PTX3 plasma levels that correlate with disease severity and could act as predictor of unfavourable outcomes (PMID 31031772: Porte et al. 2019). Several studies using Ptx3-deficient mice showed an increased susceptibility to fungal, bacterial and viral pathogens (Porte et al. 2019). In contrast, a study in PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication (Foo et al. 2015). PTX3 administration has shown to be protective also against infections with Influenza virus, murine cytomegalovirus, Neisseria meningitidis, and P. aeruginosa in neonates and during chronic infections by reducing viral load and inflammatory pathology. (PMID 31031772: Porte et al. 2019, PMD 18292565: Reading et al. 2008).

PMID: 25695775: Foo et al. (2015) - Found that pentraxin 3 (PTX3) was highly expressed in chikungunya virus (CHIKV) and Ross River virus (RRV) patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication.

PMID: 18292565 - Reading et al. (2008) - Identified the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model found PTX3 to be rapidly induced following influenza infection and that PTX3-/- mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses.

PMID 19968561: Bottazzi et al. (2010) (Review) - PTX3 binds to human and murine cytomegalovirus and influenza virus type A (IVA). The interaction between PTX3 and IVA occurs through binding of sialylated ligands on PTX3 to the viral hemagglutinin and results in neutralization of virus infectivity in vitro. Consistently, desialylated PTX3 does not bind IVA and does not neutralize virus infectivity.
COVID-19 research v0.348 NPC1 Rebecca Foulger commented on gene: NPC1: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): NPC1 encodes a polytopic protein that resides in the limiting membrane of late endosomes and lysosomes (LE/LY) and mediates distribution of lipoprotein-derived cholesterol in cells (Cote et al. (2011). NPC1 expression is critical for filovirus infection (EboV and MarV) and the mechanism of infection is not dependent on NPC1 cholesterol transport activity (Carette et al. 2011). Structural studies demonstrate that the C-domain of NPC1 binds to the primed EBOV glycoprotein (Wang et al. 2016; Gong et al. 2016).

PMID 21866103: Carette et al. (2011)
Genome-wide haploid genetic screen was performed in primary fibroblasts derived from human Niemann-Pick type C1 disease patients to identify host factors required for Filovirus infection. These cells are resistant to infection by EboV and MarV but remain fully susceptible to other unrelated viruses (Figure 2A, B). Resistance of NPC1-deficient cells was not caused by cholesterol transport defects (Fig S8). Infection in these cells was restored by expression of wild type NPC1 (Figure 2C). Similar results were observed in NPC1-null Chinese hamster ovary (CHO) cells, with loss of NPC1 conferring complete resistance to viral infection (Figure S6D) that was reversed by expression of human NPC1 (Figure S6E). Electron micrographs of NPC1 mutant cells infected with rVSV-GP-EboV indicate that NPC1 is required in downstream process in filovirus entry leading to viral membrane fusion and escape from the lysosomal compartment. Knockdown of NPC1 in HUVEC diminished infection by filoviruses (Figure 4D and S18) suggesting that NPC1 is critical for authentic filovirus infection. Furthermore, NPC1+/+ mice rapidly succumb to infection with either filovirus while NPC1−/+ mice were largely protected (Figure 4E).

PMID 2186610: Cote et al. (2011)
HeLa cells treated with benzylpiperazine adamantane diamide-derived compounds (3.0 and 3.47) developed cytoplasmic vacuoles indicating that that they target one or more proteins involved in regulation of cholesterol uptake in cells. CHO cells lacking NPC1 were completely resistant to infection by this virus and infection of these cells was fully restored when NPC1 was expressed. NPC1 expression but not NPC1-dependent cholesterol transport activity is essential for EboV infection (Fig 2c). 3.0-derived compounds inhibit EboV infection by interfering with binding of cleaved glycoprotein to NPC1 (Fig 4).

PMID 26771495: Wang et al. (2016)
The crystal structure of the primed glycoprotein (GPcl) of Ebola virus and domain C of NPC1 (NPC1-C) demonstrates that the NPC1-C binds to the primed EBOV GP (Fig 1, 3). Further, it suggests that a membrane-fusion-priming conformational change occurs in GPcl or the binding of GPcl, and this is a unique feature for all the filoviruses. NPC1-interacting compound 3.47 competitively blocks the primed GP binding to the membrane probably binds to the two protruding loops of NPC1-C. Compound U18666A binds to a different site on NPC1 causing endosomal calcium depletion. Furthermore, peptide inhibitors or small molecules, which can easily penetrate the cell membrane and reach the primed GP in the late endosomes could also act as potential therapeutic agents.

PMID 27238017: Gong et al. (2016)
Full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of EBOV was determined by single-particle electron cryomicroscopy. NPC1 contains 13 transmembrane segments (TMs) and three lumenal domains, A (NTD), C, and I. TMs 2–13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3–7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling. EBOV-GPcl binds to NPC1 through the domain C.
COVID-19 research v0.348 NECTIN1 Rebecca Foulger commented on gene: NECTIN1: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): Amino acid substitutions in nectin-1 showed impaired entry of Herpes simplex virus (HSV) into CHO-K1 cells (PMID:1175687;12072525). Nectin-1 knockout mice inoculated with HSV in the hippocampus demonstrated that nectin-1 is necessary for neurologic disease caused by HSV (PMID:19805039).

PMID 11756979 - Struyf et al. (2002) - Searched for polymorphisms in HVEM, nectin-1, and nectin-2 via sequencing in individuals shown to immune seronegative for herpes simplex virus (HSV). These individuals showed T cell responses to HSV antigens and did not have anti-HSV antibodies detected in their serum. There were three individuals that were immune seronegative, three with no signs of cellular or humoral immunity, and three with frequent reactivations of HSV who had antibody and T cell responses to HSV. One individual in the study (true seronegative as demonstrated by negative testing for HSV-1 and HSV-2 and no HSV-specific T cell immunity) was identified to have a variant in nectin-1 (c.752G>A, p.Arg199Gln) in addition to one missense variant in HVEM (table 2). This variant was screened for 644 healthy White individuals and 17 were shown to be heterozygous for the p.Arg199Gln variant and one individual had a different missense variant at the same residue. The p.Arg199Gln variant occurs in the first constant-like domain for the protein. A different domain, the N-terminal variable-like domain, has previously been shown as important for virus entry into the cell.

PMID 12072525 - Martinez and Spear (2002) - Investigated whether residues 75-77 and 85 of nectin-1 (homologous to regions A and B of nectin-2) are necessary for HSV-1 entry into CHO-K1 cells (which are resistant to the entry of alphaherpesviruses unless they are created to express a gD receptor). When there were mutants involving both residues 77 and 85, there was severely diminished ability of HSV-1 or HSV-2 to enter the cell and was unable to find to soluble forms of HSV-1 and HSV-2 (table 1; fig. 3). Note that these mutants allowed entry of PRV and BHV-1.

PMID 19805039 - Kopp et al. (2009) - Nectin-1 knockout (KO) mice were inoculated intracranially and into the hippocampus with herpes simplex virus (HSV) and infection of neurons compared to HVEM KO mice, HVEM/nectin-1 KO mice, and controls. Nectin-1 KO mice were resistant to disease, as were the double KO mice at doses of the virus up to 100x needed to cause disease as compared to the wildtype and HVEM KO mice (Fig. 1). Nectin-1 is necessary for neurologic disease caused by HSV. Viral antigen was not detected in brain sections from double KO mice, but could be detected for nectin-1 KO mice (limited regions), HVEM-KO mice and wildtype (more widespread) (Fig. 2A). HSV was shown to be located to the ventricular surfaces in nectin-1 KO mice and confirmed as non-parenchymal cells (Fig. 2B).
COVID-19 research v0.348 MIR155 Rebecca Foulger commented on gene: MIR155: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): MIR155 (also referred to as BIC) is an endogenous noncoding RNA involved in regulation of the immune response, in particular T-cell differentiation, and in regulation of innate immunity (PMID: 32233818; 217121651;1746328969;20852130). This miRNA has been associated with various virus infections (PMID: 32233818;28139244;23686237;26072128). miR-155-5p expression has been shown to be induced in mice infected with influenza A virus (PMID: 32308197 - in this study, lung injury by ARDS was attenuated by deletion of miR-155, making this miRNA a potential therapeutic target in the context of COVID-19). Through single cell and bulk RNA profiling of SARS-CoV-2 and SARS-CoV infections in three human cell lines (H1299, Caco-2 and Calu-3 cells), Emanuel et al. (2020) (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.05.079194) demonstrated strong expression of the immunity and inflammation-associated microRNA miRNA-155 upon viral infection with both viruses. Both viruses triggered a 16-fold upregulation of one form of miR-155 and a 3-fold upregulation of another.

A role for MIR155 in viral susceptibility for a range of viruses and the immune response has also been demonstrated in a series of mouse models:

PMID 23601686: In Mir155 -/- mice, Dudda et al. (2013) observed severely reduced accumulation of Cd8-positive T cells during acute and chronic viral infections with impaired control of viral replication. Lack of Mir155 led to an accumulation of Socs1 resulting in defective cytokine signaling through Stat5. Dudda et al. also concluded that MIR155 and its target, SOCS1, are key regulators of CD8-positive T cells.

PMID 23275599: Lind et al. (2013) found that mice lacking Mir155 had impaired Cd8 positive T-cell responses to infections with lymphocytic choriomeningitis virus and the intracellular bacteria Listeria monocytogenes and concluded that MIR155 is required for acute CD8-positive T-cell responses and proposed that targeting MIR155 may be useful in modulating immune responses.

PMID 24516198: Bhela et al. (2014) – 75 to 80% of MIR155 null mice infected ocularly with herpes simplex virus (HSV)-1 developed herpes simplex encephalitis with elevated viral titers in brain, but not in cornea. Immunohistochemical and flow cytometric analyses in Mir155-null mice showed diminished Cd8-positive T-cell numbers, functionality, and homing capacity. Adoptive transfer of HSV-1-immune Cd8-positive T cells to Mir155-null mice 24 hours after infection provided protection from HSE. The authors concluded that MIR155 deficiency results in enhanced susceptibility of the nervous system to HSV-1 infection.
COVID-19 research v0.348 KLF2 Rebecca Foulger commented on gene: KLF2: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): KLF2 is a member of the Kruppel-like factor (KLF) family of zinc finger transcription factors that function in cell differentiation, quiescence, and homeostasis. It also plays a regulatory role in inflammation-related pathways (Jha and Das 2017). Richardson et al. (2012) showed that KLF2 acts as a host factor that modulates CCR5 expression in CD4 T cells and influences susceptibility to infection with CCR5-dependent HIV-1 strains. Huang et al. (2017) showed through both network analyses and experimental results that KLF2 plays a central role in regulating many genes associated with acute respiratory distress syndrome (ARDS) identified by GWAS and that overexpression of KLF2 in vivo in mice could mitigate lung injury and expression of inflammatory genes, including that induced by influenza A virus.

PMID 17141159: Lee et al. (2006) - KLF2 deficient mice die in prenatal stage due to vascular defects, highlighting its crucial role in embryonic development. Lethal high-output heart failure, as found in the KO mice, was also observed in zebrafish embryos after morpholino inhibition of the Klf2 ortholog klf2a. CD4+ T cells from KLF2-deficient mice expressed multiple inflammatory chemokine receptors, suggesting that loss of KLF2 leads to redirection of naïve T cells to nonlymphoid sites (Sebzda et al., 2008).

PMID 19592277: Weinreich et al. (2009) - Demonstrated upregulation of the chemokine receptor CXCR3 on KLF2-deficient T cells (Fig. 1). KLF2-deficient T cells also overproduced IL-4 (Fig. 5).

PMID 22988032: Richardson et al. (2012) - Tested whether the abundance of KLF2 after T cell activation regulates CCR5 expression and, thus, susceptibility of a T cell to CCR5-dependent HIV-1 strains (R5). Introduced small interfering RNA targeting KLF2 expression and demonstrated that reduced KLF2 expression also resulted in less CCR5 (Fig. 3). Introduction of KLF2 under control of a heterologous promoter could restore CCR5 expression and R5 susceptibility to CD3/28 costimulated T cells and some transformed cell lines (Fig. 5, 6). KLF2 is a host factor that modulates CCR5 expression in CD4 T cells and influences susceptibility to R5 infection.

PMID 29125549: (review) Jha and Das (2017) - KLF2 also plays a critical regulatory role in various inflammatory diseases and their pathogenesis.

PMID 27855271: Huang et al. (2017) - Animal and in vitro models of acute lung injury were used to characterize KLF2 expression and its downstream effects responding to influenza A virus (A/WSN/33 [H1N1]), tumor necrosis factor-α, LPS, mechanical stretch/ventilation, or microvascular flow to examine the role of the gene in endothelial barrier disruption and cytokine storm in experimental lung injury. Pulmonary Klf2 was down-regulated by inflammation induced by influenza A/WSN/H1N1 virus (H1N1) infection, LPS administration, or LPS administration followed by high tidal volume ventilation in vivo (Fig. 1). It was also down-regulated by pathologic stretch and inflammatory stimuli (Fig. 2). Knockdown of endogenous KLF2 reduces Rac1 activation in human pulmonary microvascular cells, whereas adenovirus-mediated transduction with KLF2 promoted Rac1 activation (Fig. 3). Computational predictive pathway analysis suggested that KLF2 acts to regulate ARDS-associated GWAS genes, including ACE, NAD(P)H, NQO1, SERPINE1/PAI-1, TNF, and NF-kappaB. Expression studies in mice confirmed this regulatory role (Fig. 8). Overexpression of KLF2 in vivo in mice could also mitigate lung injury and expression of inflammatory genes (Fig. 7).
COVID-19 research v0.348 IRF2 Rebecca Foulger commented on gene: IRF2: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): IRF2 encodes interferon regulatory factor 2, a member of the family of transcription factors that play a role in regulating both the innate and adaptive immune response. IRF2 is an antiviral IFN-stimulated gene (ISG) which negatively regulates IFN signalling. (Lukele et al. 2019 -review). In both cell culture and the knock out Irf2-/- mouse model, Irf2 deficiency leads to an increase in susceptibility to viral infection (Schoggins et al. 2011; Karki et al. 2012; Matsuyama et al. 1993; Grieder et al. 1999). Irf2-/- mice also show increased susceptibility to neurotrophic viruses, including SINV and VSV, when compared to wild type mice. The compromised development and maturation of multiple immune cell types in the Irf2−/− mice which lead to reduced B cells and virus specific IgG levels in the brains of infected mice was linked to the pathogenic phenotype (Melody et al. 2016). These data suggest IRF2 may also play an important role in the development of the immune system.

PMID: 21478870 Schoggins et al. (2011) - The authors over expressed over 380 ISGs to test their ability to inhibit the replication of viruses including hepatitis C virus (HCV), yellow fever virus (YFV), West Nile virus (WNV), chikungunya virus (CHIKV), Venezuelan equine encephalitis virus (VEEV), and human immunodeficiency virus (HIV-1). Each gene was expressed in a lentiviral construct transfected into various cell lines. Cells were challenged with GFP expressing virus and replication was quantified by flow cytometry. IRF2 was shown to be a anti-HCV ISGs.

PMID: 22615998 Karki et al. (2012) - Karki et al. used a library of lentiviruses individually expressing more than 350 ISGs, transduced in HuH-7 cells in the presence of absence of ZAP and identified IRF2 as an enhancer of viral inhibition upon infection with SINV. In confirmatory experiments, when both ZAP and IRF2 were knocked down, viral replication was significantly increased compared to ZAP or IRF2 silencing alone, which supports the results obtained in the ISG overexpression screen and suggests that endogenous ZAP and IRF2 might interact in a synergistic manner (Fig. 5).

PMID: 10208925 Grieder et al. (1999) - Irf2−/− mice show increased susceptibility to virulent Venezuelan equine encephalitis (VEE) virus infection even after vaccination with attenuated VEE, suggesting IRF2 is required to mount a protective immune response (Grieder and Vogel, 1999)

PMID: 22113474 Gao et al. (2012) - The authors found IRF2 variants to be risk alleles for atopic dermatitis and eczema herpeticum. Eight SNPs were found to be significantly associated with reduced IFN-γ production after stimulation with herpes simplex virus. In the cohort, none of the SNPs showed association with HSV positivity.

PMID: 27899441 Melody et al. (2016) - Fig 1. Lrf2 mice show lethality upon peritoneal infection with either SINV or VSV virus (Fig 1) Irf2−/− and WT mice were challenged i.p. with SVN, a neurovirulent but noninvasive strain, which normally replicates only in the periphery without lethality in mice. Approximately 70% of the Irf2−/− mice succumbed to infection with SVN, whereas all of the WT littermate control mice survived (Fig. 1 A), indicating that IRF2 deficiency confers lethal neuroinvasive properties on the normally noninvasive SVN strain. Infection with VSV led to survival of all the WT mice, whereas ∼60% of the Irf2−/− mice suffered from paralysis and succumbed to infection. Staining using Evans blue showed that the integrity of the blood brain barrier is maintained during the infection(fig 2). The survival of lrf-/- mice treated with IFNAR-1 blocking antibody at 2dpi was similar to treatment with a control antibody, suggesting that peripheral elevation of type I IFN signalling is not responsible for the susceptibility (fig 3). Development and maturation of multiple immune cell subsets are compromised in Irf2−/− mice at baseline and upon SVN infection. B cells and virus-specific IgG level are significantly reduced in Irf2 -/- mouse brains, periorbital injection of naïve Bcells from WT mice 1day before infection did not affect lethality in the lrf2-/1 mice.
COVID-19 research v0.348 IFNE Rebecca Foulger commented on gene: IFNE: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): IFNE encodes IFNε, a type I interferon which is constitutively expressed within the epithelial cells of the female reproductive tract (FRT) and plays a role in protection against viral and bacterial infections of the FRT (Marks et al. 2019 review). Ifnε-deficient mice have increased susceptibility to infection of the FRT by Herpes Simplex Virus (HSV)-2 as well as bacterial Chlamydia muridarum(Fung et al. 2013). Ifnε activity has also been shown to reduce the infectivity of HIV through the induction of HIV restriction factors which act to inhibit different stages of the virus replication cycle (Garcia-Minambres et al. 2017; Stifter et al. 2018).

PMID: 31734130: Marks et al (2019) Review - IFNE encodes IFNε, a type I interferon which is constitutively expressed within the epithelial cells of the female reproductive tract. Ifnε expression fluctuates during pregnancy and across stages of the reproductive cycle in humans and mice. Unlike other type I interferons IFNε is not regulated by PRR pathways.

PMID: 23449591; Fung et al. 2013 - Ifnε-deficient mice had increased susceptibility to infection of the FRT by common sexually transmitted infections (STIs) Herpes Simplex Virus (HSV)-2 (fig 3) as measured by clinical scores of disease day 6 post infection. The Ifnε-deficient mice also showed high viral titres in the spinal cord and brain stem 7 days post infection, consistent with increase replication of the virus and/or retrograde transport of the virus. A similar susceptibility to infection by the bacterial Chlamydia muridarum was also observed (Fig 4).

PMID: 28045025 Garcia-Minambres et al. (2017) - Ifnε activity was shown to impair HIV infection through induction of HIV restriction factors which act to inhibit different stages of the viral replication cycle.

PMID: 29187603 Stifter et al. (2018) - Using different cell lines and reporter assays to measure interferon type I stimulation, the authors showed that recombinant murine Ifnε inhibited HIV infection in the sup-T1 cell line and in primary peripheral blood lymphocytes and furthermore induced a number of HIV restriction factors.
COVID-19 research v0.348 FOLR1 Rebecca Foulger commented on gene: FOLR1: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): The FOLR1 gene encodes the folate receptor alpha (FR alpha), a glycosyl-phosphatidylinositol-linked (GPI-linked) protein that binds folic acid for transport into the cytoplasm. Chan et al. (2001) used genetic complementation to identify FR-alpha as a cofactor for cellular entry of pseudo Marburg (MBG) virus and EBO-Z pseudotype into otherwise non permissive cells. Further experiments showed FR alpha specifically binds glycoproteins of these viruses to mediate syncytia (Chan et al. 2001).

PMID 11461707; Chan et al. (2001) - A complementation screen identified FR alpha as a cofactor for cellular entry of pseudo Marburg (MBG) virus into otherwise non permissive Jurkat-EctR cells (fig 1). FACs analysis showed FR alpha was present on the cell surface of other cell lines permissive for MBG infectivity (Hela cells, Vero E6, human and dog osteosarcoma cells (fig 2). FR alpha specific antagonists inhibited MBG entry (Fig 4) phospholipase C (PLC) cleaves the FR alpha receptor, cells pretreated with PLC showed decreased infectivity. When 293T cells overexpressing MBF GP were co-cultured with cells overexpressing FR alpha syncytia formation was observed, indicating that this type of membrane fusion is also mediated by FRalpha (fig 5). A similar set of experiments showed that FR alpha is also a cofactor for cellular entry of EBO-Z pseudo viruses.

Yang et al. (2019) preprint: https://doi.org/10.1101/618306 - Poliovirus (PV), a prototype for human pathogenic positive-sense RNA enteroviruses, transport multiple virions en bloc via infectious extracellular vesicles secreted from host cells. Yang et al. show that in these microvesicles less than 10% of proteins are viral. 168 host cell proteins were identified in the MVs including involved in both caveolar-mediated and mediated endocytic virus entry pathways genes (ITGB1, B2M, FYN, CD55 {DAF}, HLA-A, FLNA, ACTB, RAC1, TFRC {CD71}, FOLR1).
COVID-19 research v0.348 DICER1 Rebecca Foulger changed review comment from: Evidence Summary from Illumina curation team: The DICER1 gene, located on chromosome 14, position q32.13, was discovered in 2001 by Bernstein and is a member of the RNase III family, (also known as dicer 1, ribonuclease III; dicer1, Dcr-1 homolog (Drosophila); multinodular goitre 1). DICER1 is involved in the generation of double-stranded microRNAs (miRNAs), short non-coding RNAs, the cleavage of dsRNA into siRNAs, along with the biogenesis of numerous other small RNAs. There is increasing evidence DICER1 is also involved in regulating many other essential cellular processes such as those related to chromatin remodeling, inflammation, apoptosis and cell survival (Kurzynska-Kokorniak et al. 2015; Song and Rossi, 2017). DICER1 encodes a ∼220-KDa protein (RNase III endoribonuclease) which is a crucial component of the RNA Induced Silencing Complex (RISC) loading complex (RLC), comprised of dicer, Argonaute-2 (AGO-2), and trans-activation-responsive RNA binding protein 2 (TARBP2). The encoded protein is required by the RNA interference (RNAi) and small temporal RNA (stRNA) pathways to produce the active small RNA component which has a role in modulating gene expression at the post-transcriptional level. Research has shown that expression levels of cellular transcript and protein dicer are strictly controlled, with aberrant regulation contributing to carcinogenesis, neurodegenerative, rheumatic and immune system disorders. Studies have concluded that the encoded dicer ribonuclease-dependent processing of dsRNA viral replication intermediates into successive siRNAs is a conserved mammalian immune response to infection by positive-strand RNA viruses (Svobodova et al. 2016 summary & fig1; Li et al. 2013; Ding et al. 2018). Moreover, miRNAs play an important role in host-virus interactions in mammals (See Maillard et al. 2019 REVIEW; Foulkes et al. 2014 REVIEW).

IMMUNE SYSTEM
The cre-lox method for dicer1 gene knockout has been employed for studies into the role of dicer1 in immune cell development and function. Studies of dicer1 fl/fl mice have indicated short survival times along with severely impaired GMP differentiation into monocytes, neutrophils, myeloid DCs & mature macrophages. (Devasthanam et al. 2014). Results conclude that dicer1 is important in immune response and also vital for cell survival and apoptosis pathways. Muljo et al. (2005) investigated a conditional allele of dicer-1 (dcr-1) within a mouse model and showed that specific dcr-1 deletion in the T-cell lineage, resulted in impaired development of T-cells & aberrant cell differentiation of T-helper cells & cytokine production. Dcr-1 deletion in the thymus resulted in severe block in development of CD8+ T cells and resulted in defective microRNA processing in CD4+ T-cells. The results demonstrate Dicer regulates diverse aspects of T-cell biology along with cytokine production during T-cell differentiation where dicer-deficient T-cells preferentially express interferon-ƴ.

VIRUSES
Research by Galiana-Arnoux et al. (2006), of DICER in drosophila (drosophila have two dicer genes) have identified that DICER genes (Dcr1, miRNA pathway and Dcr2, RNAi pathway) control production of siRNA and a loss-of-function mutation in Dcr2 resulted in increased susceptibility to three different families of RNA viruses. Qi et al. (2012) research into RNAi gene silencing mechanism show that the B2 protein in Wuhan nodavirus (WhNV) suppresses Dcr2 in drosophila by direct interaction with the PAZ and RNAse III domains therefore blocking processing of dsRNA and siRNA. Evidence of a dicer antiviral system was also reported by Machitani et al. (2016) for mammalian human adenoviruses where DICER1 gene knockdown increased the copy number of adenovirus-encoding small RNAs (VA-RNAs) leading to the promotion of adenovirus replication; conversely, dicer overexpression significantly inhibited viral replication.
Modai et al. (2019) conclude that HIV-1 infection inhibits DICER1 by altering miRNA expression. They conclude that upon HIV-1 infection, human miR-186, 210 and 222 directly regulate DICER1 gene expression causing down-regulation of the gene contributing to impaired cell-mediated immunity (fig6). Other methods of inhibition are from viral proteins, termed viral suppressors of RNA silencing, which interact and inhibit dicer ribonuclease activity in HIV-1 and hepatitis C infections. These viral proteins may mediate proteasomal degradation of endoribonuclease dicer through CRL4DCAF1 ubiquitin ligase complex (Klockow et al. 2013), interact directly via the core protein (Chen et al. 2008) or HIV-1 transactivation of transcription (Bennasser and Jeang, 2006). Through these methods they can block dicer interactions with TRBP2 or ADAR1, boost macrophage infection, and subsequently reduce the function of short hairpin RNAs (shRNAs) which thus inhibit RNA silencing. Ultimately these viruses, though various methods, supress the ability of dicer to process dsRNAs into siRNAs boosting viral infection and pathogenesis.
Downregulation of DICER1 gene expression has additionally been found in cord blood of infants with severe respiratory syncytial virus (RSV), prior to RSV exposure, indicating this reduced expression may predispose newborns to RSV disease. Inchley et al. (2011) theorize that this occurs via disruption of leukocyte gene regulation of miRNA and direct anti-viral RNAi mechanisms. (Inchley et al. 2011 see section on “Dicer Gene Expression”).
Otsuka et al. (2007) have shown using gene-trap methods to obtain viable dicer1 fl/fl mice where dicer1 deficiency caused impairment of miR24 and miR93 production resulting in susceptibility to vesticular stomatitis virus (VSV) and herpes simplex-1 virus, but not other viruses tested.

SARS CoV & SARS CoV-2
Recently, Pasquier and Robichon, 2020 (preprint) have investigated the Dicer host immunity system regarding SARs-CoV-2 within a computational approach, concluding SARS-CoV2 may manipulate this system of immunity against its host, requiring further research. Mu et al., 2020 suggest SARs-CoV2 suppresses RNAi thus preventing recognition by the encoded ribonuclease dicer protein
Viral suppressors of RNA silencing (VSRs) suppress RNAi at pre or post-dicer level to overcome host defense and establish infection. Cui et al. (2015) from Wuhan University laboratory of virology, identified a novel VSR from coronaviruses (CoVs) including Severe acute respiratory syndrome coronavirus (SARS-CoV) and showed that the coronavirus nucelocaspid protein (N-protein), conserved and expressed in all coronaviruses, suppressed RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. They went on to show using mouse hepatitis virus A-59 (MHV-A59) which is closely linked to SARS-CoV in the family coronaviridae, that the viral replication was increased when the N proteins (novel VSR) were expressed but that knockdown of DICER1 gene or Ago2 transcripts facilitated the viral replication specifically in mammalian cells. They demonstrate that the N-protein of CoVs could efficiently inhibit dicer-mediated dsRNA cleavage and post-Dicer activities by sequestering dsRNAs and siRNAs. Kannan et al. (2020) performed clustal W analysis of N-Protein for SARS-CoV and COVID-19 demonstrating 90% sequence identity from an NCBI amino acid blast of both nucleocapsid (N) protein sequences (figure2). They suggest that the N-protein of COVID-19 may also function as a VSR for RNAi to overcome host defense. Ding et al. (2017) show that both MHV and SARS-CoV N proteins can also disrupt protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein which binds to RIG-I and MDA5 to activate interferon (IFN) production to prevent antiviral host response.

Literature Review
PMID: 17181864: Bennasser and Jeang, 2006
• HIV-1 Tat Interaction With Dicer: Requirement for RNA
• Tat-Dicer interaction depends on RNA, requires the helicase domain of Dicer, and is independent of Tat's transactivation domain.

PMID: 18325616: Chen et al., 2008
• HCV Core Protein Interacts With Dicer to Antagonize RNA Silencing

PMID: 26085159: Cui et al., 2015
• The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells

PMID: 24303839: Devasthanam et al, 2014
• This study investigates the role of the dicer protein in immune cell development and function using dicer1 cre-lox knockout models to conditionally ablate dicer1 in different immune cell subsets.

PMID: 28591694: Ding et al., 2017
• The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/MDA5 activation

PMID: 30015086: Ding et al., 2018
• Antiviral RNA Interference in Mammals: Indicates infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi).

PMID: 25176334: Foulkes et al., 2012-REVIEW
• Review of DICER1: DICER1 Mutations, microRNAs and Mechanisms

PMID: 16554838: Galiana-Arnoux et al., 2006
• Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.
• https://pubmed.ncbi.nlm.nih.gov/16554838/ or https://www.nature.com/articles/ni1335

PMID: 21385408: Inchley et al., 2011
• Investigates ribonuclease Dicer and analyzed the gene expression of Dicer in newborns of which 37 infants had sufficient cord blood RNA with confirmed RSV disease <1yr. Demonstrates significant reduced Dicer expression in cord blood prior to severe disease in infants <1yr later. Conclude downregulation may predispose infants to RSV disease.

PMID: 32141569: Kannan et al., 2020
• COVID-19 (Novel Coronavirus 2019) - Recent Trends
• Perform W cluster analysis of COVID-19 and SARS-CoV nucleocapsid (N) protein sequences of the viruses showing 90% amino acid sequence similarity. Suggest the N-protein may be a VSR in RNAi by targeting DICER.

PMID: 23849790: Klockow et al., 2013
• The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection

PMID: 25883138: Kurzynska-Kokorniak et al., 2015
• Investigating the complexity of the mechanisms regulating Dicer gene expression and enzyme activities

PMID: 24115437: Li et al, 2013
• Investigates RNA interference pathways in antiviral immunity in mammals overviewing dicer processing of dsRNA viral replication intermediates into siRNAs.

PMID: 27273616: Machitani et al., 2016
• Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA

PMID: 30872283: Maillard et al., 2019- REVIEW
• Reviewing DICER1 within the anti-viral RNAi pathway in mammals

PMID: 30682089: Modai et al, 2019
• HIV-1 infection increases miRNAs which inhibit Dicer

PMID: 32291557: Mu et al, 2020
• SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells

PMID: 16009718: Muljo et al., 2005
• Indicates absence of dicer results in abberant T-cell differentiation.

PMID: 17613256: Otsuka, et al 2007
• Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression

No PMID: Preprint : Pasquier and Rubichon, 2020
• SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system

PMID: 22438534: Qi et al., 2012
• Targeting of Dicer-2 and RNA by a Viral RNA Silencing Suppressor in Drosophila Cells

PMID: 28473628: Song and Rossi, 2017
• Molecular Mechanisms of Dicer: Endonuclease and Enzymatic Activity; to: Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): The DICER1 gene, located on chromosome 14, position q32.13, was discovered in 2001 by Bernstein and is a member of the RNase III family, (also known as dicer 1, ribonuclease III; dicer1, Dcr-1 homolog (Drosophila); multinodular goitre 1). DICER1 is involved in the generation of double-stranded microRNAs (miRNAs), short non-coding RNAs, the cleavage of dsRNA into siRNAs, along with the biogenesis of numerous other small RNAs. There is increasing evidence DICER1 is also involved in regulating many other essential cellular processes such as those related to chromatin remodeling, inflammation, apoptosis and cell survival (Kurzynska-Kokorniak et al. 2015; Song and Rossi, 2017). DICER1 encodes a ∼220-KDa protein (RNase III endoribonuclease) which is a crucial component of the RNA Induced Silencing Complex (RISC) loading complex (RLC), comprised of dicer, Argonaute-2 (AGO-2), and trans-activation-responsive RNA binding protein 2 (TARBP2). The encoded protein is required by the RNA interference (RNAi) and small temporal RNA (stRNA) pathways to produce the active small RNA component which has a role in modulating gene expression at the post-transcriptional level. Research has shown that expression levels of cellular transcript and protein dicer are strictly controlled, with aberrant regulation contributing to carcinogenesis, neurodegenerative, rheumatic and immune system disorders. Studies have concluded that the encoded dicer ribonuclease-dependent processing of dsRNA viral replication intermediates into successive siRNAs is a conserved mammalian immune response to infection by positive-strand RNA viruses (Svobodova et al. 2016 summary & fig1; Li et al. 2013; Ding et al. 2018). Moreover, miRNAs play an important role in host-virus interactions in mammals (See Maillard et al. 2019 REVIEW; Foulkes et al. 2014 REVIEW).

IMMUNE SYSTEM
The cre-lox method for dicer1 gene knockout has been employed for studies into the role of dicer1 in immune cell development and function. Studies of dicer1 fl/fl mice have indicated short survival times along with severely impaired GMP differentiation into monocytes, neutrophils, myeloid DCs & mature macrophages. (Devasthanam et al. 2014). Results conclude that dicer1 is important in immune response and also vital for cell survival and apoptosis pathways. Muljo et al. (2005) investigated a conditional allele of dicer-1 (dcr-1) within a mouse model and showed that specific dcr-1 deletion in the T-cell lineage, resulted in impaired development of T-cells & aberrant cell differentiation of T-helper cells & cytokine production. Dcr-1 deletion in the thymus resulted in severe block in development of CD8+ T cells and resulted in defective microRNA processing in CD4+ T-cells. The results demonstrate Dicer regulates diverse aspects of T-cell biology along with cytokine production during T-cell differentiation where dicer-deficient T-cells preferentially express interferon-ƴ.

VIRUSES
Research by Galiana-Arnoux et al. (2006), of DICER in drosophila (drosophila have two dicer genes) have identified that DICER genes (Dcr1, miRNA pathway and Dcr2, RNAi pathway) control production of siRNA and a loss-of-function mutation in Dcr2 resulted in increased susceptibility to three different families of RNA viruses. Qi et al. (2012) research into RNAi gene silencing mechanism show that the B2 protein in Wuhan nodavirus (WhNV) suppresses Dcr2 in drosophila by direct interaction with the PAZ and RNAse III domains therefore blocking processing of dsRNA and siRNA. Evidence of a dicer antiviral system was also reported by Machitani et al. (2016) for mammalian human adenoviruses where DICER1 gene knockdown increased the copy number of adenovirus-encoding small RNAs (VA-RNAs) leading to the promotion of adenovirus replication; conversely, dicer overexpression significantly inhibited viral replication.
Modai et al. (2019) conclude that HIV-1 infection inhibits DICER1 by altering miRNA expression. They conclude that upon HIV-1 infection, human miR-186, 210 and 222 directly regulate DICER1 gene expression causing down-regulation of the gene contributing to impaired cell-mediated immunity (fig6). Other methods of inhibition are from viral proteins, termed viral suppressors of RNA silencing, which interact and inhibit dicer ribonuclease activity in HIV-1 and hepatitis C infections. These viral proteins may mediate proteasomal degradation of endoribonuclease dicer through CRL4DCAF1 ubiquitin ligase complex (Klockow et al. 2013), interact directly via the core protein (Chen et al. 2008) or HIV-1 transactivation of transcription (Bennasser and Jeang, 2006). Through these methods they can block dicer interactions with TRBP2 or ADAR1, boost macrophage infection, and subsequently reduce the function of short hairpin RNAs (shRNAs) which thus inhibit RNA silencing. Ultimately these viruses, though various methods, supress the ability of dicer to process dsRNAs into siRNAs boosting viral infection and pathogenesis.
Downregulation of DICER1 gene expression has additionally been found in cord blood of infants with severe respiratory syncytial virus (RSV), prior to RSV exposure, indicating this reduced expression may predispose newborns to RSV disease. Inchley et al. (2011) theorize that this occurs via disruption of leukocyte gene regulation of miRNA and direct anti-viral RNAi mechanisms. (Inchley et al. 2011 see section on “Dicer Gene Expression”).
Otsuka et al. (2007) have shown using gene-trap methods to obtain viable dicer1 fl/fl mice where dicer1 deficiency caused impairment of miR24 and miR93 production resulting in susceptibility to vesticular stomatitis virus (VSV) and herpes simplex-1 virus, but not other viruses tested.

SARS CoV & SARS CoV-2
Recently, Pasquier and Robichon, 2020 (preprint) have investigated the Dicer host immunity system regarding SARs-CoV-2 within a computational approach, concluding SARS-CoV2 may manipulate this system of immunity against its host, requiring further research. Mu et al., 2020 suggest SARs-CoV2 suppresses RNAi thus preventing recognition by the encoded ribonuclease dicer protein
Viral suppressors of RNA silencing (VSRs) suppress RNAi at pre or post-dicer level to overcome host defense and establish infection. Cui et al. (2015) from Wuhan University laboratory of virology, identified a novel VSR from coronaviruses (CoVs) including Severe acute respiratory syndrome coronavirus (SARS-CoV) and showed that the coronavirus nucelocaspid protein (N-protein), conserved and expressed in all coronaviruses, suppressed RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. They went on to show using mouse hepatitis virus A-59 (MHV-A59) which is closely linked to SARS-CoV in the family coronaviridae, that the viral replication was increased when the N proteins (novel VSR) were expressed but that knockdown of DICER1 gene or Ago2 transcripts facilitated the viral replication specifically in mammalian cells. They demonstrate that the N-protein of CoVs could efficiently inhibit dicer-mediated dsRNA cleavage and post-Dicer activities by sequestering dsRNAs and siRNAs. Kannan et al. (2020) performed clustal W analysis of N-Protein for SARS-CoV and COVID-19 demonstrating 90% sequence identity from an NCBI amino acid blast of both nucleocapsid (N) protein sequences (figure2). They suggest that the N-protein of COVID-19 may also function as a VSR for RNAi to overcome host defense. Ding et al. (2017) show that both MHV and SARS-CoV N proteins can also disrupt protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein which binds to RIG-I and MDA5 to activate interferon (IFN) production to prevent antiviral host response.

Literature Review
PMID: 17181864: Bennasser and Jeang, 2006
• HIV-1 Tat Interaction With Dicer: Requirement for RNA
• Tat-Dicer interaction depends on RNA, requires the helicase domain of Dicer, and is independent of Tat's transactivation domain.

PMID: 18325616: Chen et al., 2008
• HCV Core Protein Interacts With Dicer to Antagonize RNA Silencing

PMID: 26085159: Cui et al., 2015
• The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells

PMID: 24303839: Devasthanam et al, 2014
• This study investigates the role of the dicer protein in immune cell development and function using dicer1 cre-lox knockout models to conditionally ablate dicer1 in different immune cell subsets.

PMID: 28591694: Ding et al., 2017
• The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/MDA5 activation

PMID: 30015086: Ding et al., 2018
• Antiviral RNA Interference in Mammals: Indicates infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi).

PMID: 25176334: Foulkes et al., 2012-REVIEW
• Review of DICER1: DICER1 Mutations, microRNAs and Mechanisms

PMID: 16554838: Galiana-Arnoux et al., 2006
• Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.
• https://pubmed.ncbi.nlm.nih.gov/16554838/ or https://www.nature.com/articles/ni1335

PMID: 21385408: Inchley et al., 2011
• Investigates ribonuclease Dicer and analyzed the gene expression of Dicer in newborns of which 37 infants had sufficient cord blood RNA with confirmed RSV disease <1yr. Demonstrates significant reduced Dicer expression in cord blood prior to severe disease in infants <1yr later. Conclude downregulation may predispose infants to RSV disease.

PMID: 32141569: Kannan et al., 2020
• COVID-19 (Novel Coronavirus 2019) - Recent Trends
• Perform W cluster analysis of COVID-19 and SARS-CoV nucleocapsid (N) protein sequences of the viruses showing 90% amino acid sequence similarity. Suggest the N-protein may be a VSR in RNAi by targeting DICER.

PMID: 23849790: Klockow et al., 2013
• The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection

PMID: 25883138: Kurzynska-Kokorniak et al., 2015
• Investigating the complexity of the mechanisms regulating Dicer gene expression and enzyme activities

PMID: 24115437: Li et al, 2013
• Investigates RNA interference pathways in antiviral immunity in mammals overviewing dicer processing of dsRNA viral replication intermediates into siRNAs.

PMID: 27273616: Machitani et al., 2016
• Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA

PMID: 30872283: Maillard et al., 2019- REVIEW
• Reviewing DICER1 within the anti-viral RNAi pathway in mammals

PMID: 30682089: Modai et al, 2019
• HIV-1 infection increases miRNAs which inhibit Dicer

PMID: 32291557: Mu et al, 2020
• SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells

PMID: 16009718: Muljo et al., 2005
• Indicates absence of dicer results in abberant T-cell differentiation.

PMID: 17613256: Otsuka, et al 2007
• Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression

No PMID: Preprint : Pasquier and Rubichon, 2020
• SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system

PMID: 22438534: Qi et al., 2012
• Targeting of Dicer-2 and RNA by a Viral RNA Silencing Suppressor in Drosophila Cells

PMID: 28473628: Song and Rossi, 2017
• Molecular Mechanisms of Dicer: Endonuclease and Enzymatic Activity
COVID-19 research v0.348 DICER1 Rebecca Foulger commented on gene: DICER1: Evidence Summary from Illumina curation team: The DICER1 gene, located on chromosome 14, position q32.13, was discovered in 2001 by Bernstein and is a member of the RNase III family, (also known as dicer 1, ribonuclease III; dicer1, Dcr-1 homolog (Drosophila); multinodular goitre 1). DICER1 is involved in the generation of double-stranded microRNAs (miRNAs), short non-coding RNAs, the cleavage of dsRNA into siRNAs, along with the biogenesis of numerous other small RNAs. There is increasing evidence DICER1 is also involved in regulating many other essential cellular processes such as those related to chromatin remodeling, inflammation, apoptosis and cell survival (Kurzynska-Kokorniak et al. 2015; Song and Rossi, 2017). DICER1 encodes a ∼220-KDa protein (RNase III endoribonuclease) which is a crucial component of the RNA Induced Silencing Complex (RISC) loading complex (RLC), comprised of dicer, Argonaute-2 (AGO-2), and trans-activation-responsive RNA binding protein 2 (TARBP2). The encoded protein is required by the RNA interference (RNAi) and small temporal RNA (stRNA) pathways to produce the active small RNA component which has a role in modulating gene expression at the post-transcriptional level. Research has shown that expression levels of cellular transcript and protein dicer are strictly controlled, with aberrant regulation contributing to carcinogenesis, neurodegenerative, rheumatic and immune system disorders. Studies have concluded that the encoded dicer ribonuclease-dependent processing of dsRNA viral replication intermediates into successive siRNAs is a conserved mammalian immune response to infection by positive-strand RNA viruses (Svobodova et al. 2016 summary & fig1; Li et al. 2013; Ding et al. 2018). Moreover, miRNAs play an important role in host-virus interactions in mammals (See Maillard et al. 2019 REVIEW; Foulkes et al. 2014 REVIEW).

IMMUNE SYSTEM
The cre-lox method for dicer1 gene knockout has been employed for studies into the role of dicer1 in immune cell development and function. Studies of dicer1 fl/fl mice have indicated short survival times along with severely impaired GMP differentiation into monocytes, neutrophils, myeloid DCs & mature macrophages. (Devasthanam et al. 2014). Results conclude that dicer1 is important in immune response and also vital for cell survival and apoptosis pathways. Muljo et al. (2005) investigated a conditional allele of dicer-1 (dcr-1) within a mouse model and showed that specific dcr-1 deletion in the T-cell lineage, resulted in impaired development of T-cells & aberrant cell differentiation of T-helper cells & cytokine production. Dcr-1 deletion in the thymus resulted in severe block in development of CD8+ T cells and resulted in defective microRNA processing in CD4+ T-cells. The results demonstrate Dicer regulates diverse aspects of T-cell biology along with cytokine production during T-cell differentiation where dicer-deficient T-cells preferentially express interferon-ƴ.

VIRUSES
Research by Galiana-Arnoux et al. (2006), of DICER in drosophila (drosophila have two dicer genes) have identified that DICER genes (Dcr1, miRNA pathway and Dcr2, RNAi pathway) control production of siRNA and a loss-of-function mutation in Dcr2 resulted in increased susceptibility to three different families of RNA viruses. Qi et al. (2012) research into RNAi gene silencing mechanism show that the B2 protein in Wuhan nodavirus (WhNV) suppresses Dcr2 in drosophila by direct interaction with the PAZ and RNAse III domains therefore blocking processing of dsRNA and siRNA. Evidence of a dicer antiviral system was also reported by Machitani et al. (2016) for mammalian human adenoviruses where DICER1 gene knockdown increased the copy number of adenovirus-encoding small RNAs (VA-RNAs) leading to the promotion of adenovirus replication; conversely, dicer overexpression significantly inhibited viral replication.
Modai et al. (2019) conclude that HIV-1 infection inhibits DICER1 by altering miRNA expression. They conclude that upon HIV-1 infection, human miR-186, 210 and 222 directly regulate DICER1 gene expression causing down-regulation of the gene contributing to impaired cell-mediated immunity (fig6). Other methods of inhibition are from viral proteins, termed viral suppressors of RNA silencing, which interact and inhibit dicer ribonuclease activity in HIV-1 and hepatitis C infections. These viral proteins may mediate proteasomal degradation of endoribonuclease dicer through CRL4DCAF1 ubiquitin ligase complex (Klockow et al. 2013), interact directly via the core protein (Chen et al. 2008) or HIV-1 transactivation of transcription (Bennasser and Jeang, 2006). Through these methods they can block dicer interactions with TRBP2 or ADAR1, boost macrophage infection, and subsequently reduce the function of short hairpin RNAs (shRNAs) which thus inhibit RNA silencing. Ultimately these viruses, though various methods, supress the ability of dicer to process dsRNAs into siRNAs boosting viral infection and pathogenesis.
Downregulation of DICER1 gene expression has additionally been found in cord blood of infants with severe respiratory syncytial virus (RSV), prior to RSV exposure, indicating this reduced expression may predispose newborns to RSV disease. Inchley et al. (2011) theorize that this occurs via disruption of leukocyte gene regulation of miRNA and direct anti-viral RNAi mechanisms. (Inchley et al. 2011 see section on “Dicer Gene Expression”).
Otsuka et al. (2007) have shown using gene-trap methods to obtain viable dicer1 fl/fl mice where dicer1 deficiency caused impairment of miR24 and miR93 production resulting in susceptibility to vesticular stomatitis virus (VSV) and herpes simplex-1 virus, but not other viruses tested.

SARS CoV & SARS CoV-2
Recently, Pasquier and Robichon, 2020 (preprint) have investigated the Dicer host immunity system regarding SARs-CoV-2 within a computational approach, concluding SARS-CoV2 may manipulate this system of immunity against its host, requiring further research. Mu et al., 2020 suggest SARs-CoV2 suppresses RNAi thus preventing recognition by the encoded ribonuclease dicer protein
Viral suppressors of RNA silencing (VSRs) suppress RNAi at pre or post-dicer level to overcome host defense and establish infection. Cui et al. (2015) from Wuhan University laboratory of virology, identified a novel VSR from coronaviruses (CoVs) including Severe acute respiratory syndrome coronavirus (SARS-CoV) and showed that the coronavirus nucelocaspid protein (N-protein), conserved and expressed in all coronaviruses, suppressed RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. They went on to show using mouse hepatitis virus A-59 (MHV-A59) which is closely linked to SARS-CoV in the family coronaviridae, that the viral replication was increased when the N proteins (novel VSR) were expressed but that knockdown of DICER1 gene or Ago2 transcripts facilitated the viral replication specifically in mammalian cells. They demonstrate that the N-protein of CoVs could efficiently inhibit dicer-mediated dsRNA cleavage and post-Dicer activities by sequestering dsRNAs and siRNAs. Kannan et al. (2020) performed clustal W analysis of N-Protein for SARS-CoV and COVID-19 demonstrating 90% sequence identity from an NCBI amino acid blast of both nucleocapsid (N) protein sequences (figure2). They suggest that the N-protein of COVID-19 may also function as a VSR for RNAi to overcome host defense. Ding et al. (2017) show that both MHV and SARS-CoV N proteins can also disrupt protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein which binds to RIG-I and MDA5 to activate interferon (IFN) production to prevent antiviral host response.

Literature Review
PMID: 17181864: Bennasser and Jeang, 2006
• HIV-1 Tat Interaction With Dicer: Requirement for RNA
• Tat-Dicer interaction depends on RNA, requires the helicase domain of Dicer, and is independent of Tat's transactivation domain.

PMID: 18325616: Chen et al., 2008
• HCV Core Protein Interacts With Dicer to Antagonize RNA Silencing

PMID: 26085159: Cui et al., 2015
• The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells

PMID: 24303839: Devasthanam et al, 2014
• This study investigates the role of the dicer protein in immune cell development and function using dicer1 cre-lox knockout models to conditionally ablate dicer1 in different immune cell subsets.

PMID: 28591694: Ding et al., 2017
• The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/MDA5 activation

PMID: 30015086: Ding et al., 2018
• Antiviral RNA Interference in Mammals: Indicates infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi).

PMID: 25176334: Foulkes et al., 2012-REVIEW
• Review of DICER1: DICER1 Mutations, microRNAs and Mechanisms

PMID: 16554838: Galiana-Arnoux et al., 2006
• Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.
• https://pubmed.ncbi.nlm.nih.gov/16554838/ or https://www.nature.com/articles/ni1335

PMID: 21385408: Inchley et al., 2011
• Investigates ribonuclease Dicer and analyzed the gene expression of Dicer in newborns of which 37 infants had sufficient cord blood RNA with confirmed RSV disease <1yr. Demonstrates significant reduced Dicer expression in cord blood prior to severe disease in infants <1yr later. Conclude downregulation may predispose infants to RSV disease.

PMID: 32141569: Kannan et al., 2020
• COVID-19 (Novel Coronavirus 2019) - Recent Trends
• Perform W cluster analysis of COVID-19 and SARS-CoV nucleocapsid (N) protein sequences of the viruses showing 90% amino acid sequence similarity. Suggest the N-protein may be a VSR in RNAi by targeting DICER.

PMID: 23849790: Klockow et al., 2013
• The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection

PMID: 25883138: Kurzynska-Kokorniak et al., 2015
• Investigating the complexity of the mechanisms regulating Dicer gene expression and enzyme activities

PMID: 24115437: Li et al, 2013
• Investigates RNA interference pathways in antiviral immunity in mammals overviewing dicer processing of dsRNA viral replication intermediates into siRNAs.

PMID: 27273616: Machitani et al., 2016
• Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA

PMID: 30872283: Maillard et al., 2019- REVIEW
• Reviewing DICER1 within the anti-viral RNAi pathway in mammals

PMID: 30682089: Modai et al, 2019
• HIV-1 infection increases miRNAs which inhibit Dicer

PMID: 32291557: Mu et al, 2020
• SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells

PMID: 16009718: Muljo et al., 2005
• Indicates absence of dicer results in abberant T-cell differentiation.

PMID: 17613256: Otsuka, et al 2007
• Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression

No PMID: Preprint : Pasquier and Rubichon, 2020
• SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system

PMID: 22438534: Qi et al., 2012
• Targeting of Dicer-2 and RNA by a Viral RNA Silencing Suppressor in Drosophila Cells

PMID: 28473628: Song and Rossi, 2017
• Molecular Mechanisms of Dicer: Endonuclease and Enzymatic Activity
COVID-19 research v0.348 CD28 Rebecca Foulger commented on gene: CD28: Evidence Summary from Illumina curation team: CD28 is a transmembrane receptor expressed on the surface of T cells and is required for the immune cell activation and proliferation of naïve and memory T cells. CD28 knockout mice have an increased susceptibility to ECTV, a host specific virus which causes mousepox. Upon infection, CD28 deficient mice showed a 40% mortality within 14 days while wild-type control mice did not show any symptoms of disease (Fang et al. 2008). In cell culture experiments, CD28 protein surface levels were found to be downregulated by HIV-1 accessory proteins Nef and Vpu (Pawlak et al. 2018). In severe cases of COVID-19 infection, immuno-dysregulation may lead to a decrease of CD28+ cytotoxic suppressor T cells (Tufan et al. 2020, review)

PMID: 29329537; Pawlak et al.(2018) - CD28 is a transmembrane receptor expressed on the surface of T cells. It is essential for immune cell activation and proliferation of naïve and memory T cell. Cell culture experiments using CD4+ Sup-T1 cells or primary CD4+ T cells and infected with VSV-G pseudotyped NL4.3 viruses showed that the HIV-1 accessory proteins Nef and Vpu modify the immune response and increase viral persistence by decreasing the cell surface levels of CD28 (fig.1).

PMID: 32299202; Tufan et al. (2020) Review. SARS-CoV-2 infection can lead to immune dysregulation through affecting the subset of T cells. In severe cases of COVID-19 infection, it was observed that the percentage of naïve helper T cells amplifies while the percentage of memory helper T cells and CD28+ cytotoxic suppressor T cells decreases.

PMID: 17114476; Fang et al. (2008) - CD28 KO mice in a mousepox-resistant B6 background infected with ECTV showed a 40% mortality 7–14 days PI (Fig. 1A) and all remaining CD28KO mice developed mousepox (Fig. 1, B and C). All control wild-type B6 mice survived the infection without any symptoms of disease. CD28 KO mice that survived past 14 days PI gradually recovered from the disease and survived indefinitely. A comparison of CD8+ T cell responses to ECTV and VACV suggests that the main reason for the susceptibility of CD28 KO mice to mousepox is a reduced response at the early stages of infection.
COVID-19 research v0.348 CCR2 Rebecca Foulger changed review comment from: Evidence Summary from Illumina curation team:
CCR2 is a chemokine receptor highly expressed on monocytes which is critical for bone marrow egress of classic monocytes and trafficking to sites of inflammation. Ccr2 deficiency in mice markedly increases mortality in West Nile virus encephalitis, with Ccr2-/- mice showing sustained monocytopenia, reduced accumulation of monocytes in the brain and an increase in cerebral viral load (Lim et al, 2011). CCR2 has been reported to mediate increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17 (Gurczynski et al, 2019). Nine SNPs in the CCR2 gene have been associated with susceptibility to and severity of several diseases including HIV and hepatitis C virus infection (Stone et al, 2017 Review; Ngoufack et al, 2019).
PMID: 21131425; Lim et al, 2011 - Ccr2-deficiency resulted in markedly increased mortality (~20% survival). This was associated with increased viral load in the CNS of Ccr2-deficient mice on day 12 post-infection. This appeared to be specific to the brain and not in the blood. Monocyte accumulation is strongly reduced in Ccr2-/- mice. Brain tissue from infected Ccr2−/− mice showed markedly fewer immunoreactive cells as evaluated by immunohistochemistry analysis (Fig4).

PMID: 30498200; Gurczynski et al, 2019 - H1N1 infected CCR2−/− mice had significantly higher survival as compared to H1N1 infected WT mice which is associated with significantly improved bacterial clearance at 24 and 48 hours (10 fold and 14 fold, respectively) post-bacterial challenge (with MRSA). In comparison to WT H1N1 infected mice, CCR2−/− mice recruited ~3-fold more IL-17 producing γδ-T cells and ~2.5-fold more Th17 cells (Figure 4B). Expression of CCL2 (MCP-1) in the lung is increased following H1N1 infection or H1N1 / MRSA dual infection as measured via qRT-PCR (Fig1).; to: Evidence Summary from Illumina curation team: CCR2 is a chemokine receptor highly expressed on monocytes which is critical for bone marrow egress of classic monocytes and trafficking to sites of inflammation. Ccr2 deficiency in mice markedly increases mortality in West Nile virus encephalitis, with Ccr2-/- mice showing sustained monocytopenia, reduced accumulation of monocytes in the brain and an increase in cerebral viral load (Lim et al, 2011). CCR2 has been reported to mediate increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17 (Gurczynski et al, 2019). Nine SNPs in the CCR2 gene have been associated with susceptibility to and severity of several diseases including HIV and hepatitis C virus infection (Stone et al, 2017 Review; Ngoufack et al, 2019).

PMID: 21131425; Lim et al, 2011 - Ccr2-deficiency resulted in markedly increased mortality (~20% survival). This was associated with increased viral load in the CNS of Ccr2-deficient mice on day 12 post-infection. This appeared to be specific to the brain and not in the blood. Monocyte accumulation is strongly reduced in Ccr2-/- mice. Brain tissue from infected Ccr2−/− mice showed markedly fewer immunoreactive cells as evaluated by immunohistochemistry analysis (Fig4).

PMID: 30498200; Gurczynski et al, 2019 - H1N1 infected CCR2−/− mice had significantly higher survival as compared to H1N1 infected WT mice which is associated with significantly improved bacterial clearance at 24 and 48 hours (10 fold and 14 fold, respectively) post-bacterial challenge (with MRSA). In comparison to WT H1N1 infected mice, CCR2−/− mice recruited ~3-fold more IL-17 producing γδ-T cells and ~2.5-fold more Th17 cells (Figure 4B). Expression of CCL2 (MCP-1) in the lung is increased following H1N1 infection or H1N1 / MRSA dual infection as measured via qRT-PCR (Fig1).
COVID-19 research v0.348 CCR2 Rebecca Foulger changed review comment from: Evidence Summary from Illumina curation team: CCR2 is a chemokine receptor highly expressed on monocytes which is critical for bone marrow egress of classic monocytes and trafficking to sites of inflammation. Ccr2 deficiency in mice markedly increases mortality in West Nile virus encephalitis, with Ccr2-/- mice showing sustained monocytopenia, reduced accumulation of monocytes in the brain and an increase in cerebral viral load (Lim et al, 2011). CCR2 has been reported to mediate increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17 (Gurczynski et al, 2019). Nine SNPs in the CCR2 gene have been associated with susceptibility to and severity of several diseases including HIV and hepatitis C virus infection (Stone et al, 2017 Review; Ngoufack et al, 2019).
PMID: 21131425; Lim et al, 2011 - Ccr2-deficiency resulted in markedly increased mortality (~20% survival). This was associated with increased viral load in the CNS of Ccr2-deficient mice on day 12 post-infection. This appeared to be specific to the brain and not in the blood. Monocyte accumulation is strongly reduced in Ccr2-/- mice. Brain tissue from infected Ccr2−/− mice showed markedly fewer immunoreactive cells as evaluated by immunohistochemistry analysis (Fig4).

PMID: 30498200; Gurczynski et al, 2019 - H1N1 infected CCR2−/− mice had significantly higher survival as compared to H1N1 infected WT mice which is associated with significantly improved bacterial clearance at 24 and 48 hours (10 fold and 14 fold, respectively) post-bacterial challenge (with MRSA). In comparison to WT H1N1 infected mice, CCR2−/− mice recruited ~3-fold more IL-17 producing γδ-T cells and ~2.5-fold more Th17 cells (Figure 4B). Expression of CCL2 (MCP-1) in the lung is increased following H1N1 infection or H1N1 / MRSA dual infection as measured via qRT-PCR (Fig1).; to: Evidence Summary from Illumina curation team:
CCR2 is a chemokine receptor highly expressed on monocytes which is critical for bone marrow egress of classic monocytes and trafficking to sites of inflammation. Ccr2 deficiency in mice markedly increases mortality in West Nile virus encephalitis, with Ccr2-/- mice showing sustained monocytopenia, reduced accumulation of monocytes in the brain and an increase in cerebral viral load (Lim et al, 2011). CCR2 has been reported to mediate increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17 (Gurczynski et al, 2019). Nine SNPs in the CCR2 gene have been associated with susceptibility to and severity of several diseases including HIV and hepatitis C virus infection (Stone et al, 2017 Review; Ngoufack et al, 2019).
PMID: 21131425; Lim et al, 2011 - Ccr2-deficiency resulted in markedly increased mortality (~20% survival). This was associated with increased viral load in the CNS of Ccr2-deficient mice on day 12 post-infection. This appeared to be specific to the brain and not in the blood. Monocyte accumulation is strongly reduced in Ccr2-/- mice. Brain tissue from infected Ccr2−/− mice showed markedly fewer immunoreactive cells as evaluated by immunohistochemistry analysis (Fig4).

PMID: 30498200; Gurczynski et al, 2019 - H1N1 infected CCR2−/− mice had significantly higher survival as compared to H1N1 infected WT mice which is associated with significantly improved bacterial clearance at 24 and 48 hours (10 fold and 14 fold, respectively) post-bacterial challenge (with MRSA). In comparison to WT H1N1 infected mice, CCR2−/− mice recruited ~3-fold more IL-17 producing γδ-T cells and ~2.5-fold more Th17 cells (Figure 4B). Expression of CCL2 (MCP-1) in the lung is increased following H1N1 infection or H1N1 / MRSA dual infection as measured via qRT-PCR (Fig1).
COVID-19 research v0.348 CCR2 Rebecca Foulger changed review comment from: Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.; to: Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
COVID-19 research v0.348 CCR2 Rebecca Foulger commented on gene: CCR2: Evidence Summary from Illumina curation team: CCR2 is a chemokine receptor highly expressed on monocytes which is critical for bone marrow egress of classic monocytes and trafficking to sites of inflammation. Ccr2 deficiency in mice markedly increases mortality in West Nile virus encephalitis, with Ccr2-/- mice showing sustained monocytopenia, reduced accumulation of monocytes in the brain and an increase in cerebral viral load (Lim et al, 2011). CCR2 has been reported to mediate increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17 (Gurczynski et al, 2019). Nine SNPs in the CCR2 gene have been associated with susceptibility to and severity of several diseases including HIV and hepatitis C virus infection (Stone et al, 2017 Review; Ngoufack et al, 2019).
PMID: 21131425; Lim et al, 2011 - Ccr2-deficiency resulted in markedly increased mortality (~20% survival). This was associated with increased viral load in the CNS of Ccr2-deficient mice on day 12 post-infection. This appeared to be specific to the brain and not in the blood. Monocyte accumulation is strongly reduced in Ccr2-/- mice. Brain tissue from infected Ccr2−/− mice showed markedly fewer immunoreactive cells as evaluated by immunohistochemistry analysis (Fig4).

PMID: 30498200; Gurczynski et al, 2019 - H1N1 infected CCR2−/− mice had significantly higher survival as compared to H1N1 infected WT mice which is associated with significantly improved bacterial clearance at 24 and 48 hours (10 fold and 14 fold, respectively) post-bacterial challenge (with MRSA). In comparison to WT H1N1 infected mice, CCR2−/− mice recruited ~3-fold more IL-17 producing γδ-T cells and ~2.5-fold more Th17 cells (Figure 4B). Expression of CCL2 (MCP-1) in the lung is increased following H1N1 infection or H1N1 / MRSA dual infection as measured via qRT-PCR (Fig1).
COVID-19 research v0.348 DSG2 Catherine Snow Publications for gene: DSG2 were set to
COVID-19 research v0.347 DSG2 Catherine Snow reviewed gene: DSG2: Rating: ; Mode of pathogenicity: None; Publications: 21151137, 30862836; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.347 ATF3 Rebecca Foulger changed review comment from: Evidence Summary from Illumina curation team: The Activating Transcription Factor 3 (ATF3) is a member of the ATF/cAMP Responsive Element-Binding (CREB) family of transcription factors which are known to be induced during inflammation and genotoxic stress. The modulation and elevation of ATF3 levels has also been observed in different host cells types upon infection with viruses, including the coronavirus, HCoV-229E and the Japanese encephalitis virus (JEV), a RNA neurotropic flavivirus (Poppe et al. 2016; Sood et al. (2017). In a mouse neuronal cell line infected with JEV, Atf3 was shown to bind to the promoter of viral response genes including Stat1, Irf9, Isg15, and to negatively regulate their expression (Sood et al. (2017). In addition, cellular autophagy was also inhibited by Atf3 negative regulation of the autophagy gene Atg5 in cells infected with the same virus (Sood et al. (2017). Labzin et al. (2015) also showed reduced viral replication in primary bone marrow–derived macrophages derived from Atf3 deficient mice, a phenotype which could be rescued by overexpression of Atf3.
PMID: 28355270: Poppe et al. (2016) -The A549 lung epithelial carcinoma cell model was used to assess host cell transcriptional changes upon infection of the corona virus HCoV-229E. At 16 h and 48 h post transfection, cell transcriptomes were analysed by microarray containing 60,000 probes covering annotated genes and non-coding RNAs. Thirty seven genes, including ATF3 were upregulated in response to the HCoV-229E infection when compared to mock transduced cells (Fig 1). Upregulation of ATF3 was confirmed by RT-PCR analysis of laser dissected cells (Fig 1E).
PMID 28821775; Sood et al. (2017) - ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. ATF3 was induced in mammalian cells following JEV infection, using qRTPCR analysis of transduced cell lines, including mouse Neuro2a, HEK293, HeLa and MEFs ATF3 levels were elevated compared to wildtype (Fig1). Fig2: ATF3 acts as a negative regulator of the antiviral response. Knockdown of ATF3 expression using Atf3 specific siRNA lead to a relative increased expression of viral response genes including Rig1, ifih1, ddx60, Gbp1, compared to controls. Fig4 CHIP analysis showed that ATF3 binds to the promoter of antiviral genes such as Stat1, Irf9, Isg15, Ifit1. Fig5 ATF3 negatively regulates cellular autophagy, in both Neur2a cells and MEFs infected with JEV and treated with Atf3 siRNA showed a relative increase in the expression of cellular autophagy related genes as determined by RTPCR. Fig 6. CHIP analysis showed that ATF3 binds the ATG5 promoter. Taken together this series of experiments demonstrate that, in cells deficient in interferon type I, the increased expression of ATF3 induced by infection of JEV leads to the negative regulation of antiviral genes such as Stat1, Irf9, Isg15 and genes related to cellular autophagy such as ATG5.
PMID 26416280; Labzin et al. (2015) - ATF3 limits cellular inflammatory response to microbial infection by regulating the expression of cytokines and chemokines. Primary bone marrow–derived macrophages from ATF3-/- mice infected with LCMV showed reduced viral replication compared to WT (Fig 7). The same cells overexpressing ATF3 constructs showed an increase in viral replication.; to: Evidence Summary from Illumina curation team: The Activating Transcription Factor 3 (ATF3) is a member of the ATF/cAMP Responsive Element-Binding (CREB) family of transcription factors which are known to be induced during inflammation and genotoxic stress. The modulation and elevation of ATF3 levels has also been observed in different host cells types upon infection with viruses, including the coronavirus, HCoV-229E and the Japanese encephalitis virus (JEV), a RNA neurotropic flavivirus (Poppe et al. 2016; Sood et al. (2017). In a mouse neuronal cell line infected with JEV, Atf3 was shown to bind to the promoter of viral response genes including Stat1, Irf9, Isg15, and to negatively regulate their expression (Sood et al. (2017). In addition, cellular autophagy was also inhibited by Atf3 negative regulation of the autophagy gene Atg5 in cells infected with the same virus (Sood et al. (2017). Labzin et al. (2015) also showed reduced viral replication in primary bone marrow–derived macrophages derived from Atf3 deficient mice, a phenotype which could be rescued by overexpression of Atf3.

PMID: 28355270: Poppe et al. (2016) -The A549 lung epithelial carcinoma cell model was used to assess host cell transcriptional changes upon infection of the corona virus HCoV-229E. At 16 h and 48 h post transfection, cell transcriptomes were analysed by microarray containing 60,000 probes covering annotated genes and non-coding RNAs. Thirty seven genes, including ATF3 were upregulated in response to the HCoV-229E infection when compared to mock transduced cells (Fig 1). Upregulation of ATF3 was confirmed by RT-PCR analysis of laser dissected cells (Fig 1E).

PMID 28821775; Sood et al. (2017) - ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. ATF3 was induced in mammalian cells following JEV infection, using qRTPCR analysis of transduced cell lines, including mouse Neuro2a, HEK293, HeLa and MEFs ATF3 levels were elevated compared to wildtype (Fig1). Fig2: ATF3 acts as a negative regulator of the antiviral response. Knockdown of ATF3 expression using Atf3 specific siRNA lead to a relative increased expression of viral response genes including Rig1, ifih1, ddx60, Gbp1, compared to controls. Fig4 CHIP analysis showed that ATF3 binds to the promoter of antiviral genes such as Stat1, Irf9, Isg15, Ifit1. Fig5 ATF3 negatively regulates cellular autophagy, in both Neur2a cells and MEFs infected with JEV and treated with Atf3 siRNA showed a relative increase in the expression of cellular autophagy related genes as determined by RTPCR. Fig 6. CHIP analysis showed that ATF3 binds the ATG5 promoter. Taken together this series of experiments demonstrate that, in cells deficient in interferon type I, the increased expression of ATF3 induced by infection of JEV leads to the negative regulation of antiviral genes such as Stat1, Irf9, Isg15 and genes related to cellular autophagy such as ATG5.

PMID 26416280; Labzin et al. (2015) - ATF3 limits cellular inflammatory response to microbial infection by regulating the expression of cytokines and chemokines. Primary bone marrow–derived macrophages from ATF3-/- mice infected with LCMV showed reduced viral replication compared to WT (Fig 7). The same cells overexpressing ATF3 constructs showed an increase in viral replication.
COVID-19 research v0.347 ATF3 Rebecca Foulger commented on gene: ATF3: Evidence Summary from Illumina curation team: The Activating Transcription Factor 3 (ATF3) is a member of the ATF/cAMP Responsive Element-Binding (CREB) family of transcription factors which are known to be induced during inflammation and genotoxic stress. The modulation and elevation of ATF3 levels has also been observed in different host cells types upon infection with viruses, including the coronavirus, HCoV-229E and the Japanese encephalitis virus (JEV), a RNA neurotropic flavivirus (Poppe et al. 2016; Sood et al. (2017). In a mouse neuronal cell line infected with JEV, Atf3 was shown to bind to the promoter of viral response genes including Stat1, Irf9, Isg15, and to negatively regulate their expression (Sood et al. (2017). In addition, cellular autophagy was also inhibited by Atf3 negative regulation of the autophagy gene Atg5 in cells infected with the same virus (Sood et al. (2017). Labzin et al. (2015) also showed reduced viral replication in primary bone marrow–derived macrophages derived from Atf3 deficient mice, a phenotype which could be rescued by overexpression of Atf3.
PMID: 28355270: Poppe et al. (2016) -The A549 lung epithelial carcinoma cell model was used to assess host cell transcriptional changes upon infection of the corona virus HCoV-229E. At 16 h and 48 h post transfection, cell transcriptomes were analysed by microarray containing 60,000 probes covering annotated genes and non-coding RNAs. Thirty seven genes, including ATF3 were upregulated in response to the HCoV-229E infection when compared to mock transduced cells (Fig 1). Upregulation of ATF3 was confirmed by RT-PCR analysis of laser dissected cells (Fig 1E).
PMID 28821775; Sood et al. (2017) - ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. ATF3 was induced in mammalian cells following JEV infection, using qRTPCR analysis of transduced cell lines, including mouse Neuro2a, HEK293, HeLa and MEFs ATF3 levels were elevated compared to wildtype (Fig1). Fig2: ATF3 acts as a negative regulator of the antiviral response. Knockdown of ATF3 expression using Atf3 specific siRNA lead to a relative increased expression of viral response genes including Rig1, ifih1, ddx60, Gbp1, compared to controls. Fig4 CHIP analysis showed that ATF3 binds to the promoter of antiviral genes such as Stat1, Irf9, Isg15, Ifit1. Fig5 ATF3 negatively regulates cellular autophagy, in both Neur2a cells and MEFs infected with JEV and treated with Atf3 siRNA showed a relative increase in the expression of cellular autophagy related genes as determined by RTPCR. Fig 6. CHIP analysis showed that ATF3 binds the ATG5 promoter. Taken together this series of experiments demonstrate that, in cells deficient in interferon type I, the increased expression of ATF3 induced by infection of JEV leads to the negative regulation of antiviral genes such as Stat1, Irf9, Isg15 and genes related to cellular autophagy such as ATG5.
PMID 26416280; Labzin et al. (2015) - ATF3 limits cellular inflammatory response to microbial infection by regulating the expression of cytokines and chemokines. Primary bone marrow–derived macrophages from ATF3-/- mice infected with LCMV showed reduced viral replication compared to WT (Fig 7). The same cells overexpressing ATF3 constructs showed an increase in viral replication.
COVID-19 research v0.347 IRF1 Julie Taylor commented on gene: IRF1: Evidence Summary from Illumina curation team: IRF1 encodes interferon regulatory factor 1, a member of the family of transcription factors that play a role in regulating both the innate and adaptive immune response. IRF1 is constitutively expressed at a low level but significantly elevated upon IFN-I stimulation, elevated IRF1 further amplifies the IFN response through a positive feedback loop (Lukele et al. 2019, Review). IRF-1 attenuates the replication of several viruses, including hepatitis C virus, West Nile virus (WNV), and EMCV, (Schoggins et al 2011) and IRF1 knock out mice are more susceptible to some viruses, such as EMCV and coxsackievirus B3, than wild type mice (Kimura et al. 1994). Using an IRF1 deficient BEAS2B bronchial epithelial cell line with increased susceptibility to VSV, and multiple strains of influenza viruses, Panda et al. 2019, showed that IRF1 is important for the early expression of types I and III IFNs and ISGs.
COVID-19 research v0.347 IDE Alison Coffey commented on gene: IDE: Evidence Summary from Illumina curation team: Insulin-degrading enzyme (IDE), also known as insulysin, is a member of the zinc metalloproteinase family that was initially implicated in insulin degradation. It is highly conserved among different species and has the ability to interact with a variety of functionally unrelated ligands that share little homology in their primary amino acid sequences. Several human viruses use enzymes as receptors. Li et al. (2006) (PMID 17055432) established IDE as a cellular receptor for both cell-free and cell-associated Varicella-zoster virus (VZV), the cause of chickenpox and shingles in humans. VZV is likely spread as cell-free virus to susceptible hosts but transmitted by cell-to-cell spread in the body and in vitro. Li et al. (2006) showed that IDE interacts with the VZV glycoprotein E (gE) (which is essential for virus infection) through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. Li et al. (2010) subsequently reported that a recombinant soluble IDE (rIDE) enhanced VZV infectivity at an early step of infection associated with an increase in virus internalization, and increased cell-to-cell spread. In 2017, Hahn et al. demonstrated that mature HIV-1 p6 protein (stability of which inversely affects the replication capacity of HIV-1) is a substrate for IDE. IDE is both sufficient and required for the degradation of p6, which is approximately 100-fold more efficiently degraded by IDE than its eponymous substrate insulin. An IDE specific inhibitor, 6bK, and exogenous insulin, were both shown to interfere with X4-tropic HIV-1 replication in activated PBMCs, most probably by competing with p6 for degradation by IDE. In addition, an IDE-insensitive p6 mutant of HIV-1 exhibits impaired replication capacity but is insensitive to treatment with insulin or 6bK. Conversely, neither virus release and maturation, nor the amounts of particle associated Vpr and p6 itself were altered in IDE knock out cells. The data support a model in which IDE is responsible for the rapid degradation of p6 entering the cell as part of the incoming virion, a process that appears to be crucial to achieve optimal X4-tropic virus replication.
COVID-19 research v0.347 DEFA1 Alison Coffey commented on gene: DEFA1: Evidence Summary from Illumina curation team: DEFA1, or HNP1, is a member of the defensin family of host defense peptides, a group of microbicidal and cytotoxic peptides made by neutrophils. Defensins are known to have a role in innate immunity as a core host-protective component against bacterial, viral and fungal infections (Xu and Wuyaun, 2020). Defensins have direct antiviral activity in cell culture, with varied mechanisms for individual viruses. Defensins also have a potent immunomodulatory activity that can alter innate and adaptive immune responses to viral infection and are able to target multiple steps of host-virus interactions to reduce infectivity of both enveloped and non-enveloped viruses. Targets include viral envelopes, glycoproteins, and capsids or host cells. DEFA1 is well-recognized for its direct anti-HIV activity, it also restrains HIV-1 uptake by inhibiting Env-mediated viral fusion and downregulating host cell surface expression of CD4 and coreceptor CXCR4. Post-entry inhibition of enveloped viruses such as HIV-1 and influenza by DEFA1 is mediated through interfering with cell signaling pathways such as PKC that are required for viral replication (Xu and Wuyaun, 2020). An unpublished study by Kit and Kit (2020), demonstrated in silico that the affinity of human alpha-defensins 1, 2, 3 and 5 to SARS-CoV-2 spike protein is higher than that of the SARS-CoV-2 spike protein towards ACE2. The authors suggest that these alpha-defensins may serve as primary factors in protecting lung tissue from COVID-19 viral infection.
COVID-19 research v0.347 CXADR Alison Coffey commented on gene: CXADR: Evidence Summary from Illumina curation team: The coxsackie and adenovirus receptor (CXADR or CAR), also known as CAR-like membrane protein (CLMP), was first identified as a high affinity receptor for adenovirus serotypes 2 and 5 and coxsackie viruses group B. CXADR is developmentally regulated and plays an important role in cardiac development. The protein is a transmembrane receptor and plays a key role in controlling adhesion between adjacent epithelial cells. It is also implicated in controlling both recruitment of immune cells and in tumorigenesis (Zapater et al. 2017). Vehik et al. (2018) concluded that a SNP within the CXADR region is associated with islet autoimmunity. In response to exogenous TNF?, CAR promotes transmigration of leukocytes both in vitro and in vivo. suggesting that CAR may be an important receptor in the control of inflammation. As neutrophils and T cells play a role in host immunity, these data suggest that CAR may be ideally positioned to modulate the immune response from the epithelial or endothelial cell compartments. (Morton et al 2016). CAR expression and infectivity with adenovirus (Ad) are increased in cystic fibrosis airway epithelial cells (Sharma et al. 2017).
COVID-19 research v0.347 BANF1 Alison Coffey commented on gene: BANF1: Evidence Summary from Illumina curation team: BANF1 is an abundant, highly conserved DNA binding protein involved in multiple pathways including mitosis, nuclear assembly, viral infection, chromatin and gene regulation and the DNA damage response. It is also essential for early development in metazoans and relevant to human physiology. Variants in the gene are associated with Nestor-Guillermo progeria syndrome (OMIM #614008). Different viral infections can lead to changes in the subcellular distribution of BANF1 infections with a B1 kinase-deficient vaccinia virus cause re-localization at sites of viral DNA accumulation in the cytoplasm, while no change in localization is found during infection with wild-type vaccinia. By contrast, in cells infected with Herpes Simplex Virus Type-1 (HSV-1) BAF localizes to the nucleus, where HSV-1 viral DNA replicates. BANF1 actively protects the genome by intercepting foreign DNA. This protective function is exploited by retroviruses for inhibiting self-destructing autointegration of retroviral DNA, thereby promoting integration of viral DNA into the host chromosome. However, with other viruses, including the poxvirus vaccinia and HSV-1, BANF1 has an antiviral activity by blocking viral DNA replication (PMID 2607214: Jamin et al. 2015).
COVID-19 research v0.347 VPS33A Alison Coffey commented on gene: VPS33A: Evidence Summary from Illumina curation team: VPS33A is a member of the Sec1/Munc18-related (SM) protein family and a core component of the class C core vacuole/endosome tethering (CORVET) and the homotypic fusion and protein sorting (HOPS) complexes (Vasilev et al. 2020). Both complexes are heterohexamers and share four subunits. VPS33A, VPS11, VPS16 and VPS18, involved in endolysosomal pathway. Deficiency of VPS33A was shown to affect susceptibility to certain viruses in cell culture, including Ebola and Marburg viruses (Carette et al. 2011), however no human studies confirming this association were identified.
COVID-19 research v0.347 TLR7 Alison Coffey commented on gene: TLR7: Evidence Summary from Illumina curation team: The TLR7 gene encodes for toll -like receptor 7 protein, an endosomal receptor that plays a key role in innate and adaptive immunity. Toll-like receptors are pattern recognition receptors, which control host immune response against pathogens through recognition of molecular signatures. TLR7 recognizes uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analog (reviewed by Freund et al. 2019). Tlr7 deficient mice show an increased susceptibility to West Nile Virus (Town et al. (2009) and recently, Mukherjee et al. (2019) identified TLR7 polymorphisms associated with susceptibility to viral infections in an East Asian population Mukherjee et al. (2019).
COVID-19 research v0.347 PDGFRA Alison Coffey commented on gene: PDGFRA: Evidence Summary from Illumina curation team: The PDGFRA gene encodes the platelet-derived growth factor receptor alpha protein, a tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC, binding of which leads to the activation of several signaling cascades, and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. PDGFRA has been demonstrated to be a critical receptor for human cytomegalovirus infection (PMID 18701889: Soroceanu et al. 2008). Di Pasquale et al. (2003) (PMID 14502277). also confirmed the role of PDGFRA and PDGFRB as receptors for adeno-associated virus type 5 (AAV-5). PMID 18701889: Soroceanu et al. 2008 - PDGFRA is specifically phosphorylated by both laboratory and clinical isolates of human cytomegalovirus (CMV) in various human cell types, resulting in activation of the phosphoinositide-3-kinase signaling pathway. Cells in which PDGFRA was genetically deleted or functionally blocked were nonpermissive to human CMV entry, viral gene expression, or infectious virus production. Reintroducing the human PDGFRA gene into knockout cells restored susceptibility to viral entry and essential viral gene expression. Blockade of receptor function with a humanized PDGFRA blocking antibody (IMC-3G3) or targeted inhibition of its kinase activity with a small molecule (Gleevec) completely inhibited human CMV viral internalization and gene expression in human epithelial, endothelial, and fibroblast cells. Viral entry in cells harboring endogenous PDGFRA was competitively inhibited by pretreatment with PDGF-AA. It was demonstrated that human CMV glycoprotein B directly interacts with PDGFRA, resulting in receptor tyrosine phosphorylation, and that glycoprotein B neutralizing antibodies inhibit human CMV-induced PDGFRA phosphorylation. The authors concluded that PDGFRA is a critical receptor required for human CMV infection, and thus a target for novel antiviral therapies.
COVID-19 research v0.347 NLRP6 Alison Coffey commented on gene: NLRP6: Evidence Summary from Illumina curation team: The NLRP6 gene encoding the NOD-like receptor family pyrin domain containing 6 is a member of the NLR family of proteins, that is highly expressed within the intestine and liver. The NLRP6 inflammasome plays an established role in the regulation of inflammation and host defence against microbes. Wang et al. (2015) demonstrated that NLRP6 also regulates intestinal antiviral innate immunity. NLRP6 knockout mice show increased susceptibility to infection from the single stranded RNA viruses; encephalomyocarditis virus and murine norovirus 1(MNV-1). Nlrp6 binds viral RNA via the RNA helicase Dhx15, the complex triggers the induction of type I/III interferons (IFNs) through the mitochondrial antiviral signaling protein (MAVS). Type I/III IFNs stimulate the expression of antiviral IFN-stimulated genes (ISGs), including Nlrp6 itself (Wang et al. 2015).
COVID-19 research v0.347 MX2 Alison Coffey commented on gene: MX2: Evidence Summary from Illumina curation team: MX2, also known as MXB is an interferon-induced dynamin like GTPAse with antiviral activity, which has been shown to affect the nuclear uptake and/or stability of the HIV-1 replication complex and the subsequent chromosomal integration of the proviral DNA (Goujon et al. 2013, Liu et al. 2015). However, resistance of several HIV strains to MX2-driven inhibition has been reported (Liu et al. 2015). Inhibition of other viruses, including HCV, Japanese encephalitis virus and Dengue virus of the Flaviviridae family as well as simian immunodeficiency virus and Herpesviruses has been reported (Goujon et al. 2013, Yi et al. 2019). In contrast to MX1, MX2 does not appear to be involved in regulation of several other viral infections, including influenza and Zika virus (Melen et al. 1996; Yi et al. 2019). Additionally, MX2 may be involved in nucleocytoplasmic transport and bears a nuclear localisation signal that appears essential for HCV inhibition (Melen et al. 1996; King et al. 2004, Yi et al. 2019). Of note, MX2 was described as an interferon response marker gene in preprint studies investigating expression profiles and related mechanisms in SARS-CoV-2 infection (Fagone et al. 2020, Li et al. 2020). Overall, inhibition of viral infection by MX2 appears to be virus type- and strain-specific, and some viruses potentially have developed mechanisms to resist MX2 function. No reports of any SNP associations of MX2 with viral susceptibility in humans have been identified.
COVID-19 research v0.347 KIAA0319L Alison Coffey commented on gene: KIAA0319L: Evidence Summary from Illumina curation team: KIAA0319L, also known as AAVR or AAVRL, encodes the KIAA0319 like protein, a type-I transmembrane protein which acts as an essential receptor for adeno-associated virus (AAV) and is involved in adeno-associated virus infection through endocytosis system (PMID 26814968: Pillay et al. 2016). Genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV infection. Adeno-associated virus vectors are widely used in virus-based gene therapy because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. PMID 26814968: Pillay et al. (2016) - used a haploid genetic screen to identify the type I transmembrane protein KIAA0319L as an essential receptor that mediates AAV entry and renamed this protein the AAV receptor (AAVR). The function of AAVR was confirmed by using CRISPRCas9 to knock out the receptor and by using anti-AAVR blocking antibodies; both treatments rendered cells highly resistant to AAV infection with several serotypes, including AAV2, which is the most commonly used serotype for gene therapy in clinical trials. Finally, Aavr knockout mice were more resistant to AAV-mediated gene therapy than mice that expressed AAVR. PMID 28679762: Pillay et al. (2017) - Further defines AAV-AAVR interactions, genetically and biochemically.
COVID-19 research v0.347 ITGB3 Alison Coffey commented on gene: ITGB3: Evidence Summary from Illumina curation team: ITGB3 encodes integrin beta-3 (CD61), a member of the integrin family of transmembrane proteins. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and migration, and organization of the cytoskeleton. Integrin b3 has been shown to act as a coreceptor for many viruses including Herpes virus 8/HHV-8, Coxsackievirus A9, Hantaan virus, Cytomegalovirus/HHV-5, and West Nile virus (Gavrilovskaya et al. 2008; Roivainen et al. 1994; Garrigues et al 2008; Schmidt et al. 2013; Wang et al. 2005). Viruses such as the arena virus LASV and Dengue virus may manipulate and increase the expression level of ITGB3 (Zapata et al, 2013; In vitro exposure of human PBMC to a pathogenic arenavirus (LASV) increases the expression of ITGB3 (Zapata et al, 2013; Noisakran et al, 2012). Valdebenito et al. 2019 recently reported a genetic single-nucleotide polymorphism associated with infection susceptibility to Andes virus in a Chilean population.
COVID-19 research v0.347 ITGAV Alison Coffey commented on gene: ITGAV: Evidence Summary from Illumina curation team: ITGAV or ALPHA-V is a component of the integrin family of transmembrane proteins. Integrins primary biological functions involve cell adhesion and migration, organization of the cytoskeleton, and other cellular functions. Alpha-V-containing integrins combine an alpha-V subunit with 1 of 5 beta subunits. Several families of viruses are known to use alpha-V-containing integrins for cell attachment and entry, including human adenovirus type 2/5, human CMV, HIV-1, EBV, rotavirus, Coxsackievirus, and Ebola virus (Hussein et al. 2015; LaFoya et al. 2018).
COVID-19 research v0.347 ILF3 Alison Coffey commented on gene: ILF3: Evidence Summary from Illumina curation team: The ILF3 gene encodes two alternatively spliced and ubiquitously expressed RNA binding protein isoforms, NF110 and NF90. NF110 and NF90 have been shown to interact with viral RNAs and proteins to inhibit the replication of a number of viruses, including PV-RIPO, a chimeric poliovirus and human rhinovirus; HIV-1, and vesicular stomatitis virus (VSV) (reviewed Castella et al. 2015). Conversely, NF110 and NF90 have also been associated with the enhancement of viral replication in the case of DNA hepatitis B virus (HBV), ssRNA viruses from the Flaviviridae family, hepatitis C virus and influenza B (FLUBV) (reviewed Castella et al. 2015; Patzina et al, 2017). Recently, Watson et al (2020) demonstrated a role for the ILF3 isoforms in enhancing the translation of IFNB1 and ISGs in response to a viral infection. Depletion of NF90/NF110 from HeLa cells using siRNA resulted in an impaired antiviral activity with a reduction in the expression of ISG proteins and conditioned medium generated in ILF3-depleted cells conferred less resistance to Echovirus 7 infection. The specific depletion of NF110 was shown to cause a decrease in the association of IFNB1 mRNA with the polysomal fractions in poly(I:C) stimulated conditions (Watson et al. 2020).
COVID-19 research v0.347 IL9 Alison Coffey commented on gene: IL9: Evidence Summary from Illumina curation team: IL9 encodes interleukin 9, which is a stimulatory cytokine that regulates inflammatory immunity (Goswami and Kaplan 2011). It has been demonstrated that high levels of IL-9 are present in nasopharyngeal aspirate of infants with disease of the respiratory tract caused by the Human respiratory syncytial virus (RSV) (Semple et al. 2007). Studies conducted on mice showed that that the severity of lung pathology correlates with IL-9 cytokine production and that Th9 cells, which produce IL-9, play an important role in the development of airway eosinophilia and bronchial hyperresponsiveness (Dodd et al. 2009; Saeki et al. 2016). IL9 polymorphisms have also been linked to sex-restricted differences in lung function, allergen sensitization, IgE levels, and the severity of respiratory syncytial virus infection (Schuurhof et al. 2010; Aschard et al. 2009).
COVID-19 research v0.347 IL3 Alison Coffey commented on gene: IL3: Evidence Summary from Illumina curation team: IL3 encodes a growth-promoting cytokine called interleukin 3, which is a member of the beta common cytokine family. IL-3 (Dougan et al. 2019). IL-3 acts to regulate inflammation induced by pathogens as well as in autoimmune disease and cancer. T cell production of IL-3 during inflammation plays a role in the activation of plasmacytoid dendritic cells during viral infection. IL-3 has also been suggested to play a host-protective role against herpes simplex virus (HSV) infection (Chan et al. 1990).
COVID-19 research v0.347 IFNA1 Alison Coffey commented on gene: IFNA1: Evidence Summary from Illumina curation team: IFNA1 encodes IFN alpha, and belongs to the family of type I IFNs which bind to and activate the IFNAR receptor complex. Type I Interferons (IFN-I) mediate numerous immune interactions during viral infections, they establish an antiviral state as well as invoke and regulate innate and adaptive immune cells that eliminate infection (Lukele et al. 2019, review; Wang et al.2019 review).
COVID-19 research v0.347 HAVCR1 Alison Coffey commented on gene: HAVCR1: Evidence Summary from Illumina curation team: HAVCR1 encodes the human hepatitis A virus (HAV) cellular receptor 1 (CD365, TIM1, KIM1) a phospholipid receptor which is expressed in mucosal epthelium from a range of tissues including trachea, conjunctiva and cornea (Kondratowicz et al. 2011). HAVCR1 acts as a cell receptor or entry factor for a number of enveloped viruses including Hepatitis A, Ebolavirus, Marberg virus and Dengue virus (Kondratowicz et al. 2011; Costfreda et al. 2018; Meertens et al. 2012).
COVID-19 research v0.347 GPR183 Alison Coffey commented on gene: GPR183: Evidence Summary from Illumina curation team: The GPR183 gene has been shown to be upregulated following infection with Epstein-Barr virus and aids in leukocyte migration into airways in response to allergens (Shen et al. 2017). GPR183 knockout mice exhibit enhanced pro-inflammatory cytokine release following an inflammation-inducing stimulus (Ruthiwska et al. 2018). In addition, recent work that has not yet been peer-reviewed found GPR183 expression on macrophages in severe Covid 19 patients (Liao et al.; https://doi.org/10.1101/2020.02.23.20026690). EBV seropositivity was also associated with fever and increased inflammation in Covid 19 patients in non-peer-reviewed work by Chen et al. (10.21203/rs.3.rs-21580/v1).
COVID-19 research v0.347 GPATCH3 Alison Coffey commented on gene: GPATCH3: Evidence Summary from Illumina curation team: Nie et al. (2017) showed that GPATCH3 is a negative regulator of the innate immune response to RNA viruses. Reduction of GPATCH3 levels using shRNA resulted in enhanced induction and transcription of SeV (ssRNA virus) downstream antiviral genes such as IFNB1, in multiple cell lines compared to controls. Similar effects were not observed in cells infected with DNA viruses, HCMV or HSV120. Coimmunoprecipitation and colocalisation experiments indicated that GPATCH3 negative regulation is mediated through a direct interaction of mitochondrial localised, MAVS (VISA). MAVS plays an established role in the innate antiviral immune responses against to RNA viruses.
COVID-19 research v0.347 GNAQ Alison Coffey commented on gene: GNAQ: Evidence Summary from Illumina curation team: The GNAQ gene encodes the Gq protein alpha subunit and belongs to the Gq/11 subfamily of heterotrimeric G proteins. GNAQ is ubiquitously expressed in mammalian cells and couples a wide variety of receptors to channel proteins, enzymes, and other effector molecules. Wang et al. (2019) found that Gnaq expression was downregulated during viral infection and that Gnaq siRNA transfection of host cells protected against infection from vesicular stomatitis virus (VSV) and HSV type 1 infection. Viral replication was also reduced in Gnaq deficient macrophages in cell culture and Gnaq-deficient mice were more resistant than wildtype mice to VSV infection. Further cell culture experiments showed that Gnaq modulated its antiviral response through the canonical PLC-b/Ca2+ signalling (Wang et al. 2019). PMID: 31324725 Wang et al. (2019) - Wang et al. demonstrated that GNAQ negatively regulates the antiviral innate immune responses in a calcineurin-dependent manner. Viral infection downregulates GNAQ expression in cell culture. mRNA expression levels were measured upon infection with VSV in mouse PEMs, BMMs,the fibroblast line L929 and the macrophage mouse line RAW264.7. Fig1. GNAQ negatively regulates host defence against viruses. Gnaq-specific siRNA knockdown reduced VSV infection in PEMS, overexpression of GNAQ in HEK293 cells increased VSV infection (Fig 2). PEMS and BMMs from myeloid cellspecific Gnaq-deficient mice showed reduced replication of VSV and HSV1 compared to WT. VSV replication and titers in the liver, spleen, and lung of Gnaq-deficient mice were all significantly lower than wt litter mates. Gnaq deficiency increases host resistance to viral infection (Fig 3). IFN-b (both mRNA and protein) was significantly enhanced in Gnaq-knockdown PEMs, Poly I;C (mimicking RNA viral infection), VSV infection and HSV-1 infection enhanced IgnBeta production in Gnaq-knockdown PEMs. In cell lines and in vivo, GNAQ negatively regulates IFN-beta production (Fig 4). GNAQ modulates antiviral innate immune responses through canonical PLC-b/Ca2+ signalling. Chemical inhibitors of the pathway reduced cell resistance to infection (Fig 5).
COVID-19 research v0.347 CLDN9 Alison Coffey commented on gene: CLDN9: Evidence Summary from Illumina curation team: CLDN9 gene encodes for the Claudin-9 protein. The claudin family constitutes a large group of four- transmembrane domain proteins that are essential for the formation of tight junctions responsible for the control of paracellular transport. Studies have demonstrated that CLDN9 and CLDN6 mediate the entry of the hepatitis C virus (HCV) into both hepatic and non-hepatic cell lines (Zheng et al. 2007) however, HCV infection is not dependent on the presence of CLDN9 (Fofana et al. 2013).
COVID-19 research v0.347 CLDN6 Alison Coffey commented on gene: CLDN6: Evidence Summary from Illumina curation team: CLDN6 gene encodes the Claudin-6 protein. The claudin family constitutes of a large group of four- transmembrane domain proteins that are essential for the formation of tight junctions responsible for the control of paracellular transport. Studies have demonstrated that CLDN6 and CLDN9 mediate the entry of the Hepatitis C virus (HCV) into both liver and non-liver cells (Zheng et al. 2007) however, HCV infection is not dependent on the presence of CLDN6 (Haid et al. 2014; Fofana et al. 2013).
COVID-19 research v0.347 CDKN1B Alison Coffey commented on gene: CDKN1B: Evidence Summary from Illumina curation team: CDKN1B, or p27(KIP1), is a cyclin-dependent kinase inhibitor that blocks the cell cycle in the G0/G1 phase upon differentiation signals or cellular insult (OMIM 600778). Karlas et al. (2010) identified p27/KIP as an inhibitor of influenza A viral replication in a genomewide RNA interference screen. The result was validated in the p27/KIP knockout mouse model, the viral load within these mice was significantly reduced two days after infection compared to control mice.
COVID-19 research v0.347 CD207 Alison Coffey commented on gene: CD207: Evidence Summary from Illumina curation team: The CD207 gene encodes the CD207 protein, also known as langerin, a cell surface C-type lectin expressed on Langerhans cells, the immature dendritic cells of the epidermis and mucosa. CD207 has a role as a pattern recognition receptor for a number of viruses including the Influenza A Virus (Ng et al. 2016), HIV-1 and HSV (reviewed by de Jong et al. 2010) and measles virus (van der Vlist et al. 2011).
COVID-19 research v0.347 CCR7 Alison Coffey commented on gene: CCR7: Evidence Summary from Illumina curation team: The CCR7 gene encodes the C-C chemokine receptor 7, a chemokine receptor which is a member of the G protein-coupled receptor superfamily. CCR7 plays an important role in the homing of central memory and nave T cells to peripheral lymphoid organs. The binding of CCR7 ligands CCL19 and CCL21 during viral infection promotes activation and differentiation of CCR7 expressing cells, as well as changes in their migration properties to modulate the immune response (reviewed Yan et al. 2019). Some viral proteins target CCR7 and reduce its expression during viral infection (reviewed Yan et al. 2019), for example, the HIV-1 accessory protein, Vpu, interacts directly with CCR7 to cause its retention within the trans Golgi network of primary CD4+ T cells (Ramirez et al. 2014).
COVID-19 research v0.347 ATG5 Alison Coffey commented on gene: ATG5: Evidence Summary from Illumina curation team: The ATG5 gene encodes a core autophagy protein which forms a complex with ATG12 and ATG16L that is important for autophagophore elongation. Autophagy plays a key antiviral role in various human infections by modulating different aspects of the immune response (Reviewed Tao et al. 2020; Ahmed et al.2018). ATG5 may play a role in cytokine regulation, in vitro, ATG5 depleted primary human blood macrophages produced lower levels of CXCL10 and IFNa when infected with influenza A virus (Law et al. 2007). ATG5 deficient mice also show reduced Ifn and Il22 secretion when infected with the single stranded RNA vesicular stomatitis virus (VSV) (Lee et al. 2007). Using a mouse model with a conditional depletion of ATG5 within dendritic cells, Lee et al. 2010 showed that ATG5 is required for antigen presentation by dendritic cells, as a result of reduced MHC-II antigen presentation, these mice, when intradermally injected with HSV-1, showed significantly lower IFNgamma production by CD4+ T cells. (Lee et al., 2010). The ATG5 complex is targeted by some viruses to enhance infection, for example, the foot and mouth disease virus (FMDV) targets the ATG5-ATG12 complex for degradation through its viral protein 3Cpro, similarly, depletion of ATG5 and ATG12 in vitro, by siRNA increased susceptibility to FMDV infection by reducing activation of the NF-?B and IRF3 pathways (Fan et al 2017).
COVID-19 research v0.347 ATG16L1 Alison Coffey commented on gene: ATG16L1: Evidence Summary from Illumina curation team: The ATG16L gene encodes a core autophagy protein which forms a complex with ATG5 and ATG12 that is important for autophagophore elongation (Lavoie et al. 2019). Autophagy plays a key antiviral role in various human infections by modulating different aspects of the immune response (Reviewed Tao et al. 2020; Ahmed et al. 2018). The ATG16L complex is also targeted by some viruses to enhance infection. The Zika virus protease, targets ATG16L, dramatically depleting its levels during Zika virus infection (Hill et al. 2018). Conversely, Hepatitis B virus (HBV), an enveloped pararetrovirus, stimulates autophagy to favor its production. In vitro, RNA interference-mediated silencing of Atg16L1 interfered with viral core/nucleocapsid (NC) formation and stability, strongly diminishing virus replication (Fletcher et al. 2018).
COVID-19 research v0.347 AIM2 Alison Coffey commented on gene: AIM2: Evidence summary from Illumina curation team: AIM2 performs an established role within the innate immune system as a pattern recognition receptor which senses microbial dsDNA. In vitro experiments have shown that AIM2 recognises cytosolic dsDNA from a number of viruses and consequently drives pyroptosis through formation of an inflammasome complex (Sharma et al. 2019). Aim2-deficient mice show an attenuated immune response upon infection with mCNV when compared to wildtype mice (Rathinam et al. 2010). PMID: 31372985 Sharma et al. 2019 (Review) AIM2 encodes a pattern recognition receptor which senses microbial dsDNA. In vitro experiments show AIM2 recognises cytosolic dsDNA from a number of viruses and consequently drives pyroptosis through formation of an inflammasome complex. AIM2 expression is upregulated in response to infection by RNA viruses and contributes to secretion of IL-1beta, the mechanism for the recognition of RNA viruses is unclear. Table 1 summarises the list of in vitro AIM2 virus studies. PMID: 20351692: Rathinam et al. 2010 In vivo, Aim2-deficient mice, Aim2- infected with mCMV have reduced IL-18 concentrations in the serum compared to wildtype mice, and severely attenuated IFN-? production by NK cells, events, which are critical for the early control of viral replication (Figure 7b, d, e) The spleen of infected Aim2-/- mice demonstrated elevated viral titre compared to the wildtype (Fig 7h, i). PMID: 26590313 Schattgen et al. 2018 Aim2 knockout mice, infected with influenza A virus (RNA virus) showed an exaggerated response to immune response. Authors suggest that host DNA released from damaged cells during IAV infection and sensed by AIM2 leads to limitation of immune mediated damage to infected tissues.
COVID-19 research v0.346 CXCR3 Catherine Snow Publications for gene: CXCR3 were set to 27412416; 19039768; 30109979; 26318079; 30467622
COVID-19 research v0.345 CXCR3 Catherine Snow Publications for gene: CXCR3 were set to
COVID-19 research v0.344 CXCR3 Catherine Snow reviewed gene: CXCR3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27412416, 19039768, 30109979, 26318079, 30467622; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.344 ATG16L1 Rebecca Foulger Publications for gene: ATG16L1 were set to
COVID-19 research v0.343 ATG16L1 Rebecca Foulger Classified gene: ATG16L1 as Amber List (moderate evidence)
COVID-19 research v0.343 ATG16L1 Rebecca Foulger Gene: atg16l1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.342 ATG16L1 Rebecca Foulger Classified gene: ATG16L1 as Red List (low evidence)
COVID-19 research v0.342 ATG16L1 Rebecca Foulger Added comment: Comment on list classification: Gene was originally added to panel as Red following initial triage by Illumina curation team (Alison Coffey and Julie Taylor). Updated rating to Amber to match revised Illumina review after literature curation.
COVID-19 research v0.342 ATG16L1 Rebecca Foulger Gene: atg16l1 has been classified as Red List (Low Evidence).
COVID-19 research v0.341 IRF1 Julie Taylor reviewed gene: IRF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 31155227, 31156620, 24719409, 21478870, 80092222; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IDE Alison Coffey reviewed gene: IDE: Rating: AMBER; Mode of pathogenicity: ; Publications: 17055432, 20593027, 28388673; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 HDAC6 Alison Coffey reviewed gene: HDAC6: Rating: GREEN; Mode of pathogenicity: ; Publications: 27959772, 31736889, 26746851, 25482409; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 DEFA1 Alison Coffey reviewed gene: DEFA1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32457744; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 DAG1 Alison Coffey reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16254364, 19324387, 17360738, 21185048:15857984; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CXADR Alison Coffey reviewed gene: CXADR: Rating: AMBER; Mode of pathogenicity: ; Publications: 28545889, 31792456, 27527752, 27193388; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 BECN1 Alison Coffey reviewed gene: BECN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32265919, 19635843, 18248095, 18005679; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 BANF1 Alison Coffey reviewed gene: BANF1: Rating: RED; Mode of pathogenicity: ; Publications: 2607214; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CXCL8 Alison Coffey reviewed gene: CXCL8: Rating: GREEN; Mode of pathogenicity: ; Publications: 3244677, 32161940, 15585888; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 VPS33A Alison Coffey reviewed gene: VPS33A: Rating: RED; Mode of pathogenicity: ; Publications: 21866103, 31936524; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 VPS11 Alison Coffey reviewed gene: VPS11: Rating: RED; Mode of pathogenicity: ; Publications: 21866103, 25375324, 26953343, 26958914; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 TLR7 Alison Coffey reviewed gene: TLR7: Rating: GREEN; Mode of pathogenicity: ; Publications: 19200759, 31481269, 29964062, 30699960; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 RNASEL Alison Coffey reviewed gene: RNASEL: Rating: GREEN; Mode of pathogenicity: ; Publications: 27595182, 16235172, 20479874, 9351818, 31156620, 22356654; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 PVR Alison Coffey reviewed gene: PVR: Rating: AMBER; Mode of pathogenicity: ; Publications: 28870470, 25113908, 19815499, 12943679, 17621371, 28800489, 2597248; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 PTX3 Alison Coffey reviewed gene: PTX3: Rating: AMBER; Mode of pathogenicity: ; Publications: 31031772, 18292565, 25695775, 18292565, 19968561; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 PDGFRA Alison Coffey reviewed gene: PDGFRA: Rating: AMBER; Mode of pathogenicity: ; Publications: 18701889, 14502277; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 NPC1 Alison Coffey reviewed gene: NPC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 21866103, 2186610, 26771495, 27238017; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 NLRP6 Alison Coffey reviewed gene: NLRP6: Rating: AMBER; Mode of pathogenicity: ; Publications: 26494172, 32386845 ; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 NECTIN1 Alison Coffey reviewed gene: NECTIN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 1175687, 12072525, 19805039; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 MX2 Alison Coffey reviewed gene: MX2: Rating: AMBER; Mode of pathogenicity: ; Publications: 24048477, 25571928, 30333168, 8798556, 15184662, 32345362 ; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 MIR155 Alison Coffey reviewed gene: MIR155: Rating: AMBER; Mode of pathogenicity: ; Publications: 32233818, 217121651, 1746328969, 20852130, 28139244, 23686237, 26072128, 32308197, 23601686, 23275599, 24516198; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 KLF2 Alison Coffey reviewed gene: KLF2: Rating: GREEN; Mode of pathogenicity: ; Publications: 17141159, 19592277, 22988032, 29125549, 27855271; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 KIAA0319L Alison Coffey reviewed gene: KIAA0319L: Rating: GREEN; Mode of pathogenicity: ; Publications: 26814968, 28679762; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ITGB3 Alison Coffey reviewed gene: ITGB3: Rating: GREEN; Mode of pathogenicity: ; Publications: 9618541, 7519807, 18045938, 23658209, 15834425, 22987294, 24069471, 30791508; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ITGAV Alison Coffey reviewed gene: ITGAV: Rating: GREEN; Mode of pathogenicity: ; Publications: 29393909, 26321473; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IRF2 Alison Coffey reviewed gene: IRF2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31155227, 21478870, 22615998, 8402903, 10208925, 22113474, 27899441; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ILF3 Alison Coffey reviewed gene: ILF3: Rating: AMBER; Mode of pathogenicity: ; Publications: 25327818, 31701124, 28869005; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IL9 Alison Coffey reviewed gene: IL9: Rating: AMBER; Mode of pathogenicity: ; Publications: 21368237, 17940602, 19915054, 27297515, 20503287, 19536153; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IL3 Alison Coffey reviewed gene: IL3: Rating: AMBER; Mode of pathogenicity: ; Publications: 2176641, 30995500; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IFNE Alison Coffey reviewed gene: IFNE: Rating: GREEN; Mode of pathogenicity: ; Publications: 31734130, 23449591, 28045025, 29187603; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 IFNA1 Alison Coffey reviewed gene: IFNA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 31155227, 31771760; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 HAVCR1 Alison Coffey reviewed gene: HAVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23084921, 29321304, 29437974, 21536871, 9658108; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 GPR183 Alison Coffey reviewed gene: GPR183: Rating: AMBER; Mode of pathogenicity: ; Publications: 29374507, 28125291, preprint: https://doi.org/10.1101/2020.02.23.20026690, preprint: 10.21203/rs.3.rs-21580/v1; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 GPATCH3 Alison Coffey reviewed gene: GPATCH3: Rating: AMBER; Mode of pathogenicity: ; Publications: 28414768; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 GNAQ Alison Coffey reviewed gene: GNAQ: Rating: AMBER; Mode of pathogenicity: ; Publications: 31324725; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 FOLR1 Alison Coffey reviewed gene: FOLR1: Rating: AMBER; Mode of pathogenicity: ; Publications: 11461707, preprint: https://doi.org/10.1101/618306; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 DICER1 Alison Coffey reviewed gene: DICER1: Rating: GREEN; Mode of pathogenicity: ; Publications: 17181864, 18325616, 26085159, 24303839, 28591694, 30015086, 25176334, 16554838, 21385408, 32141569, 23849790, 25883138, 24115437, 27273616, 30872283, 30682089, 32291557, 16009718, 17613256, 22438534, 28473628; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CLDN9 Alison Coffey reviewed gene: CLDN9: Rating: RED; Mode of pathogenicity: ; Publications: 17804490, 23864633; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CLDN6 Alison Coffey reviewed gene: CLDN6: Rating: RED; Mode of pathogenicity: ; Publications: 17804490, 23775920, 23864633; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CDKN1B Alison Coffey reviewed gene: CDKN1B: Rating: RED; Mode of pathogenicity: ; Publications: 20081832; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CD28 Alison Coffey reviewed gene: CD28: Rating: AMBER; Mode of pathogenicity: ; Publications: 29329537, 32299202; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CD207 Alison Coffey reviewed gene: CD207: Rating: AMBER; Mode of pathogenicity: ; Publications: 21030306, 21739428, 26468543; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CCR7 Alison Coffey reviewed gene: CCR7: Rating: AMBER; Mode of pathogenicity: ; Publications: 31632965, 24910430; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 CCR2 Alison Coffey reviewed gene: CCR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 21131425, 30498200, 28178200, 31777682; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ATG5 Alison Coffey reviewed gene: ATG5: Rating: AMBER; Mode of pathogenicity: ; Publications: 30510929, 32265919, 28102839, 20473322, 20171125, 17272685; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ATG16L1 Alison Coffey reviewed gene: ATG16L1: Rating: AMBER; Mode of pathogenicity: ; Publications: 30666959, 29367244, 32265919, 30510929; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 ATF3 Alison Coffey reviewed gene: ATF3: Rating: AMBER; Mode of pathogenicity: ; Publications: 28355270, 28821775, 26416280; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.341 AIM2 Alison Coffey reviewed gene: AIM2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31372985, 20351692, 26590313; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.340 FEZ1 Ivone Leong Publications for gene: FEZ1 were set to
COVID-19 research v0.339 DEFA1 Rebecca Foulger commented on gene: DEFA1
COVID-19 research v0.339 CXCL8 Rebecca Foulger commented on gene: CXCL8
COVID-19 research v0.339 MX2 Rebecca Foulger commented on gene: MX2
COVID-19 research v0.339 HAVCR1 Rebecca Foulger commented on gene: HAVCR1
COVID-19 research v0.339 DEFA1 Rebecca Foulger gene: DEFA1 was added
gene: DEFA1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: DEFA1 was set to Unknown
Publications for gene: DEFA1 were set to 32457744
COVID-19 research v0.339 CXCL8 Rebecca Foulger gene: CXCL8 was added
gene: CXCL8 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: CXCL8 was set to Unknown
Publications for gene: CXCL8 were set to 15585888; 32161940; 3244677
COVID-19 research v0.339 MX2 Rebecca Foulger gene: MX2 was added
gene: MX2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: MX2 was set to Unknown
Publications for gene: MX2 were set to 15184662; 24048477; 25571928; 8798556; 32345362; 30333168
COVID-19 research v0.339 HAVCR1 Rebecca Foulger gene: HAVCR1 was added
gene: HAVCR1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: HAVCR1 was set to Unknown
Publications for gene: HAVCR1 were set to 29321304; 21536871; 23084921; 29437974; 9658108
COVID-19 research v0.338 CD244 Ivone Leong reviewed gene: CD244: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.338 CD200 Sarah Leigh gene: CD200 was added
gene: CD200 was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: CD200 was set to Unknown
COVID-19 research v0.338 VPS4A Sarah Leigh gene: VPS4A was added
gene: VPS4A was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: VPS4A was set to Unknown
COVID-19 research v0.338 TPH1 Sarah Leigh gene: TPH1 was added
gene: TPH1 was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: TPH1 was set to Unknown
COVID-19 research v0.338 TNFSF4 Sarah Leigh gene: TNFSF4 was added
gene: TNFSF4 was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: TNFSF4 was set to Unknown
Phenotypes for gene: TNFSF4 were set to {Myocardial infarction, susceptibility to} 608446
COVID-19 research v0.338 TLR5 Sarah Leigh gene: TLR5 was added
gene: TLR5 was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: TLR5 was set to Unknown
Phenotypes for gene: TLR5 were set to {Legionnaire disease, susceptibility to} 608556
COVID-19 research v0.338 TLR4 Sarah Leigh gene: TLR4 was added
gene: TLR4 was added to COVID-19 research. Sources: OMIM
Mode of inheritance for gene: TLR4 was set to Unknown
COVID-19 research v0.337 CD244 Ivone Leong Publications for gene: CD244 were set to
COVID-19 research v0.336 CASP1 Ivone Leong reviewed gene: CASP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.336 IRF1 Rebecca Foulger commented on gene: IRF1
COVID-19 research v0.336 IDE Rebecca Foulger commented on gene: IDE
COVID-19 research v0.336 HDAC6 Rebecca Foulger commented on gene: HDAC6
COVID-19 research v0.336 FEZ1 Rebecca Foulger commented on gene: FEZ1
COVID-19 research v0.336 DSG2 Rebecca Foulger commented on gene: DSG2
COVID-19 research v0.336 DAG1 Rebecca Foulger commented on gene: DAG1
COVID-19 research v0.336 CXADR Rebecca Foulger commented on gene: CXADR
COVID-19 research v0.336 BECN1 Rebecca Foulger commented on gene: BECN1
COVID-19 research v0.336 BANF1 Rebecca Foulger commented on gene: BANF1
COVID-19 research v0.336 ABCC1 Rebecca Foulger commented on gene: ABCC1
COVID-19 research v0.336 ABCB1 Rebecca Foulger commented on gene: ABCB1
COVID-19 research v0.336 FCMR Rebecca Foulger commented on gene: FCMR
COVID-19 research v0.336 VPS33A Rebecca Foulger commented on gene: VPS33A
COVID-19 research v0.336 VPS11 Rebecca Foulger commented on gene: VPS11
COVID-19 research v0.336 TNFSF10 Rebecca Foulger commented on gene: TNFSF10
COVID-19 research v0.336 TLR7 Rebecca Foulger commented on gene: TLR7
COVID-19 research v0.336 RNASEL Rebecca Foulger commented on gene: RNASEL
COVID-19 research v0.336 PVR Rebecca Foulger commented on gene: PVR
COVID-19 research v0.336 PTX3 Rebecca Foulger commented on gene: PTX3
COVID-19 research v0.336 PDGFRA Rebecca Foulger commented on gene: PDGFRA
COVID-19 research v0.336 NPC1 Rebecca Foulger commented on gene: NPC1
COVID-19 research v0.336 NLRP6 Rebecca Foulger commented on gene: NLRP6
COVID-19 research v0.336 NECTIN1 Rebecca Foulger commented on gene: NECTIN1
COVID-19 research v0.336 MIR155 Rebecca Foulger commented on gene: MIR155
COVID-19 research v0.336 KLF2 Rebecca Foulger commented on gene: KLF2
COVID-19 research v0.336 KIAA0319L Rebecca Foulger commented on gene: KIAA0319L
COVID-19 research v0.336 ITGB3 Rebecca Foulger commented on gene: ITGB3
COVID-19 research v0.336 ITGAV Rebecca Foulger commented on gene: ITGAV
COVID-19 research v0.336 IRF2 Rebecca Foulger commented on gene: IRF2
COVID-19 research v0.336 ILF3 Rebecca Foulger commented on gene: ILF3
COVID-19 research v0.336 IL9 Rebecca Foulger commented on gene: IL9
COVID-19 research v0.336 IL3 Rebecca Foulger commented on gene: IL3
COVID-19 research v0.336 IFNE Rebecca Foulger commented on gene: IFNE
COVID-19 research v0.336 IFNA1 Rebecca Foulger commented on gene: IFNA1
COVID-19 research v0.336 GPR183 Rebecca Foulger commented on gene: GPR183
COVID-19 research v0.336 GPATCH3 Rebecca Foulger commented on gene: GPATCH3
COVID-19 research v0.336 GNAQ Rebecca Foulger commented on gene: GNAQ
COVID-19 research v0.336 FOLR1 Rebecca Foulger commented on gene: FOLR1
COVID-19 research v0.336 EIF3M Rebecca Foulger commented on gene: EIF3M
COVID-19 research v0.336 EGFR Rebecca Foulger commented on gene: EGFR
COVID-19 research v0.336 DICER1 Rebecca Foulger commented on gene: DICER1
COVID-19 research v0.336 CXCR3 Rebecca Foulger commented on gene: CXCR3
COVID-19 research v0.336 CLDN9 Rebecca Foulger commented on gene: CLDN9
COVID-19 research v0.336 CLDN6 Rebecca Foulger commented on gene: CLDN6
COVID-19 research v0.336 CDKN1B Rebecca Foulger commented on gene: CDKN1B
COVID-19 research v0.336 CD28 Rebecca Foulger commented on gene: CD28
COVID-19 research v0.336 CD244 Rebecca Foulger commented on gene: CD244
COVID-19 research v0.336 CD207 Rebecca Foulger commented on gene: CD207
COVID-19 research v0.336 CCR7 Rebecca Foulger commented on gene: CCR7
COVID-19 research v0.336 CCR2 Rebecca Foulger commented on gene: CCR2
COVID-19 research v0.336 CASP1 Rebecca Foulger commented on gene: CASP1
COVID-19 research v0.336 ATG5 Rebecca Foulger commented on gene: ATG5
COVID-19 research v0.336 ATG16L1 Rebecca Foulger commented on gene: ATG16L1
COVID-19 research v0.336 ATF3 Rebecca Foulger commented on gene: ATF3
COVID-19 research v0.336 AIM2 Rebecca Foulger commented on gene: AIM2
COVID-19 research v0.335 CASP1 Ivone Leong Publications for gene: CASP1 were set to
COVID-19 research v0.334 ABCC1 Ivone Leong reviewed gene: ABCC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.334 ABCB1 Ivone Leong edited their review of gene: ABCB1: Added comment: Searching through PubMed, most of the papers related to ABCB1 are to do with drug efficacy and ABCB1's affect on HIV-1 treatments. Therefore, this gene should remain rated Red.; Changed rating: RED
COVID-19 research v0.334 ABCB1 Ivone Leong Added comment: Comment on publications: PMID: 18547906 showed that ABCB1 SNP (C3435T) is associated with virological efficacy in treatments for HIV infected pateints.

PMID: 26922556 showed that SNPS in ABCB1 may influence HCV infectivity.
COVID-19 research v0.334 ABCB1 Ivone Leong Publications for gene: ABCB1 were set to
COVID-19 research v0.333 IRF1 Rebecca Foulger gene: IRF1 was added
gene: IRF1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: IRF1 was set to Unknown
COVID-19 research v0.333 IDE Rebecca Foulger gene: IDE was added
gene: IDE was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: IDE was set to Unknown
COVID-19 research v0.333 HDAC6 Rebecca Foulger gene: HDAC6 was added
gene: HDAC6 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: HDAC6 was set to Unknown
COVID-19 research v0.333 FEZ1 Rebecca Foulger gene: FEZ1 was added
gene: FEZ1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: FEZ1 was set to Unknown
COVID-19 research v0.333 DSG2 Rebecca Foulger gene: DSG2 was added
gene: DSG2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: DSG2 was set to Unknown
COVID-19 research v0.333 DAG1 Rebecca Foulger gene: DAG1 was added
gene: DAG1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: DAG1 was set to Unknown
COVID-19 research v0.333 CXADR Rebecca Foulger gene: CXADR was added
gene: CXADR was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: CXADR was set to Unknown
COVID-19 research v0.333 BECN1 Rebecca Foulger gene: BECN1 was added
gene: BECN1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: BECN1 was set to Unknown
COVID-19 research v0.333 BANF1 Rebecca Foulger gene: BANF1 was added
gene: BANF1 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: BANF1 was set to Unknown
COVID-19 research v0.333 ABCC1 Rebecca Foulger gene: ABCC1 was added
gene: ABCC1 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: ABCC1 was set to Unknown
COVID-19 research v0.333 ABCB1 Rebecca Foulger gene: ABCB1 was added
gene: ABCB1 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: ABCB1 was set to Unknown
COVID-19 research v0.333 FCMR Rebecca Foulger gene: FCMR was added
gene: FCMR was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: FCMR was set to Unknown
COVID-19 research v0.333 VPS33A Rebecca Foulger gene: VPS33A was added
gene: VPS33A was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: VPS33A was set to Unknown
COVID-19 research v0.333 VPS11 Rebecca Foulger gene: VPS11 was added
gene: VPS11 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: VPS11 was set to Unknown
COVID-19 research v0.333 TNFSF10 Rebecca Foulger gene: TNFSF10 was added
gene: TNFSF10 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: TNFSF10 was set to Unknown
COVID-19 research v0.333 TLR7 Rebecca Foulger gene: TLR7 was added
gene: TLR7 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: TLR7 was set to Unknown
COVID-19 research v0.333 RNASEL Rebecca Foulger gene: RNASEL was added
gene: RNASEL was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: RNASEL was set to Unknown
COVID-19 research v0.333 PVR Rebecca Foulger gene: PVR was added
gene: PVR was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: PVR was set to Unknown
COVID-19 research v0.333 PTX3 Rebecca Foulger gene: PTX3 was added
gene: PTX3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: PTX3 was set to Unknown
COVID-19 research v0.333 PDGFRA Rebecca Foulger gene: PDGFRA was added
gene: PDGFRA was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: PDGFRA was set to Unknown
COVID-19 research v0.333 NPC1 Rebecca Foulger gene: NPC1 was added
gene: NPC1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: NPC1 was set to Unknown
COVID-19 research v0.333 NLRP6 Rebecca Foulger gene: NLRP6 was added
gene: NLRP6 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: NLRP6 was set to Unknown
COVID-19 research v0.333 NECTIN1 Rebecca Foulger gene: NECTIN1 was added
gene: NECTIN1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: NECTIN1 was set to Unknown
COVID-19 research v0.333 MIR155 Rebecca Foulger gene: MIR155 was added
gene: MIR155 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: MIR155 was set to Unknown
COVID-19 research v0.333 KLF2 Rebecca Foulger gene: KLF2 was added
gene: KLF2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: KLF2 was set to Unknown
COVID-19 research v0.333 KIAA0319L Rebecca Foulger gene: KIAA0319L was added
gene: KIAA0319L was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: KIAA0319L was set to Unknown
COVID-19 research v0.333 ITGB3 Rebecca Foulger gene: ITGB3 was added
gene: ITGB3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: ITGB3 was set to Unknown
COVID-19 research v0.333 ITGAV Rebecca Foulger gene: ITGAV was added
gene: ITGAV was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: ITGAV was set to Unknown
COVID-19 research v0.333 IRF2 Rebecca Foulger gene: IRF2 was added
gene: IRF2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: IRF2 was set to Unknown
COVID-19 research v0.333 ILF3 Rebecca Foulger gene: ILF3 was added
gene: ILF3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: ILF3 was set to Unknown
COVID-19 research v0.333 IL9 Rebecca Foulger gene: IL9 was added
gene: IL9 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: IL9 was set to Unknown
COVID-19 research v0.333 IL3 Rebecca Foulger gene: IL3 was added
gene: IL3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: IL3 was set to Unknown
COVID-19 research v0.333 IFNE Rebecca Foulger gene: IFNE was added
gene: IFNE was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: IFNE was set to Unknown
COVID-19 research v0.333 IFNA1 Rebecca Foulger gene: IFNA1 was added
gene: IFNA1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: IFNA1 was set to Unknown
COVID-19 research v0.333 GPR183 Rebecca Foulger gene: GPR183 was added
gene: GPR183 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: GPR183 was set to Unknown
COVID-19 research v0.333 GPATCH3 Rebecca Foulger gene: GPATCH3 was added
gene: GPATCH3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: GPATCH3 was set to Unknown
COVID-19 research v0.333 GNAQ Rebecca Foulger gene: GNAQ was added
gene: GNAQ was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: GNAQ was set to Unknown
COVID-19 research v0.333 FOLR1 Rebecca Foulger gene: FOLR1 was added
gene: FOLR1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: FOLR1 was set to Unknown
COVID-19 research v0.333 EIF3M Rebecca Foulger gene: EIF3M was added
gene: EIF3M was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: EIF3M was set to Unknown
COVID-19 research v0.333 EGFR Rebecca Foulger gene: EGFR was added
gene: EGFR was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: EGFR was set to Unknown
COVID-19 research v0.333 DICER1 Rebecca Foulger gene: DICER1 was added
gene: DICER1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: DICER1 was set to Unknown
COVID-19 research v0.333 CXCR3 Rebecca Foulger gene: CXCR3 was added
gene: CXCR3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: CXCR3 was set to Unknown
COVID-19 research v0.333 CLDN9 Rebecca Foulger gene: CLDN9 was added
gene: CLDN9 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: CLDN9 was set to Unknown
COVID-19 research v0.333 CLDN6 Rebecca Foulger gene: CLDN6 was added
gene: CLDN6 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: CLDN6 was set to Unknown
COVID-19 research v0.333 CDKN1B Rebecca Foulger gene: CDKN1B was added
gene: CDKN1B was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: CDKN1B was set to Unknown
COVID-19 research v0.333 CD28 Rebecca Foulger gene: CD28 was added
gene: CD28 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: CD28 was set to Unknown
COVID-19 research v0.333 CD244 Rebecca Foulger gene: CD244 was added
gene: CD244 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: CD244 was set to Unknown
COVID-19 research v0.333 CD207 Rebecca Foulger gene: CD207 was added
gene: CD207 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: CD207 was set to Unknown
COVID-19 research v0.333 CCR7 Rebecca Foulger gene: CCR7 was added
gene: CCR7 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: CCR7 was set to Unknown
COVID-19 research v0.333 CCR2 Rebecca Foulger gene: CCR2 was added
gene: CCR2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: CCR2 was set to Unknown
COVID-19 research v0.333 CASP1 Rebecca Foulger gene: CASP1 was added
gene: CASP1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: CASP1 was set to Unknown
COVID-19 research v0.333 ATG5 Rebecca Foulger gene: ATG5 was added
gene: ATG5 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: ATG5 was set to Unknown
COVID-19 research v0.333 ATG16L1 Rebecca Foulger gene: ATG16L1 was added
gene: ATG16L1 was added to COVID-19 research. Sources: Expert Review Red,OMIM,Expert list
Mode of inheritance for gene: ATG16L1 was set to Unknown
COVID-19 research v0.333 ATF3 Rebecca Foulger gene: ATF3 was added
gene: ATF3 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber
Mode of inheritance for gene: ATF3 was set to Unknown
COVID-19 research v0.333 AIM2 Rebecca Foulger gene: AIM2 was added
gene: AIM2 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green
Mode of inheritance for gene: AIM2 was set to Unknown
COVID-19 research v0.332 ACE2 Catherine Snow reviewed gene: ACE2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.332 ZFHX3 Sarah Leigh edited their review of gene: ZFHX3: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 WSCD1 Sarah Leigh edited their review of gene: WSCD1: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 UNC5CL Sarah Leigh edited their review of gene: UNC5CL: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 TAPT1 Sarah Leigh edited their review of gene: TAPT1: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 SPNS3 Sarah Leigh edited their review of gene: SPNS3: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 RPAIN Sarah Leigh edited their review of gene: RPAIN: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 PROM1 Sarah Leigh edited their review of gene: PROM1: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 PKD1L3 Sarah Leigh edited their review of gene: PKD1L3: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 NUP88 Sarah Leigh edited their review of gene: NUP88: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 MLKL Sarah Leigh edited their review of gene: MLKL: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 MIS12 Sarah Leigh edited their review of gene: MIS12: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 LDB2 Sarah Leigh edited their review of gene: LDB2: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 KARS Sarah Leigh edited their review of gene: KARS: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 HYDIN Sarah Leigh edited their review of gene: HYDIN: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 CC2D2A Sarah Leigh edited their review of gene: CC2D2A: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.332 BCAR1 Sarah Leigh edited their review of gene: BCAR1: Added comment: Using Collaborative Cross mouse genetic reference population, PMID 32348764 studied the genetic regulation of variation in antibody response to influenza A virus (IAV) infection. This enabled the identification of 23 quantitative trait loci (QTL) associated with variation in specific antibody isotypes across time points; this allowed a subset to be found that broadly affect the antibody response to IAV as well as other viruses. This gene is the equivalent human for the mouse gene that was classified as a candidate from one of the QTLs, based on the predicted variant consequences and haplotype-specific expression patterns (PMID 32348764 table 2).; Changed mode of inheritance: Unknown
COVID-19 research v0.331 TMPRSS2 Catherine Snow Mode of inheritance for gene: TMPRSS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
COVID-19 research v0.330 CD14 Catherine Snow Mode of inheritance for gene: CD14 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
COVID-19 research v0.329 CASP3 Catherine Snow Mode of inheritance for gene: CASP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
COVID-19 research v0.328 BLK Catherine Snow Mode of inheritance for gene: BLK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
COVID-19 research v0.327 BLK Catherine Snow edited their review of gene: BLK: Changed mode of inheritance: Unknown
COVID-19 research v0.327 APOE Eleanor Williams changed review comment from: PMID: 32451547 - Kuo et al 2020 - Using UK biobank data they found that the ApoE e4 allele ( rs429358) increases risks of being hospitalized with COVID-19, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes. ApoE e4 allele frequency is higher in people of African ancestry than in Europeans, and
preliminary results suggest that ApoE e4 prevalence makes a modest contribution to the excess incidence of COVID-19 in Blacks. (Originially added to the panel as preprint: https://doi.org/10.1101/2020.05.07.20094409)
Sources: Literature; to: PMID: 32451547 - Kuo et al 2020 - Using UK biobank data they found that the ApoE e4 allele ( rs429358) increases risks of being hospitalized with COVID-19, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes. ApoE e4e4 homozygotes were more likely to be COVID-19 test positives compared to e3e3 homozygotes. ApoE e4 allele frequency is higher in people of African ancestry than in Europeans, and preliminary results suggest that ApoE e4 prevalence makes a modest contribution to the excess incidence of COVID-19 in Blacks. (Originially added to the panel as preprint: https://doi.org/10.1101/2020.05.07.20094409)
Sources: Literature

COVID-19 research v0.327 APOE Eleanor Williams Publications for gene: APOE were set to https://doi.org/10.1101/2020.05.07.20094409
COVID-19 research v0.326 APOE Eleanor Williams changed review comment from: Preprint: https://doi.org/10.1101/2020.05.07.20094409 Kuo et al 2020 - Using UK biobank data they found that the ApoE e4 allele ( rs429358) increases risks of being hospitalized with COVID-19, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes.
ApoE e4 allele frequency is higher in people of African ancestry than in Europeans, and
preliminary results suggest that ApoE e4 prevalence makes a modest contribution to the
excess incidence of COVID-19 in Blacks.
Sources: Literature; to: PMID: 32451547 - Kuo et al 2020 - Using UK biobank data they found that the ApoE e4 allele ( rs429358) increases risks of being hospitalized with COVID-19, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes. ApoE e4 allele frequency is higher in people of African ancestry than in Europeans, and
preliminary results suggest that ApoE e4 prevalence makes a modest contribution to the excess incidence of COVID-19 in Blacks. (Originially added to the panel as preprint: https://doi.org/10.1101/2020.05.07.20094409)
Sources: Literature
COVID-19 research v0.326 ABO Catherine Snow Mode of inheritance for gene: ABO was changed from Other to Unknown
COVID-19 research v0.325 SLAMF6 Catherine Snow gene: SLAMF6 was added
gene: SLAMF6 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLAMF6 was set to Unknown
Publications for gene: SLAMF6 were set to 30366106
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SLAMF6.

Natural cytotoxicity receptors, such as NKp46, NKp44, and NKp30 (NCR3), are selectively expressed on NK cells and cooperate in the induction of NK cell activity

Yigit et al (2019) summarised research in "SLAMF6 in health and disease: Implications for therapeutic targeting"
Sources: Expert list
COVID-19 research v0.324 SIGIRR Catherine Snow changed review comment from: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SIGIRR.

Molgora et al. (2017) reported that IL-1R8 serves as a checkpoint for natural killer (NK) cell maturation and effector function. Its genetic blockade unleashes NK cell-mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis, and cytomegalovirus infection
Sources: Expert list; to: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SIGIRR.

Molgora et al. (2017) reported that IL-1R8 serves as a checkpoint for natural killer (NK) cell maturation and effector function. Its genetic blockade unleashes NK cell-mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis, and cytomegalovirus infection

Li et al. (2019) who worked with mice. Found that stabilization of Sigirr by USP13 describes a novel anti-inflammatory pathway in diseases that could provide a new strategy to modulate immune activation.
Sources: Expert list
COVID-19 research v0.324 SIGIRR Catherine Snow Publications for gene: SIGIRR were set to 29072292
COVID-19 research v0.323 SIGIRR Catherine Snow gene: SIGIRR was added
gene: SIGIRR was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SIGIRR was set to Unknown
Publications for gene: SIGIRR were set to 29072292
Review for gene: SIGIRR was set to RED
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SIGIRR.

Molgora et al. (2017) reported that IL-1R8 serves as a checkpoint for natural killer (NK) cell maturation and effector function. Its genetic blockade unleashes NK cell-mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis, and cytomegalovirus infection
Sources: Expert list
COVID-19 research v0.322 SLC11A1 Catherine Snow gene: SLC11A1 was added
gene: SLC11A1 was added to COVID-19 research. Sources: Literature,Expert list
Mode of inheritance for gene: SLC11A1 was set to Unknown
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SLC11A1

Multiple association studies with TB only, no viral associations
Sources: Literature, Expert list
COVID-19 research v0.321 SLC2A1 Ivone Leong Classified gene: SLC2A1 as Amber List (moderate evidence)
COVID-19 research v0.321 SLC2A1 Ivone Leong Gene: slc2a1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.320 SLC2A1 Ivone Leong gene: SLC2A1 was added
gene: SLC2A1 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLC2A1 was set to Unknown
Publications for gene: SLC2A1 were set to 15767416; 22308487
Review for gene: SLC2A1 was set to AMBER
Added comment: GLUT1 is a receptor for HTLV and suggested that perturbations in glucose metabolism resulting from interactions of HTLV envelope glycoproteins with GLUT1 are likely to contribute to HTLV-associated disorders (PMID: 15767416).

PMID: 22308487 shows that IL-7 induced upregulation of Glut1 changes glucos uptake and causes T lymphocyptes susceptible to HIV-1 infection.
Sources: Expert list
COVID-19 research v0.319 STAT6 Ivone Leong gene: STAT6 was added
gene: STAT6 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: STAT6 was set to Unknown
Publications for gene: STAT6 were set to 22000020; 21762972
Review for gene: STAT6 was set to RED
Added comment: Immune system gene: STAT6 mediates immune signaling in response to cytokines at the plasma membrane and to virus infection at the endoplasmic reticulum. Mice lacking Stat6 were susceptible to virus infection. Chen et al. (2011) (PMID: 22000020).

PMID: 21762972 found that STAT6 increases viral replication in the skin of patients with atopic dermatitis (chronic inflammatory skin disease) with a history of eczema herpeticum.
Sources: Expert list
COVID-19 research v0.318 TBX21 Ivone Leong Classified gene: TBX21 as Amber List (moderate evidence)
COVID-19 research v0.318 TBX21 Ivone Leong Gene: tbx21 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.317 TBX21 Ivone Leong gene: TBX21 was added
gene: TBX21 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: TBX21 was set to Unknown
Publications for gene: TBX21 were set to 15806396; 17378728; 19473434; 29399747
Phenotypes for gene: TBX21 were set to {Asthma, aspirin-induced, susceptibility to}, 208550; susceptibility to chronic HBV and HCV infection
Review for gene: TBX21 was set to AMBER
Added comment: TBX21 is a Th1-specific T-box transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (PMID: 15806396).

PMID: 17378728 found that variations at allele -1499 and haplotype D (--/AC) in the TBX21 promoter region contribute to susceptibility to HBV infection in the Chinese population.

PMID: 19473434 found that T-1993C polymorphism in the TBX21 promoter influences susceptibility to persistent HBV infection.

PMID: 29399747 found that rs4794067 (T-1993C) is significantly correlated with increased risk of HCV chronic infection (dominant model: OR = 5.690, 95% CI = 2.024-16.000) and susceptibility (dominant model: OR = 5.658, 95% CI = 2.514-12.735).
Sources: Expert list
COVID-19 research v0.316 ZNF34 Sarah Leigh Deleted their comment
COVID-19 research v0.316 ZFP36 Sarah Leigh Deleted their comment
COVID-19 research v0.316 ZC3HC1 Sarah Leigh Deleted their comment
COVID-19 research v0.316 TUBGCP3 Sarah Leigh Deleted their comment
COVID-19 research v0.316 TSPAN14 Sarah Leigh Deleted their comment
COVID-19 research v0.316 TNIP1 Sarah Leigh Deleted their comment
COVID-19 research v0.316 SLC13A4 Sarah Leigh Deleted their comment
COVID-19 research v0.316 ODC1 Sarah Leigh Deleted their comment
COVID-19 research v0.316 MTPAP Sarah Leigh Deleted their comment
COVID-19 research v0.316 MICA Sarah Leigh Deleted their comment
COVID-19 research v0.316 MED13L Sarah Leigh Deleted their comment
COVID-19 research v0.316 IVNS1ABP Sarah Leigh Deleted their comment
COVID-19 research v0.316 FOXM1 Sarah Leigh Deleted their comment
COVID-19 research v0.316 FBRS Sarah Leigh Deleted their comment
COVID-19 research v0.316 CXorf36 Sarah Leigh Deleted their comment
COVID-19 research v0.316 ABI3 Sarah Leigh Deleted their comment
COVID-19 research v0.316 STK17B Ivone Leong gene: STK17B was added
gene: STK17B was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: STK17B was set to Unknown
Publications for gene: STK17B were set to 19017949; 19017948; 17364498; 17966037
Review for gene: STK17B was set to RED
Added comment: Drak2 -/- mice were susceptible to other models of autoimmunity and were normally resistant to acute viral infection.
Sources: Expert list
COVID-19 research v0.315 ZNF34 Sarah Leigh commented on gene: ZNF34: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 ZFP36 Sarah Leigh commented on gene: ZFP36: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 ZC3HC1 Sarah Leigh commented on gene: ZC3HC1: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 TUBGCP3 Sarah Leigh commented on gene: TUBGCP3: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 TSPAN14 Sarah Leigh commented on gene: TSPAN14: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 TNIP1 Sarah Leigh commented on gene: TNIP1: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 SLC13A4 Sarah Leigh commented on gene: SLC13A4: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 ODC1 Sarah Leigh commented on gene: ODC1: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 MTPAP Sarah Leigh commented on gene: MTPAP: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 MICA Sarah Leigh commented on gene: MICA: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 MED13L Sarah Leigh commented on gene: MED13L: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 IVNS1ABP Sarah Leigh commented on gene: IVNS1ABP: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 FOXM1 Sarah Leigh commented on gene: FOXM1: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 FBRS Sarah Leigh commented on gene: FBRS: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.315 CXorf36 Sarah Leigh commented on gene: CXorf36: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988). New gene name DIPK2B
COVID-19 research v0.315 ABI3 Sarah Leigh commented on gene: ABI3: One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).
COVID-19 research v0.314 SLFN12L Ivone Leong gene: SLFN12L was added
gene: SLFN12L was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLFN12L was set to Unknown
Review for gene: SLFN12L was set to RED
Added comment: Mouse model-Immune system. Mice homozygous for the Slfn2 elektra mutation exhibited enhanced susceptibility to bacterial and viral infections and diminished numbers of T cells and inflammatory monocytes that failed to proliferate after infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. Slfn2 homologous to SFLN12 and SLFN12L
Sources: Expert list
COVID-19 research v0.313 SLFN12 Ivone Leong gene: SLFN12 was added
gene: SLFN12 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLFN12 was set to Unknown
Review for gene: SLFN12 was set to RED
Added comment: Mouse model-Immune system. Mice homozygous for the Slfn2 elektra mutation exhibited enhanced susceptibility to bacterial and viral infections and diminished numbers of T cells and inflammatory monocytes that failed to proliferate after infection and died via the intrinsic apoptotic pathway in response to diverse proliferative stimuli. Slfn2 homologous to SFLN12 and SLFN12L
Sources: Expert list
COVID-19 research v0.312 SLC20A2 Ivone Leong gene: SLC20A2 was added
gene: SLC20A2 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLC20A2 was set to Unknown
Review for gene: SLC20A2 was set to RED
Added comment: GLVR2 is a receptor for amphotropic virus. Non-human viruses listed.
Sources: Expert list
COVID-19 research v0.311 SERINC5 Catherine Snow changed review comment from: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SERINC5

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3 inhibited infectivity of human immunodeficiency virus (HIV)-1 and murine leukemia retrovirus (MLV)
Sudderuddin et al (2020) found that SERINC5 on the cell surface is down regulated upon HIV infection
Sources: Literature; to: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SERINC5.

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3 inhibited infectivity of human immunodeficiency virus (HIV)-1 and murine leukemia retrovirus (MLV)
Sudderuddin et al (2020) found that SERINC5 on the cell surface is down regulated upon HIV infection
Sources: Literature
COVID-19 research v0.311 SERINC5 Catherine Snow Classified gene: SERINC5 as Amber List (moderate evidence)
COVID-19 research v0.311 SERINC5 Catherine Snow Gene: serinc5 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.310 SERINC5 Catherine Snow gene: SERINC5 was added
gene: SERINC5 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SERINC5 was set to Unknown
Publications for gene: SERINC5 were set to 26416734; 31918727
Review for gene: SERINC5 was set to AMBER
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".

Currently no gene disease association for SERINC5

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3 inhibited infectivity of human immunodeficiency virus (HIV)-1 and murine leukemia retrovirus (MLV)
Sudderuddin et al (2020) found that SERINC5 on the cell surface is down regulated upon HIV infection
Sources: Literature
COVID-19 research v0.309 SERINC3 Catherine Snow Publications for gene: SERINC3 were set to
COVID-19 research v0.308 SERINC3 Catherine Snow changed review comment from: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
No current gene disease relationship in OMIM.
The human immunodeficiency virus (HIV)-1 Nef protein and the unrelated murine leukemia virus (MLV) glycosylated Gag (glycoGag) protein enhance HIV-1 infectivity. Usami et al. (2015) found that silencing both SERINC3 and SERINC5 (614551) precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. CD4-positive T cells lacking both SERINC3 and SERINC5 showed significantly increased susceptibility to Nef-deficient virions. SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. Usami et al. (2015) proposed that inhibiting Nef-mediated downregulation of SERINC3 and SERINC5, which are normally highly expressed in HIV-1 target cells, has the potential to combat HIV/AIDS.

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3 (607165), inhibited infectivity of human immunodeficiency virus (HIV)-1 (see 609423) and murine leukemia retrovirus (MLV)
Sources: Literature; to: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
No current gene disease relationship in OMIM.
The human immunodeficiency virus (HIV)-1 Nef protein and the unrelated murine leukemia virus (MLV) glycosylated Gag (glycoGag) protein enhance HIV-1 infectivity. Usami et al. (2015) found that silencing both SERINC3 and SERINC5 (614551) precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. CD4-positive T cells lacking both SERINC3 and SERINC5 showed significantly increased susceptibility to Nef-deficient virions. SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. Usami et al. (2015) proposed that inhibiting Nef-mediated downregulation of SERINC3 and SERINC5, which are normally highly expressed in HIV-1 target cells, has the potential to combat HIV/AIDS.

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3, inhibited infectivity of human immunodeficiency virus (HIV)-1 and murine leukemia retrovirus (MLV)
Sources: Literature
COVID-19 research v0.308 SERINC3 Catherine Snow Classified gene: SERINC3 as Amber List (moderate evidence)
COVID-19 research v0.308 SERINC3 Catherine Snow Gene: serinc3 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.307 SERINC3 Catherine Snow changed review comment from: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
No current gene disease relationship in OMIM.
The human immunodeficiency virus (HIV)-1 Nef protein and the unrelated murine leukemia virus (MLV) glycosylated Gag (glycoGag) protein enhance HIV-1 infectivity. Usami et al. (2015) found that silencing both SERINC3 and SERINC5 (614551) precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. CD4-positive T cells lacking both SERINC3 and SERINC5 showed significantly increased susceptibility to Nef-deficient virions. SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. Usami et al. (2015) proposed that inhibiting Nef-mediated downregulation of SERINC3 and SERINC5, which are normally highly expressed in HIV-1 target cells, has the potential to combat HIV/AIDS.
Sources: Literature; to: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
No current gene disease relationship in OMIM.
The human immunodeficiency virus (HIV)-1 Nef protein and the unrelated murine leukemia virus (MLV) glycosylated Gag (glycoGag) protein enhance HIV-1 infectivity. Usami et al. (2015) found that silencing both SERINC3 and SERINC5 (614551) precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. CD4-positive T cells lacking both SERINC3 and SERINC5 showed significantly increased susceptibility to Nef-deficient virions. SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. Usami et al. (2015) proposed that inhibiting Nef-mediated downregulation of SERINC3 and SERINC5, which are normally highly expressed in HIV-1 target cells, has the potential to combat HIV/AIDS.

Screening human cell lines and using CRISPR-Cas9 analysis, Rosa et al. (2015) found that SERINC5, and to a lesser extent SERINC3 (607165), inhibited infectivity of human immunodeficiency virus (HIV)-1 (see 609423) and murine leukemia retrovirus (MLV)
Sources: Literature
COVID-19 research v0.307 SERINC3 Catherine Snow gene: SERINC3 was added
gene: SERINC3 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SERINC3 was set to Unknown
Review for gene: SERINC3 was set to AMBER
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
No current gene disease relationship in OMIM.
The human immunodeficiency virus (HIV)-1 Nef protein and the unrelated murine leukemia virus (MLV) glycosylated Gag (glycoGag) protein enhance HIV-1 infectivity. Usami et al. (2015) found that silencing both SERINC3 and SERINC5 (614551) precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. CD4-positive T cells lacking both SERINC3 and SERINC5 showed significantly increased susceptibility to Nef-deficient virions. SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. Usami et al. (2015) proposed that inhibiting Nef-mediated downregulation of SERINC3 and SERINC5, which are normally highly expressed in HIV-1 target cells, has the potential to combat HIV/AIDS.
Sources: Literature
COVID-19 research v0.306 SDC1 Catherine Snow gene: SDC1 was added
gene: SDC1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SDC1 was set to Unknown
Publications for gene: SDC1 were set to 12530973
Review for gene: SDC1 was set to RED
Added comment: Curation by Illumina clinical curators contributing to Covid-19 effort. Curation on all OMIM genes which hit the term "virus".
NO gene disease association for SDC1. Bobardt et al. (2003) suggested that SDC-rich endothelial cells lining the vasculature can provide a microenvironment that boosts HIV replication in T cells.
Sources: Literature
COVID-19 research v0.305 SCN4A Catherine Snow changed review comment from: No further evidence since. Matthews et al. (2011) reported a family with PMC due to the heterozygous T1313M mutation. Before correct diagnosis, the youngest affected individual presented with neonatal inspiratory stridor and poor feeding. Laryngoscopy showed findings consistent with laryngomalacia. He continued to have stridor for the first 6 months of life, and later motor milestones were mildly delayed. In early childhood, he was noted to have frequent episodic muscle weakness and stiffness associated with cold weather. At age 4 years, he continued to have episodes of inspiratory stridor exacerbated by viral illness, cold weather, and prolonged laughing or crying. His mother, grandfather, and great-uncle reported similar episodes of muscle stiffness and weakness exacerbated by cold and exercise.
Sources: Literature; to: No further evidence reported since. Matthews et al. (2011) PMID 21220685 reported a family with PMC due to the heterozygous T1313M mutation. Before correct diagnosis, the youngest affected individual presented with neonatal inspiratory stridor and poor feeding. Laryngoscopy showed findings consistent with laryngomalacia. He continued to have stridor for the first 6 months of life, and later motor milestones were mildly delayed. In early childhood, he was noted to have frequent episodic muscle weakness and stiffness associated with cold weather. At age 4 years, he continued to have episodes of inspiratory stridor exacerbated by viral illness, cold weather, and prolonged laughing or crying. His mother, grandfather, and great-uncle reported similar episodes of muscle stiffness and weakness exacerbated by cold and exercise.
Sources: Literature
COVID-19 research v0.305 SCN4A Catherine Snow gene: SCN4A was added
gene: SCN4A was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SCN4A was set to Unknown
Publications for gene: SCN4A were set to 21220685
Review for gene: SCN4A was set to RED
Added comment: No further evidence since. Matthews et al. (2011) reported a family with PMC due to the heterozygous T1313M mutation. Before correct diagnosis, the youngest affected individual presented with neonatal inspiratory stridor and poor feeding. Laryngoscopy showed findings consistent with laryngomalacia. He continued to have stridor for the first 6 months of life, and later motor milestones were mildly delayed. In early childhood, he was noted to have frequent episodic muscle weakness and stiffness associated with cold weather. At age 4 years, he continued to have episodes of inspiratory stridor exacerbated by viral illness, cold weather, and prolonged laughing or crying. His mother, grandfather, and great-uncle reported similar episodes of muscle stiffness and weakness exacerbated by cold and exercise.
Sources: Literature
COVID-19 research v0.304 TMPRSS2 Eleanor Williams reviewed gene: TMPRSS2: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.15.098616; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.304 SLC6A19 Eleanor Williams gene: SLC6A19 was added
gene: SLC6A19 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SLC6A19 was set to Unknown
Added comment: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients.
Sources: Literature
COVID-19 research v0.303 ACE2 Eleanor Williams changed review comment from: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural
Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2.; to: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2.
COVID-19 research v0.303 ACE2 Eleanor Williams edited their review of gene: ACE2: Added comment: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural
Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2.; Changed publications: 32015507, https://doi.org/10.1101/2020.05.15.098616
COVID-19 research v0.303 TMPRSS4 Eleanor Williams gene: TMPRSS4 was added
gene: TMPRSS4 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: TMPRSS4 was set to Unknown
Publications for gene: TMPRSS4 were set to https://doi.org/10.1101/2020.05.12.091314
Added comment: Preprint: Wruck and Adjaye https://doi.org/10.1101/2020.05.12.091314 - describe a meta-analysis focussing on the transcriptome data from human lung epithelial cells including samples infected with SARS-CoV-2 from a study described by Blanco Melo et al.12. The exploration was directed to co-expression with the known CoV-2 receptor ACE2. 72 genes significantly co-expressed with ACE2. Of the transmembrane serine proteases, the most significantly coexpressed with ACE2 was TMPRSS4, suggesting it to be a putative druggable target.
Pathway analysis revealed papilloma virus infection amongst the most significantly correlated pathways.
Sources: Literature
COVID-19 research v0.302 MBL2 Eleanor Williams commented on gene: MBL2
COVID-19 research v0.302 OAS1 Eleanor Williams reviewed gene: OAS1: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.13.093690; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.302 TMPRSS11A Eleanor Williams gene: TMPRSS11A was added
gene: TMPRSS11A was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: TMPRSS11A was set to Unknown
Publications for gene: TMPRSS11A were set to https://doi.org/10.1101/2020.05.13.093690
Review for gene: TMPRSS11A was set to RED
Added comment: Preprint: Klaassen et al https://doi.org/10.1101/2020.05.13.093690 - performed analysis of variants in FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population and identified 22 variants with potential functional effect. Then used in-silico prediction and comparative population analysis and found 2 rare variants p.Lys48Arg and p.Arg328Gln. For both of these variants, PolyPhen-2, SIFT and MutPred2
algorithms predict benign/tolerated effect but the protein structure of TMPRSS11a is not well known.
Sources: Literature
COVID-19 research v0.301 PRSS1 Eleanor Williams gene: PRSS1 was added
gene: PRSS1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: PRSS1 was set to Unknown
Publications for gene: PRSS1 were set to https://doi.org/10.1101/2020.05.13.093690
Added comment: Preprint: Klaassen et al https://doi.org/10.1101/2020.05.13.093690 - performed analysis of variants in FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population and identified 22 variants with potential functional effect. Then used in-silico prediction and comparative population analysis and found two rare variants in the PRSS1 gene, c.592-8C>T and p.Asn54Lys. Variant c.592-8C>T was previously detected
in patients with cystic fibrosis presenting with chronic pancreatitis and p.Asn54Lys is predicted to be possibly damaging.
Sources: Literature
COVID-19 research v0.300 PLG Eleanor Williams gene: PLG was added
gene: PLG was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: PLG was set to Unknown
Publications for gene: PLG were set to https://doi.org/10.1101/2020.05.13.093690
Review for gene: PLG was set to RED
Added comment: Preprint: Klaassen et al https://doi.org/10.1101/2020.05.13.093690 - performed analysis of variants in FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population and identified 22 variants with potential functional effect. Then used in-silico prediction and comparative population analysis and found 6 rare variants in PLG. p.Arg261His and p.Ala494Val are predicted to be probably damaging/deleterious.
Sources: Literature
COVID-19 research v0.299 FURIN Eleanor Williams commented on gene: FURIN: Preprint: Klaassen et al https://doi.org/10.1101/2020.05.13.093690 - performed analysis of variants in FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population and identified 22 variants with potential functional effect. Then used in-silico prediction and comparative population analysis and found two rare variants in FURIN p.Thr33Ala and p.Gly146Ser. p.Gly146Ser. is predicted to be deleterious and may change its ability
to cleave furin-like sites in the S protein of the SARS-CoV-2.
COVID-19 research v0.299 ACE2 Eleanor Williams changed review comment from: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2-
RBD complexes of different species allowing us to anticipate the effects of amino acid sequence
variation of ACE2 on viral entry; to: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2-RBD complexes of different species allowing us to anticipate the effects of amino acid sequence variation of ACE2 on viral entry
COVID-19 research v0.299 ACE2 Eleanor Williams commented on gene: ACE2: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2-
RBD complexes of different species allowing us to anticipate the effects of amino acid sequence
variation of ACE2 on viral entry
COVID-19 research v0.299 MUC5B Eleanor Williams edited their review of gene: MUC5B: Changed publications: https://doi.org/10.1101/2020.05.12.20099333
COVID-19 research v0.299 MUC5B Eleanor Williams gene: MUC5B was added
gene: MUC5B was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MUC5B was set to Unknown
Review for gene: MUC5B was set to RED
Added comment: Preprint: van Moorsel et al https://doi.org/10.1101/2020.05.12.20099333 The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. They compared patients with severe COVID-19 to controls and found the MUC5B rs35705950 promoter polymorphism associates with COVID-19. The risk allele (T) for idiopathic pulmonary fibrosis (IPF) is protective against the development of severe COVID-19 disease.
Sources: Literature
COVID-19 research v0.298 ACE2 Eleanor Williams commented on gene: ACE2: Preprint: https://doi.org/10.1101/2020.05.12.20098160 - Shovlin and Vizcaychip - variants in 213,158 exomes/genomes were integrated for ACE2 . ACMG/AMP-based pathogenicity criteria were applied. Modelling the ″COVID-resistant ″ state where pathogenic alleles would be beneficial, nine null alleles met PVS1. Thirty-seven variants met PM1 based on critical location +/-PP3 based on computational modelling. Modelling a ″COVID-susceptible ″ state, 31 variants in four upstream open reading frames and 5′ untranslated regions could meet PM1, and may have differential effects if aminoglycoside antibiotics were prescribed for pneumonia and sepsis.
COVID-19 research v0.298 SCARB1 Eleanor Williams Classified gene: SCARB1 as Amber List (moderate evidence)
COVID-19 research v0.298 SCARB1 Eleanor Williams Added comment: Comment on list classification: Rating Amber as there is some evidence that variants in this gene are associated with response to Hepatitus C virus
COVID-19 research v0.298 SCARB1 Eleanor Williams Gene: scarb1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.297 SCARB1 Eleanor Williams edited their review of gene: SCARB1: Changed publications: 12356718, 28827115, 29715527
COVID-19 research v0.297 SCARB1 Eleanor Williams gene: SCARB1 was added
gene: SCARB1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SCARB1 was set to Unknown
Added comment: Not associated with any relevant disease phenotype in OMIM. SCARB1 is also known as SRB1

PMID: 12356718 - Scarselli et al 2002 - Characterization of hepatitis C virus (HCV) envelope glycoprotein E2 binding after chemical or enzymic modification of the cell surface led to the identification of the scavenger receptor type B class I (SR-BI) as the E2 receptor on HepG2 cells.

PMID: 28827115 - Sadeghi et al 2017 - SCARB1 rs10846744 (CC) genotype (P=0.001) was strongly associated with sustained virological response

PMID: 28363797 - Westhaus et al 2018 - Non-synonymous variants: S112F and T175A have greatly reduced Hepatitus C virus (HCV) receptor function. When present on the cell surface, these variants are impaired in their ability to interact with HCV E2. Non-coding variants: The G allele in rs3782287 is associated with decreased viral load.

PMID: 29715527 - Naffari et al 2018 -looked at treatment responses in 395 treatment-naïve patients with chronic Hepatitus C Virus (CHC) genotype 1 treated with pegylated interferon-α and ribavirin. Rapid virologic response (RVR), complete early virologic response (cEVR) , and sustained virologic responseSVR were significantly associated with SCARB1 rs10846744 (CC).
Sources: Literature
COVID-19 research v0.296 PYCARD Eleanor Williams gene: PYCARD was added
gene: PYCARD was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: PYCARD was set to Unknown
Publications for gene: PYCARD were set to 18288107
Review for gene: PYCARD was set to RED
Added comment: Not associated with a disease phenotype in OMIM.

PYCARD is also known as ASC

PMID: 18288107 Muruve et al. 2008 - internalized adenoviral DNA induces maturation of pro-IL1B in macrophages, which is dependent on NALP3 and ASC, components of the innate cytosolic molecular complex termed the inflammasome. ASC-deficient mice display reduced innate inflammatory responses to adenovirus particles.
Sources: Literature
COVID-19 research v0.295 PQBP1 Eleanor Williams gene: PQBP1 was added
gene: PQBP1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: PQBP1 was set to Unknown
Publications for gene: PQBP1 were set to 26046437
Review for gene: PQBP1 was set to RED
Added comment: Not associated with a viral susceptibility phenotype in OMIM.

PMID: 26046437 - Yoh et al 2015 - found PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response
Sources: Literature
COVID-19 research v0.294 OCLN Eleanor Williams gene: OCLN was added
gene: OCLN was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: OCLN was set to Unknown
Publications for gene: OCLN were set to 19182773; 31328852
Review for gene: OCLN was set to RED
Added comment: Not associated with any viral susceptibility phenotypes in OMIM.

Evidence that OCLN is involved in HCV cell entry

PMID: 19182773 - Ploss et al 2009 - show that human occludin is an essential HCV cell entry factor that is able to render murine cells infectable with HCVpp. Similarly, OCLN is required for the HCV-susceptibility of human cells, because its overexpression in uninfectable cells specifically enhanced HCVpp uptake, whereas its silencing in permissive cells impaired both HCVpp and HCVcc infection.

PMID: 31328852 - Lavie et al 2019 - looked at which residues in OCLN affect hepatitis C virus (HCV) entry. In the context of full-length OCLN, mutation of I279 and W281 residues only partially affected infection and cell surface localization.
Sources: Literature
COVID-19 research v0.293 NRP2 Eleanor Williams gene: NRP2 was added
gene: NRP2 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: NRP2 was set to Unknown
Publications for gene: NRP2 were set to 30057110; 29120745
Review for gene: NRP2 was set to RED
Added comment: Not associated with a disease phenotype in OMIM or Gene2Phenotype.

PMID: 30057110: Martinez-Martin et al. (2018) identified NRP2 as a host receptor for human cytomegalovirus (HCMV) pentamer.

PMID: 29120745 -Raaben et al 2017 - A genome-wide haploid genetic screen identified the transmembrane protein neuropilin 2 (NRP2) and tetraspanin CD63 as factors for Lujo virus (LUJV) glycoprotein-mediated infection. Overexpression of NRP2 or its N-terminal domain enhances VSV-LUJV infection, and cells lacking NRP2 are deficient in wild-type LUJV infection.
Sources: Literature
COVID-19 research v0.292 NCR3 Eleanor Williams gene: NCR3 was added
gene: NCR3 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: NCR3 was set to Unknown
Publications for gene: NCR3 were set to 26094914; 24845613; 30325780
Phenotypes for gene: NCR3 were set to {Malaria, mild, susceptibility to}, 609148
Review for gene: NCR3 was set to RED
Added comment: Associated with {Malaria, mild, susceptibility to} #609148 in OMIM. It is also known as NKp30.

Evidence that level of NCR3/NKp30 expression is reduced in those infected with virus, and increased in those who remain uninfected. No reports that SNVs in the NCR3 gene affect suceptibility to viral infection.

PMID: 26094914 - Mantovani et al 2015 - six different splice variants of the NKp30-encoding gene NCR3, which are known to be expressed on the cell surface. NKp30 receptor expression on NK cells and all isoforms were reduced in chronic hepatitis C virus(HCV)-infected patients.

PMID: 24845613 - Sugden et al 2014 - enhanced expression of NKp30 on NK cells resulted in protection from developing HCV infection in multiply exposed uninfected individuals

PMID: 30325780 - Lucar et al 2019 - report in HIV-2 patients a very significant reduced expression of the activating NKp30 receptor on NK cells.
Sources: Literature
COVID-19 research v0.291 MYH9 Eleanor Williams commented on gene: MYH9: Not associated with any relevant phenotypes in OMIM.
COVID-19 research v0.291 MYH9 Eleanor Williams edited their review of gene: MYH9: Changed rating: RED
COVID-19 research v0.291 MYH9 Eleanor Williams gene: MYH9 was added
gene: MYH9 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MYH9 was set to Unknown
Publications for gene: MYH9 were set to 20944748; 27112594; 31649651; 29879459
Review for gene: MYH9 was set to AMBER
Added comment: PMID: 20944748 - Arii et al. (2010) showed that nonmuscle myosin heavy chain IIA (NMHC-IIA), a subunit of nonmuscle myosin IIA (NM-IIA), functions as a herpes simplex virus-1 (HSV-1) entry receptor by interacting with glycoprotein B.

PMID: 27112594 - Gao et al (2016) report the identification of non-muscle myosin heavy chain 9 (MYH9) as an essential factor for PRRSV infection

Several other papers describing the role of MYH9 with porcine reproductive and respiratory syndrome virus invasion e.g. 31649651;29879459
Sources: Literature
COVID-19 research v0.290 MTOR Rebecca Foulger Classified gene: MTOR as Red List (low evidence)
COVID-19 research v0.290 MTOR Rebecca Foulger Added comment: Comment on list classification: A number of papers provide evidence that some viruses use mTOR signaling to promote their replication (e.g. PMID:28953980), and how inhibition of PI3K/TOR signaling inhibits viral replication (e.g. PMID:29475942). No variant studies on TOR so Red rating appropriate for now.
COVID-19 research v0.290 MTOR Rebecca Foulger Gene: mtor has been classified as Red List (Low Evidence).
COVID-19 research v0.289 MTOR Rebecca Foulger commented on gene: MTOR: PMID:19543266. Araki et al. (2009) demonstrated that mTOR is a major regulator of memory CD8 T-cell differentiation. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced the quantity and quality of virus-specific CD8 T cells. Rapamycin treatment also enhanced memory T-cell responses in nonhuman primates following vaccination with modified vaccinia virus Ankara.
COVID-19 research v0.289 MTOR Rebecca Foulger Phenotypes for gene: MTOR were changed from 19543266 to 19543266; 29475942; 28953980
COVID-19 research v0.288 MTOR Rebecca Foulger gene: MTOR was added
gene: MTOR was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: MTOR was set to Unknown
Phenotypes for gene: MTOR were set to 19543266
Added comment: MTOR was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel as Red. Notes from Julie Taylor and Alison Coffey (Illumina): mTOR is a major regulator of memory CD8 T-cell differentiation.
Sources: Other
COVID-19 research v0.287 MST1R Rebecca Foulger Classified gene: MST1R as Red List (low evidence)
COVID-19 research v0.287 MST1R Rebecca Foulger Added comment: Comment on list classification: Kept rating as Red for now: Possible involvement in viral-induced carcinomas, but most evidence for a role in the viral life cycle comes from animal models.
COVID-19 research v0.287 MST1R Rebecca Foulger Gene: mst1r has been classified as Red List (Low Evidence).
COVID-19 research v0.286 MST1R Rebecca Foulger Added comment: Comment on publications: Note that in the literature, MST1R is often referred to as RON for the human and Stk for the rodent orthologs.
COVID-19 research v0.286 MST1R Rebecca Foulger Publications for gene: MST1R were set to 15557181; 22974584; 16527351
COVID-19 research v0.285 MST1R Rebecca Foulger commented on gene: MST1R: PMID:22974584 Chou et al., 2012 demonstrate involvement of MST1R (RON) in Epstein-Barr virus (EBV)-associated Nasopharyngeal carcinoma (NPC).
COVID-19 research v0.285 MST1R Rebecca Foulger commented on gene: MST1R: PMID:15557181. Lee et al. (2004) proposed that HIV-1 may directly or indirectly target MST1R (RON) to disrupt normal signals that actively suppress inflammation to assure a microenvironment favorable for virus replication.
COVID-19 research v0.285 MST1R Rebecca Foulger Publications for gene: MST1R were set to
COVID-19 research v0.284 MST1R Rebecca Foulger gene: MST1R was added
gene: MST1R was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: MST1R was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MST1R were set to {Nasopharyngeal carcinoma, susceptibility to, 3}, 617075
Added comment: MST1R was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel as Red.
Sources: Other
COVID-19 research v0.283 MRC1 Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Red to Amber. Functional data in PMID:12645947 shows role of MRC1 in binding HIV-1, and PMID:24969847 shows association of MRC1 SNP and sustained viral response to Hepatitis-C virus.; to: Comment on list classification: Updated rating from Red to Amber. Functional data in PMID:12645947 shows role of MRC1 in binding HIV-1, and PMID:24969847 shows association of MRC1 SNP and sustained viral response to Hepatitis-C virus. Papers also demonstrate variants are associated with susceptibility to other infectious diseases including leprosy (PMID:22392581) and pulmonary tuburculosis (PMID:23653008, 22393309).
COVID-19 research v0.283 MRC1 Rebecca Foulger Publications for gene: MRC1 were set to 12645947; 24016730; 24969847
COVID-19 research v0.282 MRC1 Rebecca Foulger Classified gene: MRC1 as Amber List (moderate evidence)
COVID-19 research v0.282 MRC1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Functional data in PMID:12645947 shows role of MRC1 in binding HIV-1, and PMID:24969847 shows association of MRC1 SNP and sustained viral response to Hepatitis-C virus.
COVID-19 research v0.282 MRC1 Rebecca Foulger Gene: mrc1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.281 MRC1 Rebecca Foulger Publications for gene: MRC1 were set to 12645947; 24016730
COVID-19 research v0.280 MRC1 Rebecca Foulger commented on gene: MRC1: PMID:24969847. Peng et al., 2014 evaluated whether polymorphisms of MRC-1 and IL-28B genes are associated with the treatment outcome of patients infected with hepatitis C (HCV). Among the MRC-1 SNPs, rs691005 was found to be associated with sustained viral responses (SVR) in HCV-1-infected patients.
COVID-19 research v0.280 MRC1 Rebecca Foulger changed review comment from: HIVEP1 was identified through an OMIM search for potential viral susceptibility genes. Added to panel based on initial triage by Illumina (Tier 5 grouping) and additional curation. Notes from Julie Taylor and Alison Coffey (Illumina): One function of the receptor is to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi, so that they can be neutralized by phagocytic engulfment.
Sources: Other; to: MRC1 was identified through an OMIM search for potential viral susceptibility genes. Added to panel based on initial triage by Illumina (Tier 5 grouping) and additional curation. Notes from Julie Taylor and Alison Coffey (Illumina): One function of the receptor is to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi, so that they can be neutralized by phagocytic engulfment.
Sources: Other
COVID-19 research v0.280 MRC1 Rebecca Foulger Publications for gene: MRC1 were set to 12645947
COVID-19 research v0.279 MRC1 Rebecca Foulger Publications for gene: MRC1 were set to
COVID-19 research v0.278 MRC1 Rebecca Foulger commented on gene: MRC1: PMID:12645947. Nguyen and Hildreth (2003) showed that MRC1 (also called MMR) mediated the initial association of human immunodeficiency virus with macrophages lacking expression of DCSIGN, concluding that MRC1 (MMR) has a substantial role in binding and transmission of HIV-1 by macrophages.
COVID-19 research v0.278 MRC1 Rebecca Foulger gene: MRC1 was added
gene: MRC1 was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: MRC1 was set to Unknown
Added comment: HIVEP1 was identified through an OMIM search for potential viral susceptibility genes. Added to panel based on initial triage by Illumina (Tier 5 grouping) and additional curation. Notes from Julie Taylor and Alison Coffey (Illumina): One function of the receptor is to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi, so that they can be neutralized by phagocytic engulfment.
Sources: Other
COVID-19 research v0.277 MIF Rebecca Foulger changed review comment from: PMID:30944975. de Souza et al 2019 demonstrate in mince that MIF is expressed during RSV infection and controls the release of pro-inflammatory cytokines from macrophages in an in vitro model.; to: PMID:30944975. de Souza et al 2019 demonstrate in mice that MIF is expressed during RSV infection and controls the release of pro-inflammatory cytokines from macrophages in an in vitro model.
COVID-19 research v0.277 MIF Rebecca Foulger Classified gene: MIF as Amber List (moderate evidence)
COVID-19 research v0.277 MIF Rebecca Foulger Added comment: Comment on list classification: Upgraded rating from Red to Amber. Several animal models showing that MIF is expressed during viral infection (PMIDs:30944975, 31292300, 17909632) plus study of MIF polymorphisms and West Nile virus infection in PMID:26638028.
COVID-19 research v0.277 MIF Rebecca Foulger Gene: mif has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.276 MIF Rebecca Foulger commented on gene: MIF: PMID:31292300. Smith et al., 2019 showed that, during influenza viral infection, Mif-deficient mice have less inflammation, viral load, and mortality compared with WT control mice.
COVID-19 research v0.276 MIF Rebecca Foulger commented on gene: MIF: PMID:26638028. Das et al., 2016 examined functional polymorphisms in MIF in a cohort of 454 North American patients with neuroinvasive West Nile virus (WNV) disease and found patients homozygous for high-expression MIF allels to be >20 fold more likely to have WNV encephalitis.
COVID-19 research v0.276 MIF Rebecca Foulger commented on gene: MIF: PMID:30944975. de Souza et al 2019 demonstrate in mince that MIF is expressed during RSV infection and controls the release of pro-inflammatory cytokines from macrophages in an in vitro model.
COVID-19 research v0.276 MIF Rebecca Foulger changed review comment from: Comment on list classification: MIF was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel initially as Red. Notes from Julie Taylor and Alison Coffey (Illumina): Arjona et al. (2007) found that blocking Mif action in mice either by antibody, small molecule antagonist, or gene deletion increased resistance to West Nile Virus lethality.; to: Comment on list classification: MIF was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping), added to panel initially as Red awaiting further curation. Notes from Julie Taylor and Alison Coffey (Illumina): Arjona et al. (2007) found that blocking Mif action in mice either by antibody, small molecule antagonist, or gene deletion increased resistance to West Nile Virus lethality.
COVID-19 research v0.276 MIF Rebecca Foulger changed review comment from: Comment on list classification: MIF was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel initially as Red.; to: Comment on list classification: MIF was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel initially as Red. Notes from Julie Taylor and Alison Coffey (Illumina): Arjona et al. (2007) found that blocking Mif action in mice either by antibody, small molecule antagonist, or gene deletion increased resistance to West Nile Virus lethality.
COVID-19 research v0.276 MIF Rebecca Foulger Classified gene: MIF as Red List (low evidence)
COVID-19 research v0.276 MIF Rebecca Foulger Added comment: Comment on list classification: MIF was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel initially as Red.
COVID-19 research v0.276 MIF Rebecca Foulger Gene: mif has been classified as Red List (Low Evidence).
COVID-19 research v0.275 MIF Rebecca Foulger Phenotypes for gene: MIF were changed from to {Rheumatoid arthritis, systemic juvenile, susceptibility to}, 604302
COVID-19 research v0.274 MIF Rebecca Foulger gene: MIF was added
gene: MIF was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: MIF was set to Unknown
Publications for gene: MIF were set to 17909632
Added comment: PMID:17909632. Arjona et al. (2007) showed that patients with acute West Nile virus (WNV) infection had increased levels of MIF in plasma and cerebrospinal fluid. Studies in mice showed that MIF is involved in WNV pathogenesis.
Sources: Other
COVID-19 research v0.273 MICA Rebecca Foulger Classified gene: MICA as Amber List (moderate evidence)
COVID-19 research v0.273 MICA Rebecca Foulger Added comment: Comment on list classification: MICA was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, upgraded rating from Red to Amber: A number of publications report association between MICA variants and HBV‐related hepatocellular carcinoma. Additional papers investigate MICA polymorphisms and response to viral infections/recovery (e.g. PMIDs:28925058, 15029237).
COVID-19 research v0.273 MICA Rebecca Foulger Gene: mica has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.272 MICA Rebecca Foulger Publications for gene: MICA were set to https://doi.org/10.1101/499988; 28925058; 31033131; 15029237
COVID-19 research v0.271 MICA Rebecca Foulger Publications for gene: MICA were set to https://doi.org/10.1101/499988; 28925058; 31033131
COVID-19 research v0.270 MICA Rebecca Foulger commented on gene: MICA: PMID:15029237. Karacki et al., 2004 investigated whether MICA polymorphisms are associated with HCV recovery. They compared the frequency of all known MICA polymorphisms in 2 large cohorts of people who recovered from either HCV or HBV infection and controls. Of the 27 unique MICA polymorphisms examined, only one was detected more often in persons who had cleared HCV infection, compared with controls: MICA*015. However <4% of all those examined with viral clearance were MICA*015 positive. They cannot exclude the possibility that MICA*015 is tightly linked to another allele that is responsible for the association.
COVID-19 research v0.270 MICA Rebecca Foulger changed review comment from: Publications on association between MICA variants and hepatitis B virus (HBV) infection and HBV‐related hepatocellular carcinoma (PMIDs:31419949, 29584564).; to: Several publications on association between MICA variants and hepatitis B virus (HBV) infection and HBV‐related hepatocellular carcinoma (PMIDs:31419949, 29584564,25270965).
COVID-19 research v0.270 MICA Rebecca Foulger commented on gene: MICA: Publications on association between MICA variants and hepatitis B virus (HBV) infection and HBV‐related hepatocellular carcinoma (PMIDs:31419949, 29584564).
COVID-19 research v0.270 MICA Rebecca Foulger Phenotypes for gene: MICA were changed from to primary immunodeficiency
COVID-19 research v0.269 MICA Rebecca Foulger Publications for gene: MICA were set to
COVID-19 research v0.268 MICA Rebecca Foulger commented on gene: MICA: PMID:28925058. Luo et al., 2017 examined MICA/MIBC gene polymorphisms and respiratory syncytial virus (RSV) infection in 135 paediatric patients with and without pneuomina after RSV infection. Allele MICA*002:01/A9 and haplotype MICA*002:01-MICB*005:02 were negatively associated with RSV respiratory tract infections.
COVID-19 research v0.268 MICA Rebecca Foulger commented on gene: MICA
COVID-19 research v0.268 SLC1A5 Catherine Snow gene: SLC1A5 was added
gene: SLC1A5 was added to COVID-19 research. Sources: Expert list
Mode of inheritance for gene: SLC1A5 was set to Unknown
Review for gene: SLC1A5 was set to RED
Added comment: The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus, associated viruses are non-human
Sources: Expert list
COVID-19 research v0.267 LILRB1 Rebecca Foulger commented on gene: LILRB1: PMID:29528338. Davidson et al., 2018 tested whether LILRB1 genotype influences HCMV susceptibility by analysing LILRB1 genotypes (5 SNPs) in a group of 67 Canadian transplant patients. There was no association between LILRB1 SNPs and virus replication within the entire STCS population, but when the analyses were restricted to kidney transplant recipients, a significant association of rs10423364 was found with HCMV infection.
COVID-19 research v0.267 LILRB1 Rebecca Foulger commented on gene: LILRB1: PMID:32321755. Yu et al., 2020 studied a polymorphic 3-kb region within LILRB1 intron 1 that binds the transcription factor YY1 to regulate LILRB1 levels.
COVID-19 research v0.267 LILRB1 Rebecca Foulger commented on gene: LILRB1: PMID:30461037. Cadena-Mota et al., 2018 show that cytomegalovirus infection has a major effect on LILRB1 expression in NK and other mononuclear cells, and polymorphisms in the LILRB1 regulatory region appear to have a modulatory influence over this effect.
COVID-19 research v0.267 LILRB1 Rebecca Foulger Classified gene: LILRB1 as Amber List (moderate evidence)
COVID-19 research v0.267 LILRB1 Rebecca Foulger Added comment: Comment on list classification: HIVEP1 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel as Amber. PMID:29528338 study investigates LILRB1 genotype and viral susceptibility and finds an association within transplant patients (but not within the population as a whole).
COVID-19 research v0.267 LILRB1 Rebecca Foulger Gene: lilrb1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.266 LILRB1 Rebecca Foulger commented on gene: LILRB1
COVID-19 research v0.266 LILRB1 Rebecca Foulger gene: LILRB1 was added
gene: LILRB1 was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: LILRB1 was set to Unknown
Publications for gene: LILRB1 were set to 30461037; 32321755; 29528338
Phenotypes for gene: LILRB1 were set to HCMV susceptibility
COVID-19 research v0.265 KHDRBS1 Rebecca Foulger Classified gene: KHDRBS1 as Amber List (moderate evidence)
COVID-19 research v0.265 KHDRBS1 Rebecca Foulger Added comment: Comment on list classification: KHDRBS1 (SAM68) was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel as Amber. Functional evidence to suggest KHDRBS1 (SAM68) may serve as a proviral factor facilitate viral replication through interaction with the viral genome. A number of papers report interaction of KHDRBS1 (SAM68) and viral elements (e.g. PMIDs:26695943, 26202240, 27057671, 15701759) to positive regulate viral infection (although the viral processes affected differ between papers).
COVID-19 research v0.265 KHDRBS1 Rebecca Foulger Gene: khdrbs1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.264 KHDRBS1 Rebecca Foulger commented on gene: KHDRBS1: Notes from Julie Taylor and Alison Coffey (Illumina): KHDRBS1 belongs to the evolutionarily conserved signal transduction activator of RNA (STAR) family of RNA-binding proteins. These proteins play key roles during cell differentiation and development (summary by Bianchi et al., 2010). Cote et al. (2003, PMID:12529443) noted that KHDRBS1 (SAM68) can export unspliced human immunodeficiency virus (HIV) RNAs, and they found that treatment of cells with methylase inhibitors prevented the ability of KHDRBS1 (SAM68) to export unspliced HIV RNAs from transfected COS-7 cells.
COVID-19 research v0.264 KHDRBS1 Rebecca Foulger gene: KHDRBS1 was added
gene: KHDRBS1 was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: KHDRBS1 was set to Unknown
Publications for gene: KHDRBS1 were set to 12529443; 26695943; 26202240; 27057671; 15701759; 31068419
Added comment: PMID:31068419. Qin et al., 2019 report that KHDRBS1 (SAM68) promotes hepatitis C virus (HCV) replication without affecting viral translation. HCV infection triggers the translocation of the SAM68 protein from the nucleus to the cytoplasm, where it interacts with the HCV RNA genome.
Sources: Other
COVID-19 research v0.263 HIVEP1 Rebecca Foulger Classified gene: HIVEP1 as Red List (low evidence)
COVID-19 research v0.263 HIVEP1 Rebecca Foulger Added comment: Comment on list classification: HIVEP1 was identified through an OMIM search for potential viral susceptibility genes. Based on initial triage by Illumina (Tier 5 grouping) and additional curation, added to panel as Red. Not yet associated with an OMIM disorder. No direct evidence for a role in viral infection, but binds a DNA sequence that is common in the enhancer elements of numerous viral promoters including simian virus 40, cytomegalovirus and HIV.
COVID-19 research v0.263 HIVEP1 Rebecca Foulger Gene: hivep1 has been classified as Red List (Low Evidence).
COVID-19 research v0.262 HIVEP1 Rebecca Foulger Added comment: Comment on publications: Note that PMID:24719322 (Modulation of TLR3, TLR4 and TLR7 Mediated IFN-β, Rantes and TNFα Production by HIVEP1) was withdrawn by the author.
COVID-19 research v0.262 HIVEP1 Rebecca Foulger Publications for gene: HIVEP1 were set to
COVID-19 research v0.261 HIVEP1 Rebecca Foulger commented on gene: HIVEP1
COVID-19 research v0.261 HIVEP1 Rebecca Foulger gene: HIVEP1 was added
gene: HIVEP1 was added to COVID-19 research. Sources: Other
Mode of inheritance for gene: HIVEP1 was set to Unknown
COVID-19 research v0.260 CXorf36 Sarah Leigh Tag new-gene-name tag was added to gene: CXorf36.
COVID-19 research v0.260 ZNF34 Sarah Leigh reviewed gene: ZNF34: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 ZFP36 Sarah Leigh reviewed gene: ZFP36: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 ZC3HC1 Sarah Leigh reviewed gene: ZC3HC1: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 TUBGCP3 Sarah Leigh reviewed gene: TUBGCP3: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 TSPAN14 Sarah Leigh reviewed gene: TSPAN14: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 TNIP1 Sarah Leigh reviewed gene: TNIP1: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 SLC13A4 Sarah Leigh reviewed gene: SLC13A4: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 ODC1 Sarah Leigh reviewed gene: ODC1: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 MTPAP Sarah Leigh reviewed gene: MTPAP: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 MICA Sarah Leigh reviewed gene: MICA: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 MED13L Sarah Leigh reviewed gene: MED13L: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 IVNS1ABP Sarah Leigh reviewed gene: IVNS1ABP: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 FOXM1 Sarah Leigh reviewed gene: FOXM1: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 FBRS Sarah Leigh reviewed gene: FBRS: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 CXorf36 Sarah Leigh reviewed gene: CXorf36: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.260 ABI3 Sarah Leigh reviewed gene: ABI3: Rating: RED; Mode of pathogenicity: ; Publications: https://doi.org/10.1101/499988; Phenotypes: primary immunodeficiency; Mode of inheritance: Unknown
COVID-19 research v0.259 ZNF34 Sarah Leigh gene: ZNF34 was added
gene: ZNF34 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ZNF34 was set to Unknown
COVID-19 research v0.258 ZFP36 Sarah Leigh gene: ZFP36 was added
gene: ZFP36 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ZFP36 was set to Unknown
COVID-19 research v0.257 ZC3HC1 Sarah Leigh gene: ZC3HC1 was added
gene: ZC3HC1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ZC3HC1 was set to Unknown
COVID-19 research v0.256 TUBGCP3 Sarah Leigh gene: TUBGCP3 was added
gene: TUBGCP3 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: TUBGCP3 was set to Unknown
COVID-19 research v0.255 TSPAN14 Sarah Leigh gene: TSPAN14 was added
gene: TSPAN14 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: TSPAN14 was set to Unknown
COVID-19 research v0.254 TNIP1 Sarah Leigh gene: TNIP1 was added
gene: TNIP1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: TNIP1 was set to Unknown
COVID-19 research v0.253 SLC13A4 Sarah Leigh gene: SLC13A4 was added
gene: SLC13A4 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SLC13A4 was set to Unknown
COVID-19 research v0.252 ODC1 Sarah Leigh gene: ODC1 was added
gene: ODC1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ODC1 was set to Unknown
COVID-19 research v0.251 MTPAP Sarah Leigh gene: MTPAP was added
gene: MTPAP was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MTPAP was set to Unknown
COVID-19 research v0.250 MICA Sarah Leigh gene: MICA was added
gene: MICA was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MICA was set to Unknown
COVID-19 research v0.249 MED13L Sarah Leigh gene: MED13L was added
gene: MED13L was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: MED13L was set to Unknown
COVID-19 research v0.248 IVNS1ABP Sarah Leigh gene: IVNS1ABP was added
gene: IVNS1ABP was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: IVNS1ABP was set to Unknown
COVID-19 research v0.247 FOXM1 Sarah Leigh gene: FOXM1 was added
gene: FOXM1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: FOXM1 was set to Unknown
COVID-19 research v0.246 FBRS Sarah Leigh gene: FBRS was added
gene: FBRS was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: FBRS was set to Unknown
COVID-19 research v0.245 CXorf36 Sarah Leigh gene: CXorf36 was added
gene: CXorf36 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: CXorf36 was set to Unknown
COVID-19 research v0.244 ABI3 Sarah Leigh gene: ABI3 was added
gene: ABI3 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: ABI3 was set to Unknown
COVID-19 research v0.243 SOCS1 Sarah Leigh edited their review of gene: SOCS1: Changed publications: 12588885, 12588885, 18172216, https://doi.org/10.1101/499988
COVID-19 research v0.243 SOCS1 Sarah Leigh changed review comment from: PMID 12588885: In coxsackievirus-infected mice cardiac myocyte-specific transgenic expression of SOCS1 inhibited virus-induced signaling of JAK and STAT resulting in increased viral replication, cardiomyopathy, and mortality compared to controls. Inhibition of SOCS in cardiac myocytes increased myocyte resistance to the acute cardiac injury of enteroviral infection. It was suggested that inhibition of SOCS could augment the host-cell antiviral system and might prevent viral-mediated end-organ damage during the early stages of infection.
Sources: Literature; to: PMID 12588885: In coxsackievirus-infected mice cardiac myocyte-specific transgenic expression of SOCS1 inhibited virus-induced signaling of JAK and STAT resulting in increased viral replication, cardiomyopathy, and mortality compared to controls. Inhibition of SOCS in cardiac myocytes increased myocyte resistance to the acute cardiac injury of enteroviral infection. It was suggested that inhibition of SOCS could augment the host-cell antiviral system and might prevent viral-mediated end-organ damage during the early stages of infection.
https://doi.org/10.1101/499988 reports: Genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci).

Sources: Literature
COVID-19 research v0.243 SOCS1 Sarah Leigh gene: SOCS1 was added
gene: SOCS1 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: SOCS1 was set to Unknown
Publications for gene: SOCS1 were set to 12588885; 12588885; 18172216
Phenotypes for gene: SOCS1 were set to primary immunodeficiency
Review for gene: SOCS1 was set to AMBER
Added comment: PMID 12588885: In coxsackievirus-infected mice cardiac myocyte-specific transgenic expression of SOCS1 inhibited virus-induced signaling of JAK and STAT resulting in increased viral replication, cardiomyopathy, and mortality compared to controls. Inhibition of SOCS in cardiac myocytes increased myocyte resistance to the acute cardiac injury of enteroviral infection. It was suggested that inhibition of SOCS could augment the host-cell antiviral system and might prevent viral-mediated end-organ damage during the early stages of infection.
Sources: Literature
COVID-19 research v0.242 PTPN2 Sarah Leigh gene: PTPN2 was added
gene: PTPN2 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: PTPN2 was set to Unknown
Publications for gene: PTPN2 were set to 19825843; https://doi.org/10.1101/499988
Phenotypes for gene: PTPN2 were set to primary immunodeficiency
Review for gene: PTPN2 was set to RED
Added comment: https://doi.org/10.1101/499988 reports: genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci).
Sources: Literature
COVID-19 research v0.241 CASP3 Catherine Snow Classified gene: CASP3 as Green List (high evidence)
COVID-19 research v0.241 CASP3 Catherine Snow Gene: casp3 has been classified as Green List (High Evidence).
COVID-19 research v0.240 CASP3 Catherine Snow gene: CASP3 was added
gene: CASP3 was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: CASP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CASP3 were set to 32200494; 24903211; 21160486; 23894522
Phenotypes for gene: CASP3 were set to Kawasaki disease
Added comment: Number of SNPs identified in CASP3 associated with risk of Kawaski Disease. Summarised in PMID:32200494
Sources: Literature
COVID-19 research v0.239 BLK Catherine Snow changed review comment from: Number of SNPs identified in BLK associated with risk of Kawaski Disease
Sources: Literature; to: Number of SNPs identified in BLK associated with risk of Kawaski Disease. Summarised in PMID:32200494
Sources: Literature
COVID-19 research v0.239 BLK Catherine Snow Publications for gene: BLK were set to 22446961; 26182267; 24023612; 25645453
COVID-19 research v0.238 BLK Catherine Snow Classified gene: BLK as Green List (high evidence)
COVID-19 research v0.238 BLK Catherine Snow Gene: blk has been classified as Green List (High Evidence).
COVID-19 research v0.237 BLK Catherine Snow gene: BLK was added
gene: BLK was added to COVID-19 research. Sources: Literature
Mode of inheritance for gene: BLK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BLK were set to 22446961; 26182267; 24023612; 25645453
Phenotypes for gene: BLK were set to Kawasaki disease
Review for gene: BLK was set to GREEN
Added comment: Number of SNPs identified in BLK associated with risk of Kawaski Disease
Sources: Literature
COVID-19 research v0.235 Eleanor Williams Panel name changed from Viral susceptibility to COVID-19 research
List of related panels changed from to Viral susceptibility
COVID-19 research v0.234 ANPEP Eleanor Williams gene: ANPEP was added
gene: ANPEP was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: ANPEP was set to Unknown
Publications for gene: ANPEP were set to 28643204
Added comment: PMID: 28643204 - de Wilde et al 2018 - in a review of known coronavirus entry receptors APN/ANPEP is listed as a entry receptor for several Alphacoronaviruses (Table 1). Sars-cov-2 is a Betacoronavirus.
Sources: Literature
COVID-19 research v0.233 DPP4 Eleanor Williams Publications for gene: DPP4 were set to 23486063; 24554656; 24599590; 25589660; 26124093; https://doi.org/10.1101/2020.04.30.071274
COVID-19 research v0.232 DPP4 Eleanor Williams commented on gene: DPP4: PMID: 31883094 - Leist et al 2020 - describe the generation of the 288-330+/+ MERS-CoV mouse model in which mice were made susceptible to MERS-CoV by modifying two amino acids on mDPP4 (A288 and T330).
COVID-19 research v0.232 DPP4 Eleanor Williams commented on gene: DPP4
COVID-19 research v0.232 ACE2 Eleanor Williams changed review comment from: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations.; to: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations. East Asian populations have much higher AFs in the eQTL variants associated with higher ACE2 expression in tissues.
COVID-19 research v0.232 ACE2 Eleanor Williams Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651; 32015507
COVID-19 research v0.231 ACE2 Eleanor Williams commented on gene: ACE2: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations.
COVID-19 research v0.231 HSPA5 Eleanor Williams gene: HSPA5 was added
gene: HSPA5 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: HSPA5 was set to Unknown
Publications for gene: HSPA5 were set to 3216948
Review for gene: HSPA5 was set to RED
Added comment: PMID:3216948 - Ibrahim et al 2020 - predict that HSPA5 (GRP78) might bind with COVID-19 spike
Sources: Literature
COVID-19 research v0.230 ACE2 Eleanor Williams commented on gene: ACE2: PMID: 32249956 Hussain et al 2020 - show through molecular modelling that ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein of SARS-CoV-2
COVID-19 research v0.230 TMPRSS2 Eleanor Williams Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843; 25904605; 24600012; 24522916; 32327758
COVID-19 research v0.229 TMPRSS2 Eleanor Williams Deleted their review
COVID-19 research v0.229 TMPRSS2 Eleanor Williams Deleted their comment
COVID-19 research v0.229 ITPKC Catherine Snow Publications for gene: ITPKC were set to 18084290; 20045869
COVID-19 research v0.228 ITPKC Catherine Snow Classified gene: ITPKC as Green List (high evidence)
COVID-19 research v0.228 ITPKC Catherine Snow Gene: itpkc has been classified as Green List (High Evidence).
COVID-19 research v0.227 FCGR2A Catherine Snow edited their review of gene: FCGR2A: Added comment: Has been identified as a risk loci for Kawasaki disease.; Changed publications: 19494086, 12752683, 16185324, 22446962
COVID-19 research v0.227 ORAI1 Catherine Snow reviewed gene: ORAI1: Rating: ; Mode of pathogenicity: None; Publications: 30853710, 26789410; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.227 TMPRSS2 Eleanor Williams Added comment: Comment on publications: Adding pubmed:32327758 - using single cell RNA-sequencing they confirmed the expression of ACE2 in multiple tissues shown in previous studies with added information on tissues not previously investigated, including nasal epithelium and cornea and its co-expression with TMPRSS2
COVID-19 research v0.227 TMPRSS2 Eleanor Williams Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843; 25904605; 24600012; 24522916
COVID-19 research v0.226 SCN5A Eleanor Williams changed review comment from: PMID: 32380288 Giudicessi et al 2020 - discuss the potential of p.Ser1103Tyr-SCN5A to exacerbate outcome-related health disparities in the COVID-19 pandemic.; to: PMID: 32380288 Giudicessi et al 2020 - discuss the potential of p.Ser1103Tyr-SCN5A to exacerbate outcome-related health disparities in the COVID-19 pandemic.

Keeping red for now, as this paper is speculation - no real data.
COVID-19 research v0.226 SCN5A Eleanor Williams Publications for gene: SCN5A were set to
COVID-19 research v0.225 SCN5A Eleanor Williams reviewed gene: SCN5A: Rating: ; Mode of pathogenicity: None; Publications: 32380288; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.225 APOE Eleanor Williams Classified gene: APOE as Amber List (moderate evidence)
COVID-19 research v0.225 APOE Eleanor Williams Added comment: Comment on list classification: Rating amber as one study reported showing that a variant (ApoE e4 allele) is associated with hospitalization with COVID-19.
COVID-19 research v0.225 APOE Eleanor Williams Gene: apoe has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.224 APOE Eleanor Williams gene: APOE was added
gene: APOE was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: APOE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOE were set to https://doi.org/10.1101/2020.05.07.20094409
Phenotypes for gene: APOE were set to dementia
Added comment: Preprint: https://doi.org/10.1101/2020.05.07.20094409 Kuo et al 2020 - Using UK biobank data they found that the ApoE e4 allele ( rs429358) increases risks of being hospitalized with COVID-19, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes.
ApoE e4 allele frequency is higher in people of African ancestry than in Europeans, and
preliminary results suggest that ApoE e4 prevalence makes a modest contribution to the
excess incidence of COVID-19 in Blacks.
Sources: Literature
COVID-19 research v0.223 DDX58 Sarah Leigh Classified gene: DDX58 as Amber List (moderate evidence)
COVID-19 research v0.223 DDX58 Sarah Leigh Added comment: Comment on list classification: Wild type DDX58 confers detection and eradication of replicating viral genomes, variants in this gene could therefore interfere with this mechanism.
COVID-19 research v0.223 DDX58 Sarah Leigh Gene: ddx58 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.222 DDX58 Sarah Leigh Publications for gene: DDX58 were set to 21939710; 16625202
COVID-19 research v0.221 DDX58 Sarah Leigh gene: DDX58 was added
gene: DDX58 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: DDX58 was set to Unknown
Publications for gene: DDX58 were set to 21939710; 16625202
Added comment: PMID 21939710 found DDX5 (formerly known as RIGI) was essential for virus-induced expression of IRF3 and concluded that DDX5 is essential for detection and eradication of replicating viral genomes. PMID 16625202 reported that DDX58 is essential for the production of interferons in response to certain RNA viruses including paramyxoviruses, influenza virus, and Japanese encephalitis virus.
Sources: Literature
COVID-19 research v0.220 DPP4 Sarah Leigh Publications for gene: DPP4 were set to 23486063; 24554656; 24599590; 25589660; 26124093
COVID-19 research v0.219 DPP4 Sarah Leigh Classified gene: DPP4 as Amber List (moderate evidence)
COVID-19 research v0.219 DPP4 Sarah Leigh Gene: dpp4 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.218 DPP4 Sarah Leigh gene: DPP4 was added
gene: DPP4 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: DPP4 was set to Unknown
Publications for gene: DPP4 were set to 23486063; 24554656; 24599590; 25589660; 26124093
Review for gene: DPP4 was set to AMBER
Added comment: DPP4 is a functional receptor for human coronavirus-Erasmus Medical Center (hCoV-EMC), also known as Middle East respiratory syndrome coronavirus (MERS-CoV). Blades 4 and 5 of the 8-blade beta-propeller region of DPP4 confer binding and susceptibility to MERS-CoV (PMID 24554656). Rhodants are not susceptible to MERS-CoV, however, a mouse models expressing human DPP4 became infected with MERS-CoV (PMID 24599590; 25589660; 26124093).
Sources: Literature
COVID-19 research v0.217 MX1 Sarah Leigh gene: MX1 was added
gene: MX1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: MX1 was set to Unknown
Publications for gene: MX1 were set to 3162334; 14872030; 21935451; https://doi.org/10.1101/2020.05.04.075911
Review for gene: MX1 was set to AMBER
Added comment: MX1 is an interferon-induced protein with antiviral activity (PMID 3162334).
PMID 14872030 c.-88G>T was more frequent in 40 unrelated Japanese patients with subacute sclerosing panencephalitisis (associated with CNS infection with measles virus), than in 90 controls (0.42 in patients vs 0.29 in controls). Variant c.-88G>T results increased MX1 expression, the authors suggest that MX1 may paradoxically enable persistence of the virus in the CNS by attenuating viral gene expression and preventing complete immunologic clearance.
PMID 21935451 concluded that genetic variation in the interferon response pathway is associated with risk for symptomatic West Nile viru infection and disease progression.
Preprint https://doi.org/10.1101/2020.05.04.075911 Reports that rs35074065 of TMPRSS2 results in increased expression of the nearby gene MX1.
Sources: Literature
COVID-19 research v0.216 BST2 Rebecca Foulger Classified gene: BST2 as Red List (low evidence)
COVID-19 research v0.216 BST2 Rebecca Foulger Added comment: Comment on list classification: Added to panel as a Red gene: present in latest release of UniProt COVID portal. Plays a role in tethering viruses to the host cell to block viral release. Recent research (PMID:31199522) shows interaction with SARS-CoV spike protein, which inhibits BST2 function and allows viral release.
COVID-19 research v0.216 BST2 Rebecca Foulger Gene: bst2 has been classified as Red List (Low Evidence).
COVID-19 research v0.215 BST2 Rebecca Foulger commented on gene: BST2: PMID:31199522. Wang et al., 2019 show that SARS-CoV spike (S) glycoprotein antagonises the BST2 tethering of SARS-CoV via BST2 downregulation. The authors show colocalization BST2 and SARS-CoV S protein.
COVID-19 research v0.215 BST2 Rebecca Foulger gene: BST2 was added
gene: BST2 was added to Viral susceptibility. Sources: Literature,Other
Mode of inheritance for gene: BST2 was set to Unknown
Publications for gene: BST2 were set to 31199522
Added comment: BST2 is present in the UniProt COVID portal (11th May 2020 Release): https://covid-19.uniprot.org/uniprotkb/Q10589. BST2 is an IFN-induced antiviral host restriction factor which physically blocks the release of viruses by directly tethering nascent virions to the membranes of infected cells.
Sources: Literature, Other
COVID-19 research v0.214 TMPRSS2 Sarah Leigh changed review comment from: Preprint https://doi.org/10.1101/2020.05.04.075911 reports rs35074065 of TMPRSS2 results in the overexpression of both TMPRSS2 and a nearby gene MX1. rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.; to: Preprint https://doi.org/10.1101/2020.05.04.075911 reports rs35074065 of TMPRSS2 results in the overexpression of both TMPRSS2 and a nearby gene MX1. rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele of rs35074065, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G variant viral Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.
COVID-19 research v0.214 KPNA2 Rebecca Foulger Classified gene: KPNA2 as Red List (low evidence)
COVID-19 research v0.214 KPNA2 Rebecca Foulger Added comment: Comment on list classification: Added KPNA2 to the panel as a Red gene. Present in the latest UniProt COVID portal release based on functional data that show an interaction with SARS-COVID viral ORF6 protein.
COVID-19 research v0.214 KPNA2 Rebecca Foulger Gene: kpna2 has been classified as Red List (Low Evidence).
COVID-19 research v0.213 KPNA2 Rebecca Foulger changed review comment from: KPNA2 present in the UniProt COVID portal (11th May 2020 Release): https://covid-19.uniprot.org/uniprotkb/P52292. KPNA2 acts as a nuclear import factor. KPNA2 is retained in ER/Golgi membranes upon interaction with SARS-COV virus ORF6 protein, and therefore KPNA2 is unable to transport STAT1 into the nucleus, therby blocking the expression of STAT1-activated genes that establish an antiviral state (PMID:17596301).
Sources: Literature, Other; to: KPNA2 is present in the UniProt COVID portal (11th May 2020 Release): https://covid-19.uniprot.org/uniprotkb/P52292. KPNA2 acts as a nuclear import factor. KPNA2 is retained in ER/Golgi membranes upon interaction with SARS-COV virus ORF6 protein, and therefore KPNA2 is unable to transport STAT1 into the nucleus, therby blocking the expression of STAT1-activated genes that establish an antiviral state (PMID:17596301).
Sources: Literature, Other
COVID-19 research v0.213 KPNA2 Rebecca Foulger gene: KPNA2 was added
gene: KPNA2 was added to Viral susceptibility. Sources: Literature,Other
Mode of inheritance for gene: KPNA2 was set to Unknown
Publications for gene: KPNA2 were set to 17596301
Added comment: KPNA2 present in the UniProt COVID portal (11th May 2020 Release): https://covid-19.uniprot.org/uniprotkb/P52292. KPNA2 acts as a nuclear import factor. KPNA2 is retained in ER/Golgi membranes upon interaction with SARS-COV virus ORF6 protein, and therefore KPNA2 is unable to transport STAT1 into the nucleus, therby blocking the expression of STAT1-activated genes that establish an antiviral state (PMID:17596301).
Sources: Literature, Other
COVID-19 research v0.212 SH3BP2 Catherine Snow Classified gene: SH3BP2 as Red List (low evidence)
COVID-19 research v0.212 SH3BP2 Catherine Snow Added comment: Comment on list classification: Demoting gene based on expert review
COVID-19 research v0.212 SH3BP2 Catherine Snow Gene: sh3bp2 has been classified as Red List (Low Evidence).
COVID-19 research v0.211 FURIN Rebecca Foulger Publications for gene: FURIN were set to
COVID-19 research v0.210 FURIN Rebecca Foulger Classified gene: FURIN as Amber List (moderate evidence)
COVID-19 research v0.210 FURIN Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber: Although no SNP studies, or potential variants identified yet, recent papers (e.g. PMID:32362314) and preprints have identified a role for Furin protease activity in SARS-CoV-2 entry into human cells. Therefore changes to Furin sequence could potentially alter viral susceptibility.
COVID-19 research v0.210 FURIN Rebecca Foulger Gene: furin has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.209 FURIN Rebecca Foulger commented on gene: FURIN: PMID:32362314. Hoffmann et al., 2020 report that Furin cleaves the SARS-CoV-2 spike protein at the S1/S2 site, and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Therefore furin may be a potential target for therapuetic intervention.
COVID-19 research v0.209 FURIN Rebecca Foulger commented on gene: FURIN: PMID:25974265. Hardes et al., 2015. Furing is required for H7N1 and H5N1 influenza virus infection, probably by cleaving hemagglutinin. Therefore inhibition of Furin is a potential strategy for short-term treatment of acute infectious diseases, including avian influenza.
COVID-19 research v0.209 FURIN Rebecca Foulger commented on gene: FURIN
COVID-19 research v0.209 CD14 Catherine Snow Classified gene: CD14 as Green List (high evidence)
COVID-19 research v0.209 CD14 Catherine Snow Added comment: Comment on list classification: Upgrade to Green based on expert review from Sophie Hambleton
COVID-19 research v0.209 CD14 Catherine Snow Gene: cd14 has been classified as Green List (High Evidence).
COVID-19 research v0.208 ABO Catherine Snow Classified gene: ABO as Green List (high evidence)
COVID-19 research v0.208 ABO Catherine Snow Added comment: Comment on list classification: Upgrade to Green based on expert review
COVID-19 research v0.208 ABO Catherine Snow Gene: abo has been classified as Green List (High Evidence).
COVID-19 research v0.207 SELPLG Sarah Leigh commented on gene: SELPLG: PMID: 30833724 identifies SELPLG (refered to as PSGL1 in the literature) as an HIV restriction factor, SELPLG is induced by interferon-γ in activated CD4+ T cells to inhibit HIV-1 reverse transcription and potently block viral infectivity by incorporating in progeny virions.
Preprint https://doi.org/10.1101/2020.05.01.073387 report that virion incorporation of SELPLG on SARS-CoV and SARS-CoV-2 pseudovirions blocks S protein-mediated virus attachment and infection of target cells, Suggesting that SELPLG-imprinted non-infectious viral particles could serve as a live attenuated vaccine for SARS-CoV-2 infection.
COVID-19 research v0.207 SELPLG Sarah Leigh gene: SELPLG was added
gene: SELPLG was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: SELPLG was set to Unknown
Publications for gene: SELPLG were set to 19543284; 30833724; doi.org/10.1101/2020.05.01.073387
Review for gene: SELPLG was set to RED
Added comment: In PMID 19543284 SELPLG (refered to as PSGL1 in the literature) is a receptor for 5 of 8 the Enterovirus-71 (EV71) strains. EV71 interaction and viral replication could be inhibited by monoclonal antibodies to SELPLG. The authors concluded that SELPLG-positive leukocytes are involved in the cell tropism and pathogenesis of hand, foot and mouth disease and other EV71-mediated diseases.
Sources: Literature
COVID-19 research v0.206 ACE2 Sarah Leigh changed review comment from: In preprint https://doi.org/10.1101/2020.04.30.20081257 reports increased expression of ACE2 and natriuretic peptides during heart failure, which predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection. The authors speculated that modulation levels of ACE2 and natriuretic peptides may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.; to: Preprint: https://doi.org/10.1101/2020.04.30.20081257 reports increased expression of ACE2 and natriuretic peptides during heart failure, which predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection. The authors speculated that modulation levels of ACE2 and natriuretic peptides may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.

Preprint: https://doi.org/10.1101/2020.05.03.074781 uses mCSM-PPI212 mutation effect predictor for protein-protein complex affinity, primarily validated against published experimental ACE2 variant SARS-CoV S-protein affinities to analysis variants from gnomAD. p.Gly326Glu, predicted to enhances ACE2 binding affinity for SARS-CoV-2 S, therefore a potential risk factor for COVID-19. p.Glu37Lys, p.Gly352Val and p.Asp355Asn predicted to reduce ACE2 affinity for SARS-CoV-2 S, therefore potentially protective against COVID-19.
COVID-19 research v0.206 CCL5 Sarah Leigh Classified gene: CCL5 as Green List (high evidence)
COVID-19 research v0.206 CCL5 Sarah Leigh Added comment: Comment on list classification: Based on expert review by Sophie Hambleton (Newcastle University)
COVID-19 research v0.206 CCL5 Sarah Leigh Gene: ccl5 has been classified as Green List (High Evidence).
COVID-19 research v0.205 ACE2 Sarah Leigh changed review comment from: In preprint https://doi.org/10.1101/2020.04.30.20081257 reports increased expression of ACE2 and natriuretic peptides during heart failure, which predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.; to: In preprint https://doi.org/10.1101/2020.04.30.20081257 reports increased expression of ACE2 and natriuretic peptides during heart failure, which predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection. The authors speculated that modulation levels of ACE2 and natriuretic peptides may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.
COVID-19 research v0.205 ACE2 Sarah Leigh commented on gene: ACE2
COVID-19 research v0.205 CCL5 Sarah Leigh reviewed gene: CCL5: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.02.20084673; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.205 CCR5 Sarah Leigh edited their review of gene: CCR5: Added comment: Preprint https://doi.org/10.1101/2020.05.02.20084673 reports 10 terminally-ill, critical COVID-19 patients with profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Treatment with CCR5 blocking antibody leronlimab, results in complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. From single-cell RNA-sequencing, this effect appears to be a result of reduced transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes.; Changed publications: https://doi.org/10.1101/2020.05.02.20084673
COVID-19 research v0.205 IL6 Sarah Leigh Classified gene: IL6 as Green List (high evidence)
COVID-19 research v0.205 IL6 Sarah Leigh Gene: il6 has been classified as Green List (High Evidence).
COVID-19 research v0.204 IL6 Sarah Leigh edited their review of gene: IL6: Added comment: Preprint https://doi.org/10.1101/2020.05.02.20084673 reports 10 terminally-ill, critical COVID-19 patients with profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Treatment with CCR5 blocking antibody leronlimab, results in complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. From single-cell RNA-sequencing, this effect appears to be a result of reduced transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes.; Changed publications: https://doi.org/10.1101/2020.05.02.20084673
COVID-19 research v0.204 TMPRSS2 Sarah Leigh reviewed gene: TMPRSS2: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.04.075911; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 ACE2 Rebecca Foulger commented on gene: ACE2: Added 'treatable' tag based on preprint http://biorxiv.org/cgi/content/short/2020.05.07.082230 which suggests that a modified ACE2 peptide could act as a treatment to block the viral receptor forming a complex with ACE2.
COVID-19 research v0.204 ACE2 Rebecca Foulger Tag treatable tag was added to gene: ACE2.
COVID-19 research v0.204 SNORA31 Abdelazeem Elhabyan reviewed gene: SNORA31: Rating: ; Mode of pathogenicity: None; Publications: 31806906; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 TICAM1 Abdelazeem Elhabyan reviewed gene: TICAM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22105173,26513235; Phenotypes: Herpes simplex encephalitis predisposition; Mode of inheritance: Other
COVID-19 research v0.204 ITGAM Sophie Hambleton edited their review of gene: ITGAM: Changed rating: AMBER
COVID-19 research v0.204 IL18 Sophie Hambleton edited their review of gene: IL18: Added comment: IL-18 is important in the pathogenesis of HLH (PMID:29326099) and the newly described autoinflammatory state IL18PAP-MAS (PMID: 31874111). Elevated IL-18 levels were detected in patients with COVID although not differentiating severe from mild/moderate disease (MedRxiv preprint https://doi.org/10.1101/2020.03.02.20029975). It is plausible that genetically determined differences in the activity of IL-18 might influence risk of severe COVID-19; Changed rating: AMBER
COVID-19 research v0.204 IL6 Sophie Hambleton reviewed gene: IL6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 IFNL3 Sophie Hambleton reviewed gene: IFNL3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 CD14 Sophie Hambleton reviewed gene: CD14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 CCL5 Sophie Hambleton reviewed gene: CCL5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 ABO Sophie Hambleton reviewed gene: ABO: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.204 HAVCR2 Sarah Leigh Classified gene: HAVCR2 as Green List (high evidence)
COVID-19 research v0.204 HAVCR2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in at least 20 families. PMID 30374066 haplotype analysis identified at least 12 distinct chromosome backgrounds within 7 families homozygous for rs184868814, suggestive of recurrant occurrence.
COVID-19 research v0.204 HAVCR2 Sarah Leigh Gene: havcr2 has been classified as Green List (High Evidence).
COVID-19 research v0.203 ICOSLG Sarah Leigh edited their review of gene: ICOSLG: Changed rating: RED
COVID-19 research v0.203 ICOSLG Sarah Leigh reviewed gene: ICOSLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 30498080, 31532372; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 ZNF341 Sophie Hambleton reviewed gene: ZNF341: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: immunodeficiency, recurrent infections, eczema, skeletal abnormalities, hyper-IgE, mucocutaneous candidiasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 XRCC2 Sophie Hambleton reviewed gene: XRCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 WRAP53 Sophie Hambleton reviewed gene: WRAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 UBE2T Sophie Hambleton reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 TRIM22 Sophie Hambleton reviewed gene: TRIM22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: very early onset inflammatory bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 IFITM3 Sophie Hambleton reviewed gene: IFITM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 PIK3CG Sophie Hambleton reviewed gene: PIK3CG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 TP53 Sophie Hambleton reviewed gene: TP53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.203 CDC42 Sophie Hambleton reviewed gene: CDC42: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophagocytic lymphohistiocytosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.203 TOP2B Sophie Hambleton reviewed gene: TOP2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31409799; Phenotypes: hypogammglobulinaemia, B cell deficiency, Hoffman syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.203 TNFSF11 Sophie Hambleton reviewed gene: TNFSF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 17632511; Phenotypes: osteopetrosis, osteoclast-poor; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 TNFRSF9 Sophie Hambleton reviewed gene: TNFRSF9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: immunodeficiency, autoimmunity, lymphoma, EBV predisposition; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 TMPRSS2 Sophie Hambleton reviewed gene: TMPRSS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.203 TGFBR2 Sophie Hambleton reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15731757, 16928994, 24577266; Phenotypes: Loeys Dietz syndrome, arterial aneurysms, atopy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.203 TGFBR1 Sophie Hambleton reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15731757, 16928994, 24577266; Phenotypes: Loeys Dietz syndrome, arterial aneurysms, atopy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.203 TGFB1 Sophie Hambleton reviewed gene: TGFB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: infantile-onset inflammatory bowel disease, epilepsy, brain atrophy, posterior leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 TFRC Sophie Hambleton reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642240; Phenotypes: combined immunodeficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 TCIRG1 Sophie Hambleton reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10888887; Phenotypes: infantile osteopetrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.203 IL2RB Sarah Leigh Classified gene: IL2RB as Green List (high evidence)
COVID-19 research v0.203 IL2RB Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 4 variants reported in at least 5 unrelated families (two families with the same variant had shared ethnic heritage PMID 31040185).
COVID-19 research v0.203 IL2RB Sarah Leigh Gene: il2rb has been classified as Green List (High Evidence).
COVID-19 research v0.202 STN1 Sophie Hambleton reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27432940; Phenotypes: syndromic bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.202 SRP72 Sophie Hambleton reviewed gene: SRP72: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541560; Phenotypes: aplastic anaemia, myelodysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.202 IL6R Sarah Leigh Classified gene: IL6R as Green List (high evidence)
COVID-19 research v0.202 IL6R Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 4 variants reported in at least 3 unrelated cases, together with supportive functional studies.
COVID-19 research v0.202 IL6R Sarah Leigh Gene: il6r has been classified as Green List (High Evidence).
COVID-19 research v0.201 SRP54 Sophie Hambleton reviewed gene: SRP54: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: severe congenital neutropenia, Shwachman-Diamond syndrome, exocrine pancreatic insufficiency, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.201 SNX10 Sophie Hambleton reviewed gene: SNX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499339, 23280965, 28592808; Phenotypes: infantile osteopetrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.201 SNORA31 Sophie Hambleton reviewed gene: SNORA31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: herpes simplex encephalitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.201 IFNL3 Catherine Snow Classified gene: IFNL3 as Amber List (moderate evidence)
COVID-19 research v0.201 IFNL3 Catherine Snow Gene: ifnl3 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.200 IFNL3 Catherine Snow gene: IFNL3 was added
gene: IFNL3 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: IFNL3 was set to Unknown
Review for gene: IFNL3 was set to AMBER
Added comment: IFNL3 was identified in preprint https://doi.org/10.1101/2020.04.26.20080408 "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression.
Sources: Literature
COVID-19 research v0.199 IFNL4 Catherine Snow changed review comment from: IFNL4 was identified in preprint "A gene locus that controls expression of ACE2 in virus infection"
A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression.
PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation.
Sources: Literature; to: IFNL4 was identified in preprint https://doi.org/10.1101/2020.04.26.20080408 "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression.

PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation.
Sources: Literature
COVID-19 research v0.199 IFNL4 Catherine Snow gene: IFNL4 was added
gene: IFNL4 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: IFNL4 was set to Unknown
Publications for gene: IFNL4 were set to 31776283
Review for gene: IFNL4 was set to AMBER
Added comment: IFNL4 was identified in preprint "A gene locus that controls expression of ACE2 in virus infection"
A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression.
PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation.
Sources: Literature
COVID-19 research v0.198 ITPKC Catherine Snow changed review comment from: Adding ITPKC as Kawasaki disease in children linked to coronavirus.

Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research; to: Adding ITPKC as a Kawasaki like disease in children linked to coronavirus.

Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research
COVID-19 research v0.198 ITPKC Catherine Snow changed review comment from: Adding ITPKC as Kawasaki disease in children linked to coronavirus as becoming more "common".

Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research; to: Adding ITPKC as Kawasaki disease in children linked to coronavirus.

Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research
COVID-19 research v0.198 ITPKC Catherine Snow changed review comment from: Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research; to: Adding ITPKC as Kawasaki disease in children linked to coronavirus as becoming more "common".

Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research
COVID-19 research v0.198 ITPKC Catherine Snow Classified gene: ITPKC as Amber List (moderate evidence)
COVID-19 research v0.198 ITPKC Catherine Snow Gene: itpkc has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.198 ITPKC Catherine Snow Classified gene: ITPKC as Amber List (moderate evidence)
COVID-19 research v0.198 ITPKC Catherine Snow Gene: itpkc has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.197 ITPKC Catherine Snow gene: ITPKC was added
gene: ITPKC was added to Viral susceptibility. Sources: Literature,Research
Mode of inheritance for gene: ITPKC was set to Unknown
Publications for gene: ITPKC were set to 18084290; 20045869
Phenotypes for gene: ITPKC were set to Kawasaki disease, susceptibility to, 611775
Review for gene: ITPKC was set to AMBER
Added comment: Onouchi et al (PMID:18084290) identified a functional SNP in intron 1 of ITPKC (rs28493229) that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. But Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children.
Sources: Literature, Research
COVID-19 research v0.196 IL6ST Sarah Leigh Publications for gene: IL6ST were set to 31235509; 32086639; 30309848; 28747427; 32048120
COVID-19 research v0.195 CD4 Ivone Leong Classified gene: CD4 as Amber List (moderate evidence)
COVID-19 research v0.195 CD4 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber based on expert review.

"Single individual reported, functional data, emerging gene.
Zornitza Stark (Australian Genomics), 1 May 2020" - review copied from Primary immunodeficiency (Version 2.155).
COVID-19 research v0.195 CD4 Ivone Leong Gene: cd4 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.194 CD4 Ivone Leong Phenotypes for gene: CD4 were changed from Selective CD4 cell deficiency to Selective CD4 cell deficiency; OKT4 epitope deficiency, 613949; Absence of CD4+ T cells; exuberant, relapsing, treatment-refractory warts
COVID-19 research v0.193 CD4 Ivone Leong Publications for gene: CD4 were set to 25611551
COVID-19 research v0.192 CD4 Ivone Leong Mode of inheritance for gene: CD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.191 CDC42 Ivone Leong Classified gene: CDC42 as Green List (high evidence)
COVID-19 research v0.191 CDC42 Ivone Leong Gene: cdc42 has been classified as Green List (High Evidence).
COVID-19 research v0.190 CDC42 Ivone Leong gene: CDC42 was added
gene: CDC42 was added to Viral susceptibility. Sources: Expert Review
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42 were set to 31601675; 32303876; 32231661; 31271789
Phenotypes for gene: CDC42 were set to Neonatal-onset cytopaenia with dyshaematopoiesis; autoinflammation; rash; HLH
Review for gene: CDC42 was set to GREEN
Added comment: "PMID 31601675: four unrelated individuals with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. All shared the same de novo CDC42 variant (Chr1:22417990C>T, p.R186C). Another pair of sibs reported in PMID 32303876 with infantile myelofibrosis and myeloproliferation and same variant (parental mosaicism). Yet another individual in PMID 32231661 with different de novo variant, p.Cys81Tyr who in addition developed haematological malignancy and also had syndromic features, including ID. Note other missense variants in this gene cause Takenouchi-Kosaki syndrome, MIM# 616737 Sources: Literature
Zornitza Stark (Australian Genomics), 30 Apr 2020" - review copied from Primary immunodeficiency (Version 2.153)

"Comment on list classification: Gene added by Zornitza Stark (Australian Genomics) with a suggested Green rating based on evidence she has provided. As well as the listed cases there is another paper (PMID: 31271789) describing 4 unrelated cases with de novo variants in CDC42 (p.C188Y, p.R186C, p.*192C*24). The patients predominantly had systemic autoinflammatory disease and development of HLH. Therefore there is enough evidence to rate this gene as Green.
Ivone Leong (Genomics England Curator), 5 May 2020" - review copied from Primary immunodeficiency (Version 2.153)
Sources: Expert Review
COVID-19 research v0.189 KARS Sarah Leigh commented on gene: KARS: New gene name for KARS is KARS1
COVID-19 research v0.189 KARS Sarah Leigh Tag new-gene-name tag was added to gene: KARS.
COVID-19 research v0.189 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 WSCD1 Sarah Leigh reviewed gene: WSCD1: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 UNC5CL Sarah Leigh reviewed gene: UNC5CL: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 TAPT1 Sarah Leigh reviewed gene: TAPT1: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 SPNS3 Sarah Leigh reviewed gene: SPNS3: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 RPAIN Sarah Leigh reviewed gene: RPAIN: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 PROM1 Sarah Leigh reviewed gene: PROM1: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 PKD1L3 Sarah Leigh reviewed gene: PKD1L3: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 NUP88 Sarah Leigh reviewed gene: NUP88: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 MLKL Sarah Leigh reviewed gene: MLKL: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 MIS12 Sarah Leigh reviewed gene: MIS12: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 LDB2 Sarah Leigh reviewed gene: LDB2: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 KARS Sarah Leigh reviewed gene: KARS: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 HYDIN Sarah Leigh reviewed gene: HYDIN: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 CC2D2A Sarah Leigh reviewed gene: CC2D2A: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.189 BCAR1 Sarah Leigh reviewed gene: BCAR1: Rating: RED; Mode of pathogenicity: ; Publications: 32348764; Phenotypes: Influenza A Virus-Specific Antibody Responses; Mode of inheritance:
COVID-19 research v0.187 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to
COVID-19 research v0.187 WSCD1 Sarah Leigh gene: WSCD1 was added
gene: WSCD1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: WSCD1 was set to
COVID-19 research v0.187 UNC5CL Sarah Leigh gene: UNC5CL was added
gene: UNC5CL was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: UNC5CL was set to
COVID-19 research v0.187 TAPT1 Sarah Leigh gene: TAPT1 was added
gene: TAPT1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: TAPT1 was set to
COVID-19 research v0.187 SPNS3 Sarah Leigh gene: SPNS3 was added
gene: SPNS3 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: SPNS3 was set to
COVID-19 research v0.187 RPAIN Sarah Leigh gene: RPAIN was added
gene: RPAIN was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: RPAIN was set to
COVID-19 research v0.187 PROM1 Sarah Leigh gene: PROM1 was added
gene: PROM1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: PROM1 was set to
COVID-19 research v0.187 PKD1L3 Sarah Leigh gene: PKD1L3 was added
gene: PKD1L3 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: PKD1L3 was set to
COVID-19 research v0.187 NUP88 Sarah Leigh gene: NUP88 was added
gene: NUP88 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: NUP88 was set to
COVID-19 research v0.187 MLKL Sarah Leigh gene: MLKL was added
gene: MLKL was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: MLKL was set to
COVID-19 research v0.187 MIS12 Sarah Leigh gene: MIS12 was added
gene: MIS12 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: MIS12 was set to
COVID-19 research v0.187 LDB2 Sarah Leigh gene: LDB2 was added
gene: LDB2 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: LDB2 was set to
COVID-19 research v0.187 KARS Sarah Leigh gene: KARS was added
gene: KARS was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: KARS was set to
COVID-19 research v0.187 HYDIN Sarah Leigh gene: HYDIN was added
gene: HYDIN was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: HYDIN was set to
COVID-19 research v0.187 CC2D2A Sarah Leigh gene: CC2D2A was added
gene: CC2D2A was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: CC2D2A was set to
COVID-19 research v0.187 BCAR1 Sarah Leigh gene: BCAR1 was added
gene: BCAR1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: BCAR1 was set to
COVID-19 research v0.186 PIK3CG Ivone Leong Classified gene: PIK3CG as Green List (high evidence)
COVID-19 research v0.186 PIK3CG Ivone Leong Gene: pik3cg has been classified as Green List (High Evidence).
COVID-19 research v0.185 PIK3CG Ivone Leong gene: PIK3CG was added
gene: PIK3CG was added to Viral susceptibility. Sources: Expert list
Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3CG were set to 32001535; 31554793
Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis
Review for gene: PIK3CG was set to GREEN
Added comment: "Two individuals with complex immunological phenotypes reported and a mouse model. Sources: Literature
Zornitza Stark (Australian Genomics), 30 Apr 2020" - review copied from Primary immunodeficiency (Version 2.151).

"Comment on list classification: Gene added by Zornitza Stark (Australian Genomics) with recommended Green status based on provided evidence. There is enough evidence for this gene to be rated Green.
Ivone Leong (Genomics England Curator), 5 May 2020" - review copied from Primary immunodeficiency (Version 2.151).
Sources: Expert list
COVID-19 research v0.184 RIPK1 Ivone Leong Added comment: Comment on mode of inheritance: "Please note recent report of mono-allelic variants in two families.
Zornitza Stark (Australian Genomics), 30 Apr 2020" - review copied from Primary immunodeficiency (Version 2.150).

"Comment on mode of inheritance: MOI updated from Biallelic to Both monoallelic and biallelic based on new evidence provided by Zornitza Stark (Australian Genomics). PMID: 31827280.
Ivone Leong (Genomics England Curator), 5 May 2020" - review copied from Primary immunodeficiency (Version 2.150).
COVID-19 research v0.184 RIPK1 Ivone Leong Mode of inheritance for gene: RIPK1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.183 RIPK1 Ivone Leong Publications for gene: RIPK1 were set to 30026316
COVID-19 research v0.182 ITPKB Ivone Leong Classified gene: ITPKB as Amber List (moderate evidence)
COVID-19 research v0.182 ITPKB Ivone Leong Gene: itpkb has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.181 ITPKB Ivone Leong gene: ITPKB was added
gene: ITPKB was added to Viral susceptibility. Sources: Expert list
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPKB were set to 31987846; 14517551
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to AMBER
Added comment: "Single individual with homozygous bi-allelic LoF variant reported. Sources: Literature
Zornitza Stark (Australian Genomics), 1 May 2020" - review copied from Primary immunodeficiency panel (v2.147).

"Comment on list classification: Gene added by Zornitza Stark (Australian Genomics) with a recommended Red gene rating based on evidence provided. PMID: 31987846 describes a patient born of consanguineous Egyptian parents. The patient failed to thrive and had persistent thrush shortly after birth, recurrent pneumonias beginning at age 2 months, and Klebsiella pneumoniae skin abscesses at age 6 and 10 months. She had severe SCID.

PMID: 14517551 is a itpkb-/- mouse. Knockout of the gene caused a severe T cell deficiency. Based on these 2 pieces of information the gene has been given an Amber gene rating.
Ivone Leong (Genomics England Curator), 5 May 2020" - review copied from Primary immunodeficiency panel (v2.147).
Sources: Expert list
COVID-19 research v0.180 SMARCD2 Sophie Hambleton reviewed gene: SMARCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28369036; Phenotypes: neutropenia, specific granule deficiency, myelodysplasia, developmental delay, dysmorphic features; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.180 SLX4 Sophie Hambleton reviewed gene: SLX4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.180 SLC7A7 Sophie Hambleton reviewed gene: SLC7A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 10080182, 28057010, 21308987; Phenotypes: lysinuric protein intolerance, failure to thrive, hyperammonaemia, encephalopathy, developmental disability, nephropathy, lupus nephritis, haemophagocytic lymphophistiocytosis, pancreatitis, pulmonary alveolar proteinosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.180 SLC39A7 Sophie Hambleton reviewed gene: SLC39A7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: agammaglobulinaemia, B cell deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.180 SH3KBP1 Sophie Hambleton reviewed gene: SH3KBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypogammaglobulinaemia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
COVID-19 research v0.180 SH3BP2 Sophie Hambleton reviewed gene: SH3BP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.180 IL6 Sarah Leigh Classified gene: IL6 as Amber List (moderate evidence)
COVID-19 research v0.180 IL6 Sarah Leigh Gene: il6 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.179 IL6 Sarah Leigh changed review comment from: Strong association was observed between an IL6promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P?=?.0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P?=?.0046), whereas allele C homozygotes were underrepresented (P?=?.0062)(PMID 11001912).; to: Strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to Kaposi Sarcoma (KS) in HIV-infected men (P?=?.0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were over represented among patients with KS (P?=?.0046), whereas allele C homozygotes were under represented (P?=?.0062)(PMID 11001912).
COVID-19 research v0.179 ERCC4 Catherine Snow commented on gene: ERCC4
COVID-19 research v0.179 ABO Catherine Snow Phenotypes for gene: ABO were changed from to Virus susceptibility
COVID-19 research v0.178 ABO Catherine Snow Classified gene: ABO as Amber List (moderate evidence)
COVID-19 research v0.178 ABO Catherine Snow Added comment: Comment on list classification: Identified by expert review. Two preprints and publication relating to ABO and Sars-COV. https://doi.org/10.1101/2020.04.08.20058073 authors found that COVID-19 positive vs negative test results were increased in blood groups A and decreased in blood groups O, consistent with previous results from Wuhan and Shenzhen (https://doi.org/10.1101/2020.03.11.20031096)
COVID-19 research v0.178 ABO Catherine Snow Gene: abo has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.177 IFNG Sarah Leigh Phenotypes for gene: IFNG were changed from to {AIDS, rapid progression to} 609423
COVID-19 research v0.176 TNF Sarah Leigh reviewed gene: TNF: Rating: RED; Mode of pathogenicity: ; Publications: 12915457; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 TLR2 Sarah Leigh reviewed gene: TLR2: Rating: RED; Mode of pathogenicity: ; Publications: 17085599; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 SERPINA1 Sarah Leigh reviewed gene: SERPINA1: Rating: RED; Mode of pathogenicity: ; Publications: 11527807; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 SCN5A Sarah Leigh reviewed gene: SCN5A: Rating: RED; Mode of pathogenicity: ; Publications: 25368329; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 RB1 Sarah Leigh reviewed gene: RB1: Rating: RED; Mode of pathogenicity: ; Publications: 2968522, 18467589; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 PDCD1 Sarah Leigh reviewed gene: PDCD1: Rating: RED; Mode of pathogenicity: ; Publications: 16921384; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 NUP214 Sarah Leigh reviewed gene: NUP214: Rating: RED; Mode of pathogenicity: ; Publications: 31178128; Phenotypes: {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 MET Sarah Leigh reviewed gene: MET: Rating: RED; Mode of pathogenicity: ; Publications: 9927037; Phenotypes: Hepatocellular carcinoma, childhood type, somatic 114550; Mode of inheritance: Unknown
COVID-19 research v0.176 LDLR Sarah Leigh reviewed gene: LDLR: Rating: GREEN; Mode of pathogenicity: ; Publications: 10535997, 32268133, 31386864, 31358055; Phenotypes: Hypercholesterolemia, familial, 1 143890, LDL cholesterol level QTL2 143890; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research v0.176 KRT18 Sarah Leigh reviewed gene: KRT18: Rating: RED; Mode of pathogenicity: ; Publications: 8770877; Phenotypes: {Cirrhosis, noncryptogenic, susceptibility to} 215600, Cirrhosis, cryptogenic 215600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 IRGM Sarah Leigh reviewed gene: IRGM: Rating: RED; Mode of pathogenicity: ; Publications: 11457893; Phenotypes: murine cytomegalovirus infection; Mode of inheritance:
COVID-19 research v0.176 IL6 Sarah Leigh reviewed gene: IL6: Rating: GREEN; Mode of pathogenicity: ; Publications: 11001912; Phenotypes: {Kaposi sarcoma, susceptibility to} 148000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.176 IL4R Sarah Leigh reviewed gene: IL4R: Rating: RED; Mode of pathogenicity: ; Publications: 16189667; Phenotypes: {AIDS, slow progression to} 609423; Mode of inheritance:
COVID-19 research v0.176 IFNG Sarah Leigh reviewed gene: IFNG: Rating: AMBER; Mode of pathogenicity: ; Publications: 12854077; Phenotypes: AIDS, rapid progression to} 609423; Mode of inheritance: Unknown
COVID-19 research v0.176 IFITM3 Sarah Leigh reviewed gene: IFITM3: Rating: GREEN; Mode of pathogenicity: ; Publications: 22446628, 18505827, 32348495; Phenotypes: {Influenza, severe, susceptibility to} 614680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 ICAM1 Sarah Leigh reviewed gene: ICAM1: Rating: RED; Mode of pathogenicity: ; Publications: 2538243, 12853962; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 HTR2A Sarah Leigh reviewed gene: HTR2A: Rating: RED; Mode of pathogenicity: ; Publications: 15550673; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 HLA-DQB1 Sarah Leigh reviewed gene: HLA-DQB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 23710940, 10609818, 12473762; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.176 HLA-C Sarah Leigh reviewed gene: HLA-C: Rating: RED; Mode of pathogenicity: ; Publications: 19935663, 21051598; Phenotypes: {HIV-1 viremia, susceptibility to} 609423; Mode of inheritance: Unknown
COVID-19 research v0.176 HFE Sarah Leigh reviewed gene: HFE: Rating: RED; Mode of pathogenicity: ; Publications: 16043695; Phenotypes: Hemochromatosis 235200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 HBB Sarah Leigh reviewed gene: HBB: Rating: RED; Mode of pathogenicity: ; Publications: 8168595, 2599880, 8602627; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.176 DMD Sarah Leigh reviewed gene: DMD: Rating: RED; Mode of pathogenicity: ; Publications: 10753926, 12118246; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
COVID-19 research v0.176 CYP2B6 Sarah Leigh reviewed gene: CYP2B6: Rating: RED; Mode of pathogenicity: ; Publications: 15622315, 20860463, 15194512, 23418033; Phenotypes: {Efavirenz central nervous system toxicity, susceptibility to} 614546, Efavirenz, poor metabolism of 614546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 CX3CR1 Sarah Leigh reviewed gene: CX3CR1: Rating: AMBER; Mode of pathogenicity: ; Publications: 14607932, 10731151; Phenotypes: {Rapid progression to AIDS from HIV1 infection} 609423; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.176 CR1 Sarah Leigh reviewed gene: CR1: Rating: RED; Mode of pathogenicity: ; Publications: 16517720; Phenotypes: acute myocarditis and pericardial fibrosis due to coxsackievirus B3; Mode of inheritance: Unknown
COVID-19 research v0.176 CPT2 Sarah Leigh reviewed gene: CPT2: Rating: AMBER; Mode of pathogenicity: ; Publications: 15811315, 18306170, 20934285, 21697855; Phenotypes: {Encephalopathy, acute, infection-induced, 4, susceptibility to} 614212; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.176 CD209 Sarah Leigh reviewed gene: CD209: Rating: RED; Mode of pathogenicity: ; Publications: 15564514, 15838506, 16379498; Phenotypes: {Dengue fever, protection against} 614371, {HIV type 1, susceptibility to} 609423, {Mycobacterium tuberculosis, susceptibility to} 607948; Mode of inheritance: Unknown
COVID-19 research v0.176 CCR5 Sarah Leigh reviewed gene: CCR5: Rating: RED; Mode of pathogenicity: ; Publications: 16418398, 16418398, 9132277; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.176 CCND1 Sarah Leigh reviewed gene: CCND1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: {Colorectal cancer, susceptibility to} 114500, {von Hippel-Lindau syndrome, modifier of} 193300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.176 CCL3L1 Sarah Leigh reviewed gene: CCL3L1: Rating: RED; Mode of pathogenicity: ; Publications: 15637236, 15637236, 19812560, 19812561, 19812562; Phenotypes: {HIV/AIDS, susceptibility to} 609423; Mode of inheritance: Unknown
COVID-19 research v0.175 IFITM3 Ivone Leong Mode of inheritance for gene: IFITM3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.175 IFITM3 Ivone Leong Mode of inheritance for gene: IFITM3 was changed from to BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.174 IFITM3 Ivone Leong Phenotypes for gene: IFITM3 were changed from to {Influenza, severe, susceptibility to}, 614680
COVID-19 research v0.173 IFITM3 Ivone Leong Classified gene: IFITM3 as Green List (high evidence)
COVID-19 research v0.173 IFITM3 Ivone Leong Added comment: Comment on list classification: PMID: 32348495 reports that individuals who are homozygous for the C allele of rs12252 SNP in IFITM3 is associated with more severe disease in older patients. This SNP is common in Asian populations (MAF reported on dbSNP for East Asians: 0.57; Europeans: 0.0546). This study was condicted in China with 80 patients who were confirmed to be positive for COVID-19.

PMID: 23361009 found that homozygous C allele of rs12252 is in 69% of Chinese patients who were infected with severe pandemic influenza A H1N1/09 virus infection compared with 25% who had mild infection. The homozygous C allele for rs12252 is associated with a 6-fold greater risk for severe infection than CT and TT genotypes.

Based on these studies there is enough evidence to promote this gene to Green status.
COVID-19 research v0.173 IFITM3 Ivone Leong Gene: ifitm3 has been classified as Green List (High Evidence).
COVID-19 research v0.172 IFITM3 Ivone Leong Publications for gene: IFITM3 were set to
COVID-19 research v0.171 SEC61A1 Sophie Hambleton reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28782633, 32325141; Phenotypes: Hypogammaglobulinaemia, recurrent infections, plasma cell deficiency, severe congenital neutropenia, tubulointerstitial and Glomerulocystic Kidney Disease with Anemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research v0.171 RNU4ATAC Sophie Hambleton reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 RFWD3 Sophie Hambleton reviewed gene: RFWD3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 RELA Sophie Hambleton reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: chronic mucocutaneous ulceration, autoimmune lymphoporliferative syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.171 REL Sophie Hambleton reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: combined immunodeficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 RANBP2 Sophie Hambleton reviewed gene: RANBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: necrotizing encephalopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.171 PSMG2 Sophie Hambleton reviewed gene: PSMG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30664889; Phenotypes: CANDLE syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 RAD51C Sophie Hambleton reviewed gene: RAD51C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 RAD51 Sophie Hambleton reviewed gene: RAD51: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 POLR3F Sophie Hambleton reviewed gene: POLR3F: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 POLR3C Sophie Hambleton reviewed gene: POLR3C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 POLR3A Sophie Hambleton reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 POLD2 Sophie Hambleton reviewed gene: POLD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: combined immunodeficiency, neurodevelopmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 POLD1 Sophie Hambleton changed review comment from: IUIS gene. Biallelic missense variant p.R1060C, that impairs association between POLD1 and POLD2, was associated with combined immunodeficiency in 3 affected members of one kindred. Allelic AD disorders cause alternative phenotypes; to: IUIS gene. Biallelic missense variant p.R1060C, that impairs association between POLD1 and POLD2, was associated with combined immunodeficiency in 3 affected members of one kindred. An unrelated case of combined immunodeficiency reported elsewhere (PMID 31449058) had 3 rare missense variants. Allelic AD disorders cause alternative phenotypes
COVID-19 research v0.171 POLD1 Sophie Hambleton reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: combined immunodeficiency, T-cell lymphopenia, recurrent infections, hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 PAX1 Sophie Hambleton reviewed gene: PAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: severe combined immunodeficiency, thymic aplasia, otofaciocervical syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 PALB2 Sophie Hambleton reviewed gene: PALB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 OAS1 Sophie Hambleton reviewed gene: OAS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile-Onset Pulmonary Alveolar Proteinosis, Hypogammaglobulinemia.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.171 NOS2 Sophie Hambleton reviewed gene: NOS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 NFE2L2 Sophie Hambleton reviewed gene: NFE2L2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: growth retardation, developmental delay, leukodystrophy, recurrent infections, hypogammaglobulinaemia, hypohomocysteinaemia, increased G-6-P-dehydrogenase activity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.171 MAD2L2 Sophie Hambleton reviewed gene: MAD2L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 IRF9 Sophie Hambleton reviewed gene: IRF9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 IRF4 Sophie Hambleton reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Whipple's disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research v0.171 IL6ST Sophie Hambleton reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: None; Publications: 31914175, 32207811; Phenotypes: recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, impaired acute-phase response, stuve-wiedemann syndrome, craniosynostosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
COVID-19 research v0.171 IL6R Sophie Hambleton reviewed gene: IL6R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Impaired humoral immunity, hyper-IgE, recurrent infections, eczema; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 IL2RB Sophie Hambleton reviewed gene: IL2RB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: very early onset inflammatory bowel disease, CMV disease, dermatitis, immune dysregulation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 IL12RB2 Sophie Hambleton changed review comment from: IUIS gene; to: IUIS gene for MSMD, incomplete penetrance
see PMID 30578351
COVID-19 research v0.171 IL23R Sophie Hambleton reviewed gene: IL23R: Rating: ; Mode of pathogenicity: None; Publications: 30578351; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 IL18BP Sophie Hambleton reviewed gene: IL18BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 IL12RB2 Sophie Hambleton reviewed gene: IL12RB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 IFNAR1 Sophie Hambleton reviewed gene: IFNAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Viral susceptibility, disseminated MMR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 HLA-DRB1 Sophie Hambleton reviewed gene: HLA-DRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Other
COVID-19 research v0.171 HLA-B Sophie Hambleton reviewed gene: HLA-B: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 HAVCR2 Sophie Hambleton reviewed gene: HAVCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Panniculitis, T-cell lymphoma, haemophagocytic lymphohistiocytosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.171 FERMT1 Sophie Hambleton reviewed gene: FERMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.171 IRF7 Rebecca Foulger Publications for gene: IRF7 were set to 26761402; 9315633; 32086639; 25814066; 32048120; 26621750; 31154625
COVID-19 research v0.170 IRF7 Rebecca Foulger Publications for gene: IRF7 were set to 26761402; 9315633; 32086639; 25814066; 32048120; 26621750
COVID-19 research v0.169 PAX1 Rebecca Foulger Classified gene: PAX1 as Green List (high evidence)
COVID-19 research v0.169 PAX1 Rebecca Foulger Gene: pax1 has been classified as Green List (High Evidence).
COVID-19 research v0.168 PAX1 Rebecca Foulger gene: PAX1 was added
gene: PAX1 was added to Viral susceptibility. Sources: Other,Literature
Mode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAX1 were set to 28657137; 32111619
Phenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560; Syndromic SCID
Added comment: Added PAX1 to Viral susceptibility panel as Green to match recent addition of PAX1 to Primary immunodeficiency panel (Version 2.137).
Sources: Other, Literature
COVID-19 research v0.167 TP53 Sarah Leigh reviewed gene: TP53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.167 TP53 Sarah Leigh Publications for gene: TP53 were set to 32086639; 32048120
COVID-19 research v0.166 CIB1 Sarah Leigh reviewed gene: CIB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.166 CIB1 Sarah Leigh Phenotypes for gene: CIB1 were changed from Epidermodysplasia verruciformis; Defects in intrinsic and innate immunity; CIB1 deficiency to Epidermodysplasia verruciformis 3 618267; Defects in intrinsic and innate immunity; CIB1 deficiency
COVID-19 research v0.165 ACE2 Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.22.056127v1 show that ACE2 levels in the respiratory tract did not increase in association with risk factors for severe COVID-19 (e.g. age and underlying chronic comorbidities).
COVID-19 research v0.165 TMPRSS2 Rebecca Foulger commented on gene: TMPRSS2: Preprint http://biorxiv.org/cgi/content/short/2020.04.23.057190 analysed coding region variants in TMPRSS2 and the eQTL variants which may affect gene experssion. They suggest that lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations. In particular, we found that the regulatory region variant rs35074065 is associated with high expression of TMPRSS2 (but lower expression of MX1).
COVID-19 research v0.165 ACE2 Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.050534v1 conclude that higher expression of ACE2 facilitated by natural variations (with different frequencies in different populations) results in ACE2 homo-dimerization which is disadvantageous for TMPRSS2 mediated cleavage of ACE2. They propose that monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein.
COVID-19 research v0.165 STAT2 Rebecca Foulger commented on gene: STAT2
COVID-19 research v0.165 TMPRSS2 Rebecca Foulger commented on gene: TMPRSS2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.056259v2 suggests that ACE2 and TMPRSS2 co-expression in the prostate may explain sex differences in the observed COVID-19 disaparities.
COVID-19 research v0.165 ACE2 Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.056259v2 suggests that ACE2 and TMPRSS2 co-expression in the prostate may explain sex differences in the observed COVID-19 disaparities.
COVID-19 research v0.165 IL18BP Rebecca Foulger commented on gene: IL18BP
COVID-19 research v0.165 IL18BP Rebecca Foulger Publications for gene: IL18BP were set to 32086639; 32048120; PubMed: 31213488
COVID-19 research v0.164 CCR5 Ivone Leong Phenotypes for gene: CCR5 were changed from to {West nile virus, susceptibility to}, 610379; {HIV infection, susceptibility/resistance to}
COVID-19 research v0.163 FCHO1 Sophie Hambleton reviewed gene: FCHO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30822429, 32098969; Phenotypes: combined immunodeficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 FANCM Sophie Hambleton reviewed gene: FANCM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCL Sophie Hambleton reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCI Sophie Hambleton reviewed gene: FANCI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, bone marrow failure; Mode of inheritance: None
COVID-19 research v0.163 FANCG Sophie Hambleton reviewed gene: FANCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCF Sophie Hambleton reviewed gene: FANCF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, bone marrow failure; Mode of inheritance: None
COVID-19 research v0.163 FANCE Sophie Hambleton reviewed gene: FANCE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCD2 Sophie Hambleton reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCC Sophie Hambleton reviewed gene: FANCC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 FANCB Sophie Hambleton reviewed gene: FANCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, bone marrow failure; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
COVID-19 research v0.163 FANCA Sophie Hambleton reviewed gene: FANCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 ERCC4 Sophie Hambleton reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: xeroderma pigmentosum, Fanconi anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 ERBIN Sophie Hambleton reviewed gene: ERBIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 TMPRSS2 Rebecca Foulger commented on gene: TMPRSS2: Preprint https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 Lopera et al shows a LACK of association between genetic variants at ACE2 and TMPRSS2 and human quantitative phenotypes. The authors recognise that the SARS-CoV-2 virus uses ACE2 for cell invasion, and the serine protease TMPRSS2 for S protein priming and therefore they investigated whether genetic variation in these two genes modulates an individual's genetic predisposition to infection and virus clearance. They examined 178 quantitative phenotypes in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2: none reached the threshold for significance though these variants may play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases.
COVID-19 research v0.163 ACE2 Rebecca Foulger commented on gene: ACE2: Preprint https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 Lopera et al shows a LACK of association between genetic variants at ACE2 and TMPRSS2 and human quantitative phenotypes. The authors recognise that the SARS-CoV-2 virus uses ACE2 for cell invasion, and the serine protease TMPRSS2 for S protein priming and therefore they investigated whether genetic variation in these two genes modulates an individual's genetic predisposition to infection and virus clearance. They examined 178 quantitative phenotypes in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2: none reached the threshold for significance though these variants may play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases.
COVID-19 research v0.163 EFL1 Sophie Hambleton reviewed gene: EFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 DEF6 Sophie Hambleton reviewed gene: DEF6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, combined immunodeficiency, autoimmunity, autoimmune enteropathy, dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 DBR1 Sophie Hambleton reviewed gene: DBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29474921; Phenotypes: Susceptibility to viral encephalitis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 BRIP1 Sophie Hambleton reviewed gene: BRIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 CIB1 Sophie Hambleton reviewed gene: CIB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 C17orf62 Sophie Hambleton reviewed gene: C17orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: chronic granulomatous disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.163 CCL2 Sophie Hambleton reviewed gene: CCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.163 ARHGEF1 Sophie Hambleton reviewed gene: ARHGEF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.163 ALPI Sophie Hambleton reviewed gene: ALPI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: inflammatory bowel disease; Mode of inheritance: None
COVID-19 research v0.163 ACE2 Sophie Hambleton reviewed gene: ACE2: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.163 CTSB Eleanor Williams changed review comment from: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
I cannot find reference to the gene in the two publications listed though PMID: 32142651 and 32015507.
Sources: Other; to: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
PMID: 32142651 - Hoffman et al 2020 - Cell journal - CatB/L involved in S protein priming.
COVID-19 research v0.163 CTSL Eleanor Williams changed review comment from: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
I cannot find reference to the gene in the two publications listed though PMID: 32142651 and 32015507.
Sources: Other; to: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
PMID: 32142651 - Hoffman et al 2020 - Cell journal - CatB/L involved in S protein priming.
COVID-19 research v0.163 CTSL Eleanor Williams gene: CTSL was added
gene: CTSL was added to Viral susceptibility. Sources: Other
Mode of inheritance for gene: CTSL was set to Unknown
Added comment: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
I cannot find reference to the gene in the two publications listed though PMID: 32142651 and 32015507.
Sources: Other
COVID-19 research v0.162 CTSB Eleanor Williams gene: CTSB was added
gene: CTSB was added to Viral susceptibility. Sources: Other
Mode of inheritance for gene: CTSB was set to Unknown
Added comment: The Covid-19 cell atlas (https://www.covid19cellatlas.org/) lists this gene as a COVID-19/SARS-CoV-2 entry-associated gene.
I cannot find reference to the gene in the two publications listed though PMID: 32142651 and 32015507.
Sources: Other
COVID-19 research v0.161 ACE2 Eleanor Williams changed review comment from: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.; to: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

PMID: 32142651 - Hoffman et al 2020 - demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry
COVID-19 research v0.161 ACE2 Eleanor Williams Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651
COVID-19 research v0.160 ACE2 Eleanor Williams edited their review of gene: ACE2: Added comment: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.; Changed publications: 32015507
COVID-19 research v0.160 ABO Owen Siggs gene: ABO was added
gene: ABO was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: ABO was set to Other
Publications for gene: ABO were set to 15784866
Review for gene: ABO was set to AMBER
Added comment: Preliminary suggestion from preprints (https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v2 & https://www.preprints.org/manuscript/202003.0356/v1) that ABO blood group may influence susceptibility to SARS-CoV-2 infection. Other preliminary evidence that ABO blood group may also influence susceptibility to SARS-CoV infection (PMID: 15784866). Both yet to be replicated, but suggest individuals of blood group O to be at lower risk of infection.
Sources: Literature
COVID-19 research v0.160 TLR3 Abdelazeem Elhabyan edited their review of gene: TLR3: Added comment: I forgot to add severe influenza pneumonia in the associated phenotype in the previous comment; Changed phenotypes: Herpes simplex encephalitis predisposition , severe influenza Pneumonia ,HIV resistance to infection
COVID-19 research v0.160 TLR3 Abdelazeem Elhabyan changed review comment from: These studies demonstrate the deleterious effect of some TLR3 mutations and predisposition to Herpes simplex encephalitis in 4 separate studies on unrelated patients from different countries. TLR3 mutations in 3 children were associated with severe influenza pneumonitis. Finally, 2 other studies evaluate the protective effect of a common polymorphism of TLR3 against HIV infection in repetitively exposed individuals. Accordingly, we might find protective or deleterious effects in COVID19 patients due to different mutations of TLR3.

TLR3 is a receptor for dsRNA (intermediate in the replication of many viruses including HSV) which induces IFN response to prevent the cytopathic effects of different viruses. A heterozygous dominant-negative mutation of TLR3 was discovered in 2 unrelated children with HSE. TLR3 mutant fibroblasts from the 2 patients were infected by HSV-1 and vesicular stomatitis virus(VSV).IFNB and IFNL production were impaired in those cells, viral replication was higher and cell survival was lower in the 2 patients' cells when compared with the controls. Blood leukocyte response normally with to poly (I:C) which explains why the disease is not disseminated and also explains the redundant role of TLR3 in blood cells(13).
Similar findings were reported in a polish child in 2011, however, the patient here was compound heterozygous for a missense mutation leading to autosomal recessive inheritance of TLR3 deficiency(14).
Treatment with IFN alpha and beta canceled the effect of the dominant-negative mutation increasing the causality relationship between TLR3 mutants and viral immune response(13).
Relatives of the 2 patients with the same mutation did not show decreased interferon response nor they showed HSE as a complication of HSV which means that this mutation does not have full penetrance(13).

In another study, 110 patients with HSE were sequenced (exons of TLR3) to establish a new association of TLR3 mutations and HSE. The study reported 5 novel variants other than those previously described in the literature. 2 of them were not pathogenically demonstrated by in vitro studies while 3 of them were pathogenic with similar findings to those described above. Additionally, they found 3 patients with the same mutations previously described in the literature so the total of patients with deleterious TLR3 mutations would be 6 out of 110. 4 of those 6 patients(66%) with TLR6 mutations had a relapse In contrast to 12 out of 120(total cohort) (10%)(15).

In a recent study done on 16 patients with adult-onset HSE using whole-exome sequencing(WES), 1 patient was discovered to have TLR3 deficiency, while 8 other patients had mutations in other genes in the TLR3 pathway(2 patients with a mutation in IRF3, 2 patients with mutations in STAT1, 2 patients with mutations in TRIF, 1 patient with a mutation in TYK2,1 patients with a mutation in MAVS, and finally 1 patient with a mutation in TBK1)(16)

A common polymorphism in TLR3(rs3775291) was linked to increased resistance to HIV1 infection by the genotyping study of Spanish and Italian cohorts with a P value of .023 and .029 respectively. The study compared HIV exposed seronegative cohort(IV drug abuse and sexually active ) with controls. Repetitive HIV exposure in the cohort was evidenced by HCV seropositivity. In vitro infection of PBMCs with HIV showed increased resistance in cells carrying the allele and also TLR3 stimulation by TLR3 agonists showed an increased level of expression of CD69, IL-6, and CCL3(17).

A similar study was conducted on the Caucasian population showing the protective effect of the allele against HIV infection(18).

Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-β and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients’ iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I, and/or III IFN–mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature(PMID: 31217193
)




13.Zhang SY, Jouanguy E, Ugolini S, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007;317(5844):1522–1527. doi:10.1126/science.1139522

14.Guo Y, Audry M, Ciancanelli M, et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med. 2011;208(10):2083–2098. doi:10.1084/jem.20101568

15.Lim HK, Seppänen M, Hautala T, et al. TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk. Neurology. 2014;83(21):1888–1897. doi:10.1212/WNL.0000000000000999

16.Mørk N, Kofod-Olsen E, Sørensen KB, et al. Mutations in the TLR3 signaling pathway and beyond in adult patients with herpes simplex encephalitis. Genes Immun. 2015;16(8):552–566. doi:10.1038/gene.2015.46

17.Sironi M, Biasin M, Cagliani R, et al. A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. J Immunol. 2012;188(2):818–823. doi:10.4049/jimmunol.1102179

18.Huik K, Avi R, Pauskar M, et al. Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users. Infect Genet Evol. 2013;20:78–82. doi:10.1016/j.meegid.2013.08.008

19.Lim HK, Huang SXL, Chen J, et al. Severe influenza pneumonitis in children with inherited TLR3 deficiency. J Exp Med. 2019;216(9):2038–2056. doi:10.1084/jem.20181621; to: These studies demonstrate the deleterious effect of some TLR3 mutations and predisposition to Herpes simplex encephalitis in 4 separate studies on unrelated patients from different countries. TLR3 mutations in 3 children were associated with severe influenza pneumonitis. Finally, 2 other studies evaluate the protective effect of a common polymorphism of TLR3 against HIV infection in repetitively exposed individuals. Accordingly, we might find protective or deleterious effects in COVID19 patients due to different mutations of TLR3.

TLR3 is a receptor for dsRNA (intermediate in the replication of many viruses including HSV) which induces IFN response to prevent the cytopathic effects of different viruses. A heterozygous dominant-negative mutation of TLR3 was discovered in 2 unrelated children with HSE. TLR3 mutant fibroblasts from the 2 patients were infected by HSV-1 and vesicular stomatitis virus(VSV).IFNB and IFNL production were impaired in those cells, viral replication was higher and cell survival was lower in the 2 patients' cells when compared with the controls. Blood leukocyte response normally with to poly (I:C) which explains why the disease is not disseminated and also explains the redundant role of TLR3 in blood cells(13).
Similar findings were reported in a polish child in 2011, however, the patient here was compound heterozygous for a missense mutation leading to autosomal recessive inheritance of TLR3 deficiency(14).
Treatment with IFN alpha and beta canceled the effect of the dominant-negative mutation increasing the causality relationship between TLR3 mutants and viral immune response(13).
Relatives of the 2 patients with the same mutation did not show decreased interferon response nor they showed HSE as a complication of HSV which means that this mutation does not have full penetrance(13).

In another study, 110 patients with HSE were sequenced (exons of TLR3) to establish a new association of TLR3 mutations and HSE. The study reported 5 novel variants other than those previously described in the literature. 2 of them were not pathogenically demonstrated by in vitro studies while 3 of them were pathogenic with similar findings to those described above. Additionally, they found 3 patients with the same mutations previously described in the literature so the total of patients with deleterious TLR3 mutations would be 6 out of 110. 4 of those 6 patients(66%) with TLR6 mutations had a relapse In contrast to 12 out of 120(total cohort) (10%)(15).

In a recent study done on 16 patients with adult-onset HSE using whole-exome sequencing(WES), 1 patient was discovered to have TLR3 deficiency, while 8 other patients had mutations in other genes in the TLR3 pathway(2 patients with a mutation in IRF3, 2 patients with mutations in STAT1, 2 patients with mutations in TRIF, 1 patient with a mutation in TYK2,1 patients with a mutation in MAVS, and finally 1 patient with a mutation in TBK1)(16)

A common polymorphism in TLR3(rs3775291) was linked to increased resistance to HIV1 infection by the genotyping study of Spanish and Italian cohorts with a P value of .023 and .029 respectively. The study compared HIV exposed seronegative cohort(IV drug abuse and sexually active ) with controls. Repetitive HIV exposure in the cohort was evidenced by HCV seropositivity. In vitro infection of PBMCs with HIV showed increased resistance in cells carrying the allele and also TLR3 stimulation by TLR3 agonists showed an increased level of expression of CD69, IL-6, and CCL3(17).

A similar study was conducted on the Caucasian population showing the protective effect of the allele against HIV infection(18).

Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-β and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients’ iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I, and/or III IFN–mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature(PMID: 31217193
)




13.Zhang SY, Jouanguy E, Ugolini S, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007;317(5844):1522–1527. doi:10.1126/science.1139522

14.Guo Y, Audry M, Ciancanelli M, et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med. 2011;208(10):2083–2098. doi:10.1084/jem.20101568

15.Lim HK, Seppänen M, Hautala T, et al. TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk. Neurology. 2014;83(21):1888–1897. doi:10.1212/WNL.0000000000000999

16.Mørk N, Kofod-Olsen E, Sørensen KB, et al. Mutations in the TLR3 signaling pathway and beyond in adult patients with herpes simplex encephalitis. Genes Immun. 2015;16(8):552–566. doi:10.1038/gene.2015.46

17.Sironi M, Biasin M, Cagliani R, et al. A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. J Immunol. 2012;188(2):818–823. doi:10.4049/jimmunol.1102179

18.Huik K, Avi R, Pauskar M, et al. Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users. Infect Genet Evol. 2013;20:78–82. doi:10.1016/j.meegid.2013.08.008

19.Lim HK, Huang SXL, Chen J, et al. Severe influenza pneumonitis in children with inherited TLR3 deficiency. J Exp Med. 2019;216(9):2038–2056. doi:10.1084/jem.20181621
COVID-19 research v0.160 TLR3 Abdelazeem Elhabyan reviewed gene: TLR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Herpes simplex encephalitis predisposition , HIV resistance to infection; Mode of inheritance: Other
COVID-19 research v0.160 UNC93B1 Abdelazeem Elhabyan reviewed gene: UNC93B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Other
COVID-19 research v0.160 PHB2 Rebecca Foulger gene: PHB2 was added
gene: PHB2 was added to Viral susceptibility. Sources: Other,Literature
Mode of inheritance for gene: PHB2 was set to Unknown
Added comment: Added to panel based on presence in UniProt COVID portal: https://covid-19.uniprot.org/uniprotkb/Q99623
Sources: Other, Literature
COVID-19 research v0.159 DDX1 Rebecca Foulger gene: DDX1 was added
gene: DDX1 was added to Viral susceptibility. Sources: Other,Literature
Mode of inheritance for gene: DDX1 was set to Unknown
Publications for gene: DDX1 were set to 20573827
Added comment: Added to panel based on presence in UniProt COVID portal: https://covid19.uniprot.org/uniprotkb/Q92499. The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication (PMID:20573827).
Sources: Other, Literature
COVID-19 research v0.158 MPP5 Rebecca Foulger gene: MPP5 was added
gene: MPP5 was added to Viral susceptibility. Sources: Other,Literature
Mode of inheritance for gene: MPP5 was set to Unknown
Publications for gene: MPP5 were set to 20861307
Added comment: Added to panel based on presence in the UniProt COVID portal (https://covid-19.uniprot.org/uniprotkb/Q8N3R9). Acts as an interaction partner for human SARS coronavirus envelope protein E (MPP5 aka PALS1) (PMID:20861307).
Sources: Other, Literature
COVID-19 research v0.157 SMAD3 Rebecca Foulger gene: SMAD3 was added
gene: SMAD3 was added to Viral susceptibility. Sources: Other,Literature
Mode of inheritance for gene: SMAD3 was set to Unknown
Publications for gene: SMAD3 were set to 18055455
Added comment: Added to panel based on presence in the UniProt COVID portal: https://covid-19.uniprot.org/uniprotkb/P84022. SMAD3 interacts with SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein (PMID:18055455).
Sources: Other, Literature
COVID-19 research v0.156 CCL11 Sarah Leigh Publications for gene: CCL11 were set to
COVID-19 research v0.155 CCL11 Sarah Leigh Classified gene: CCL11 as Red List (low evidence)
COVID-19 research v0.155 CCL11 Sarah Leigh Added comment: Comment on list classification: A cytokine (inflammatory biomarker), that is released in response to viral infections. Increased levels of CCL11 amongst other cytokines, is associated with immunity to West Nile virus (PMID 30915442). A haplotype that included c.-1385G>A was associated with resistance to HIV-1 infection (PMID 14571188).
COVID-19 research v0.155 CCL11 Sarah Leigh Gene: ccl11 has been classified as Red List (Low Evidence).
COVID-19 research v0.154 PHB Rebecca Foulger gene: PHB was added
gene: PHB was added to Viral susceptibility. Sources: Other
Mode of inheritance for gene: PHB was set to Unknown
Added comment: Added to panel based on presence in the UniProt COVID portal: https://covid-19.uniprot.org/uniprotkb/P35232.
Sources: Other
COVID-19 research v0.153 ITGAL Rebecca Foulger gene: ITGAL was added
gene: ITGAL was added to Viral susceptibility. Sources: Literature,Other
Mode of inheritance for gene: ITGAL was set to Unknown
Publications for gene: ITGAL were set to 18020948
Added comment: Added to panel based on presence in the UniProt COVID portal:
https://covid-19.uniprot.org/uniprotkb/P20701. Data in PMID:18020948 suggests ITGAL (LFA-1) to be an attachment factor or the receptor for SARS-CoV on human leukocytes. Kept rating as Red awaiting Expert Review.
Sources: Literature, Other
COVID-19 research v0.152 SGTA Rebecca Foulger Classified gene: SGTA as Red List (low evidence)
COVID-19 research v0.152 SGTA Rebecca Foulger Added comment: Comment on list classification: Kept rating as Red awaiting expert review. Role for protein in viral infection, but no population studies/SNP analyses yet.
COVID-19 research v0.152 SGTA Rebecca Foulger Gene: sgta has been classified as Red List (Low Evidence).
COVID-19 research v0.151 SGTA Rebecca Foulger gene: SGTA was added
gene: SGTA was added to Viral susceptibility. Sources: Other
Mode of inheritance for gene: SGTA was set to Unknown
Publications for gene: SGTA were set to 28356524; 24675744
Added comment: Added to panel based on presence in the UniProt COVID portal (https://covid-19.uniprot.org/uniprotkb/O43765). In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via protein interactions.
Sources: Other
COVID-19 research v0.150 ADAM17 Rebecca Foulger Publications for gene: ADAM17 were set to 22010916; 20603312; 25058236; 32086639; 11149563; 28930861; 32048120; 25171914
COVID-19 research v0.149 ACE2 Rebecca Foulger Classified gene: ACE2 as Green List (high evidence)
COVID-19 research v0.149 ACE2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Multiple functional data demonstrates a role for ACE2 as a receptor for Coronaviruses. Plus a vast amount of preprint data that suggests SNPs in ACE2 should be explored for regional differences.
COVID-19 research v0.149 ACE2 Rebecca Foulger Gene: ace2 has been classified as Green List (High Evidence).
COVID-19 research v0.148 TMPRSS2 Rebecca Foulger Classified gene: TMPRSS2 as Green List (high evidence)
COVID-19 research v0.148 TMPRSS2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green on this research panel: Known mechanisms for involvement in viral infection (including proteolytic cleavage of the viral receptor, ACE2) plus variants identified in preprints as candidates for COVID-19 severity.
COVID-19 research v0.148 TMPRSS2 Rebecca Foulger Gene: tmprss2 has been classified as Green List (High Evidence).
COVID-19 research v0.147 TMPRSS2 Rebecca Foulger commented on gene: TMPRSS2
COVID-19 research v0.147 TMPRSS2 Rebecca Foulger Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843
COVID-19 research v0.146 TMPRSS2 Rebecca Foulger Publications for gene: TMPRSS2 were set to 31488196
COVID-19 research v0.145 ACE2 Rebecca Foulger commented on gene: ACE2: ACE2 gene present in the UniProt COVID portal (https://covid-19.uniprot.org/ 6-April-2020) which provides the latest available pre-release UniProtKB data for the SARS-CoV-2 coronavirus and other entries relating to the COVID-19 outbreak.
COVID-19 research v0.145 IL23A Rebecca Foulger commented on gene: IL23A
COVID-19 research v0.145 IL23A Rebecca Foulger Publications for gene: IL23A were set to
COVID-19 research v0.144 IL22 Rebecca Foulger Classified gene: IL22 as Red List (low evidence)
COVID-19 research v0.144 IL22 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Red: mouse model in PMID:22952908 suggests IL22 deficiency promotes resistance. IL22 administration in PMID:25395539 report possible viral protection.
COVID-19 research v0.144 IL22 Rebecca Foulger Gene: il22 has been classified as Red List (Low Evidence).
COVID-19 research v0.143 IL22 Rebecca Foulger commented on gene: IL22: Mouse model in PMID:22952908: Il22(-/-) mice were more resistant to lethal West Nile virus (WNV) encephalitis.
COVID-19 research v0.141 FURIN Eleanor Williams gene: FURIN was added
gene: FURIN was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: FURIN was set to Unknown
Added comment: Preprint - https://doi.org/10.1101/2020.04.18.047951- Zhong et al
Found Furin is expressed in oral mucosal cells. A Furin cutting site has been identified in SARS-CoV-2 (https://doi.org/10.1101/2020.02.10.942185 - preprint)
Sources: Literature
COVID-19 research v0.140 ACE2 Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.

Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al
Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asseleta et al
ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients.
; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.

Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al
Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asselta et al
ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients.
COVID-19 research v0.140 ACE2 Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.

Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al
Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed.
; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.

Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al
Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asseleta et al
ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients.
COVID-19 research v0.140 DMBT1 Eleanor Williams gene: DMBT1 was added
gene: DMBT1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: DMBT1 was set to Unknown
Review for gene: DMBT1 was set to RED
Added comment: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.16.045617v1 - Han et al
Found using single cell transcriptomics that DMBT1 (a viral binding scavenger) was highly expressed in alveolar type II cells relative to other lung epithelial subsets and its expression positively correlated with ACE2.
Sources: Literature
COVID-19 research v0.139 LY6E Eleanor Williams gene: LY6E was added
gene: LY6E was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: LY6E was set to Unknown
Review for gene: LY6E was set to RED
Added comment: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.02.021469v1 - Zhao et al
Found that human cell line C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2. Ectopic expression of LY6E in HEK 293 cells inhibited the entry of HCoV-OC43. Overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43 and knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. LY6E also restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2.
Sources: Literature
COVID-19 research v0.138 ACE2 Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.

Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al
Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed.
COVID-19 research v0.138 TRIB3 Eleanor Williams gene: TRIB3 was added
gene: TRIB3 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: TRIB3 was set to Unknown
Publications for gene: TRIB3 were set to 27252525; https://www.biorxiv.org/content/10.1101/2020.04.07.030767v1
Added comment: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.030767v1 - de Moraes et al
Analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. Identified TRIB3 expression was decreased in older males. Found TRIB3
expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2.

PMID: 27252525 - Tran et al 2016- Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased Hepatitis C viral replication
Sources: Literature
COVID-19 research v0.137 ACE2 Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al
Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the
virus to infect the host cell.

Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko
Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.
COVID-19 research v0.137 ACE2 Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al
Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.

Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al
Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.
COVID-19 research v0.137 ACE2 Eleanor Williams commented on gene: ACE2
COVID-19 research v0.137 ALPI Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29567797 - Parlato et al 2018- report ALPI mutations in two unrelated patients with severe intestinal inflammation and autoimmunity. WES was used. Patient 1 - non‐consanguineous parents. At 2 years old was diagnosed with coeliac disease from HLA-typing. At age 3 had recurrent abdominal pain, rectal bleeding and severe diarrhoea. Patient 2 - non‐consanguineous parents of Jewish Ashkenazi origin. Age 15 he was diagnosed with ileocolonic Crohn's disease. Compound heterozygous mutations in the ALPI gene were found in both patients. Three variants result in the substitution of residues highly conserved across species (A97T, A350V and A360) and one variant (Q439X) introducing a premature stop codon. Functional studies in HEK293T cells showed that all ALPI mutations were loss of function. ALPI expression was reduced in patients’ biopsies.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29567797 - Parlato et al 2018- report ALPI mutations in two unrelated patients with severe intestinal inflammation and autoimmunity. WES was used. Patient 1 - non‐consanguineous parents. At 2 years old was diagnosed with coeliac disease from HLA-typing. At age 3 had recurrent abdominal pain, rectal bleeding and severe diarrhoea. Patient 2 - non‐consanguineous parents of Jewish Ashkenazi origin. Age 15 he was diagnosed with ileocolonic Crohn's disease. Compound heterozygous mutations in the ALPI gene were found in both patients. Three variants result in the substitution of residues highly conserved across species (A97T, A350V and A360) and one variant (Q439X) introducing a premature stop codon. Functional studies in HEK293T cells showed that all ALPI mutations were loss of function. ALPI expression was reduced in patients’ biopsies.

Rated Amber by Zornitza Stark on the PID panel.
COVID-19 research v0.137 ALPI Eleanor Williams commented on gene: ALPI
COVID-19 research v0.137 ADAM17 Eleanor Williams reviewed gene: ADAM17: Rating: ; Mode of pathogenicity: None; Publications: 22010916, 26683521, 25804906, 29560122; Phenotypes: ?Inflammatory skin and bowel disease, neonatal, 1 #614328; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.137 HLA-DRB1 Catherine Snow Classified gene: HLA-DRB1 as Green List (high evidence)
COVID-19 research v0.137 HLA-DRB1 Catherine Snow Added comment: Comment on list classification: Rating as Green due to expert review and publications associated with HLA-DRB1 and viral susceptibility
COVID-19 research v0.137 HLA-DRB1 Catherine Snow Gene: hla-drb1 has been classified as Green List (High Evidence).
COVID-19 research v0.136 FPR2 Catherine Snow Classified gene: FPR2 as Green List (high evidence)
COVID-19 research v0.136 FPR2 Catherine Snow Added comment: Comment on list classification: Upgrading to Green based on expert review
COVID-19 research v0.136 FPR2 Catherine Snow Gene: fpr2 has been classified as Green List (High Evidence).
COVID-19 research v0.135 MPO Catherine Snow changed review comment from: Comment on list classification: Based on an external review detailing a number of publications where MPO is reviewed because of its association in the regulation of (neutrophil extracellular traps) NET formation upgrading from Amber to Green; to: Comment on list classification: Based on an external review detailing a number of publications where MPO is reviewed because of its association in the regulation of (neutrophil extracellular traps) NET formation upgrading from Amber to Green

Should also be noted that elevated levels of inflammatory mediators (including IL-6, IL-8, and MPO) in the airway of chronic/extended or recurrent RSV infection are associated with faster lung function decline in COPD patients. PMID: 32227102
COVID-19 research v0.135 MPO Catherine Snow Publications for gene: MPO were set to 9354683; 15108282; 9637725; 32082301; 27574522; 21703402; 29325098; 29769163; 24968347
COVID-19 research v0.134 MPO Catherine Snow Classified gene: MPO as Green List (high evidence)
COVID-19 research v0.134 MPO Catherine Snow Added comment: Comment on list classification: Based on an external review detailing a number of publications where MPO is reviewed because of its association in the regulation of (neutrophil extracellular traps) NET formation upgrading from Amber to Green
COVID-19 research v0.134 MPO Catherine Snow Gene: mpo has been classified as Green List (High Evidence).
COVID-19 research v0.133 MPO Catherine Snow Publications for gene: MPO were set to 9354683; 15108282; 9637725; 32082301; 27574522; 21703402; 29325098; 29769163; 24968347
COVID-19 research v0.132 MPO Catherine Snow Publications for gene: MPO were set to 9354683; 15108282; 9637725; 32082301
COVID-19 research v0.131 AKT1 Sarah Leigh Added comment: Comment on phenotypes: OMIM cites a general phenotypic description for Cowden syndrome 1 (158350) includes Immunodeficiency in some patients (PMID 26246517).
COVID-19 research v0.131 AKT1 Sarah Leigh Phenotypes for gene: AKT1 were changed from to Cowden syndrome 6 615109
COVID-19 research v0.130 AKT1 Sarah Leigh Publications for gene: AKT1 were set to 17931677
COVID-19 research v0.129 AKT1 Sarah Leigh Publications for gene: AKT1 were set to
COVID-19 research v0.128 AKT1 Sarah Leigh Classified gene: AKT1 as Red List (low evidence)
COVID-19 research v0.128 AKT1 Sarah Leigh Added comment: Comment on list classification: AKT1 gene product can inhibit apoptosis through phosphorylation,
and the inhibition of pro-apoptotic mediators to contribute to the maintenance of the virus latent state and may facilitate transformation of human lymphotropic virus type 1 infected cells (PMID 17931677).
COVID-19 research v0.128 AKT1 Sarah Leigh Gene: akt1 has been classified as Red List (Low Evidence).
COVID-19 research v0.127 NOS2 Ivone Leong Classified gene: NOS2 as Green List (high evidence)
COVID-19 research v0.127 NOS2 Ivone Leong Gene: nos2 has been classified as Green List (High Evidence).
COVID-19 research v0.126 NOS2 Ivone Leong gene: NOS2 was added
gene: NOS2 was added to Viral susceptibility. Sources: Expert list
Mode of inheritance for gene: NOS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOS2 were set to 31995689; 11207313
Review for gene: NOS2 was set to GREEN
Added comment: NOS2 is part of the list of genes that confer susceptibility to viral infections on the COVID Human Genetic Effort website (https://www.covidhge.com/).

PMID: 31995689 describes a 51 year old man from Iran who had an acute cytomegalovirus (CMV) infection which progressed to CMV disease and later died from it. The researchers found a homozygous variant that causes a frameshift mutation in NOS2 that caused NOS2 deficiency, which might cause the patient to be more susceptible to lethal CMV infection. It is rare for CMV to cause fatality in healthy people; however, Nos2 knockout mice are susceptible to lethal infection with murine CMV (PMID: 11207313).

Based on the above evidence NOS2 has been given Green gene status.
Sources: Expert list
COVID-19 research v0.125 ACKR1 Sarah Leigh Classified gene: ACKR1 as Red List (low evidence)
COVID-19 research v0.125 ACKR1 Sarah Leigh Added comment: Comment on list classification: PMID 19180233 noted the clinical significance of the lower neutrophil counts in individuals homozygous for the Duffy-null variant in medical decision making, as white blood cell count is a marker of immunocompetence, infection, and inflammation, and they proposed the potential utility of rs2814778 genotyping. PMID 18621010, showed that rs2814778 -46CC was greater in HIV-positive patients, and -46CC individuals had a 50% higher risk of acquiring HIV, however, -46CC was associated with slower disease progression in terms of death or development of dementia. Survival appeared to be dependent on the level of WBC (PMID 19620399).
COVID-19 research v0.125 ACKR1 Sarah Leigh Gene: ackr1 has been classified as Red List (Low Evidence).
COVID-19 research v0.124 ACKR1 Sarah Leigh Publications for gene: ACKR1 were set to
COVID-19 research v0.123 ACKR1 Sarah Leigh Phenotypes for gene: ACKR1 were changed from to [Blood group, Duffy system] 110700
COVID-19 research v0.122 ACKR1 Sarah Leigh Mode of inheritance for gene: ACKR1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.121 TP53 Sarah Leigh Source OMIM was added to TP53.
COVID-19 research v0.121 TNF Sarah Leigh gene: TNF was added
gene: TNF was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: TNF was set to
COVID-19 research v0.121 TLR2 Sarah Leigh gene: TLR2 was added
gene: TLR2 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: TLR2 was set to
COVID-19 research v0.121 SERPINA1 Sarah Leigh gene: SERPINA1 was added
gene: SERPINA1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: SERPINA1 was set to
COVID-19 research v0.121 SCN5A Sarah Leigh gene: SCN5A was added
gene: SCN5A was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: SCN5A was set to
COVID-19 research v0.121 RB1 Sarah Leigh gene: RB1 was added
gene: RB1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: RB1 was set to
COVID-19 research v0.121 PDCD1 Sarah Leigh gene: PDCD1 was added
gene: PDCD1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: PDCD1 was set to
COVID-19 research v0.121 NUP214 Sarah Leigh gene: NUP214 was added
gene: NUP214 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: NUP214 was set to
COVID-19 research v0.121 MET Sarah Leigh gene: MET was added
gene: MET was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: MET was set to
COVID-19 research v0.121 LDLR Sarah Leigh gene: LDLR was added
gene: LDLR was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: LDLR was set to
COVID-19 research v0.121 KRT18 Sarah Leigh gene: KRT18 was added
gene: KRT18 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: KRT18 was set to
COVID-19 research v0.121 IRGM Sarah Leigh gene: IRGM was added
gene: IRGM was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: IRGM was set to
COVID-19 research v0.121 IL6 Sarah Leigh gene: IL6 was added
gene: IL6 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: IL6 was set to
COVID-19 research v0.121 IL4R Sarah Leigh gene: IL4R was added
gene: IL4R was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: IL4R was set to
COVID-19 research v0.121 IFNG Sarah Leigh gene: IFNG was added
gene: IFNG was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: IFNG was set to
COVID-19 research v0.121 IFITM3 Sarah Leigh gene: IFITM3 was added
gene: IFITM3 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: IFITM3 was set to
COVID-19 research v0.121 ICAM1 Sarah Leigh gene: ICAM1 was added
gene: ICAM1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: ICAM1 was set to
COVID-19 research v0.121 HTR2A Sarah Leigh gene: HTR2A was added
gene: HTR2A was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: HTR2A was set to
COVID-19 research v0.121 HLA-DQB1 Sarah Leigh gene: HLA-DQB1 was added
gene: HLA-DQB1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: HLA-DQB1 was set to
COVID-19 research v0.121 HLA-C Sarah Leigh gene: HLA-C was added
gene: HLA-C was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: HLA-C was set to
COVID-19 research v0.121 HFE Sarah Leigh gene: HFE was added
gene: HFE was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: HFE was set to
COVID-19 research v0.121 HBB Sarah Leigh gene: HBB was added
gene: HBB was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: HBB was set to
COVID-19 research v0.121 DMD Sarah Leigh gene: DMD was added
gene: DMD was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: DMD was set to
COVID-19 research v0.121 CYP2B6 Sarah Leigh gene: CYP2B6 was added
gene: CYP2B6 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CYP2B6 was set to
COVID-19 research v0.121 CX3CR1 Sarah Leigh gene: CX3CR1 was added
gene: CX3CR1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CX3CR1 was set to
COVID-19 research v0.121 CR1 Sarah Leigh gene: CR1 was added
gene: CR1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CR1 was set to
COVID-19 research v0.121 CPT2 Sarah Leigh gene: CPT2 was added
gene: CPT2 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CPT2 was set to
COVID-19 research v0.121 CIB1 Sarah Leigh Source OMIM was added to CIB1.
COVID-19 research v0.121 CD209 Sarah Leigh gene: CD209 was added
gene: CD209 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CD209 was set to
COVID-19 research v0.121 CCR5 Sarah Leigh gene: CCR5 was added
gene: CCR5 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CCR5 was set to
COVID-19 research v0.121 CCND1 Sarah Leigh gene: CCND1 was added
gene: CCND1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CCND1 was set to
COVID-19 research v0.121 CCL3L1 Sarah Leigh gene: CCL3L1 was added
gene: CCL3L1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CCL3L1 was set to
COVID-19 research v0.121 CCL11 Sarah Leigh gene: CCL11 was added
gene: CCL11 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: CCL11 was set to
COVID-19 research v0.121 AKT1 Sarah Leigh gene: AKT1 was added
gene: AKT1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: AKT1 was set to
COVID-19 research v0.121 ACKR1 Sarah Leigh gene: ACKR1 was added
gene: ACKR1 was added to Viral susceptibility. Sources: OMIM
Mode of inheritance for gene: ACKR1 was set to
COVID-19 research v0.120 HLA-B Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Red to Green. Although not all studies agree on the association of specific HLA-B alleles and SARS infection (e.g. PMIDs 12969506, 15243926), these studies do both report an association. PMID:18186801 do not report an association between tested HLA-B alleles and SARS development but on balance in-silico evidence also suggests that HLA-B alleles could play a role in modifying the response to the virus. Therefore Green rating is appropriate for this research panel.; to: Comment on list classification: Updated rating from Red to Green. Although not all studies agree on the association of specific HLA-B alleles and SARS infection (e.g. PMIDs 12969506, 15243926), these studies do both report an association. PMID:18186801 do not report an association between tested HLA-B alleles and SARS development, but on balance in-silico evidence also suggests that HLA-B alleles could play a role in modifying the response to the virus. Therefore Green rating is appropriate for this research panel.
COVID-19 research v0.120 HLA-B Rebecca Foulger Classified gene: HLA-B as Green List (high evidence)
COVID-19 research v0.120 HLA-B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green. Although not all studies agree on the association of specific HLA-B alleles and SARS infection (e.g. PMIDs 12969506, 15243926), these studies do both report an association. PMID:18186801 do not report an association between tested HLA-B alleles and SARS development but on balance in-silico evidence also suggests that HLA-B alleles could play a role in modifying the response to the virus. Therefore Green rating is appropriate for this research panel.
COVID-19 research v0.120 HLA-B Rebecca Foulger Gene: hla-b has been classified as Green List (High Evidence).
COVID-19 research v0.119 HLA-B Rebecca Foulger commented on gene: HLA-B: PMID:15839463 (Umapathy et al., 2004). Full text is unavailable. Title: Absence of HLA B*46 in Indian population: could it be the cause for protection from SARS epidemic?
COVID-19 research v0.119 HLA-B Rebecca Foulger commented on gene: HLA-B: PMID:18540051 (Roder et al., 2008 examine the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) (full text unavailable at time of curation).
COVID-19 research v0.119 HLA-B Rebecca Foulger commented on gene: HLA-B: PMID:32303592 (Nguyen et al., 2020) performed in-silico analysis of viral-binding affinity across HLA genotypes for SARS-CoV-2 peptides. Based on in-silico results, they suggest that individuals with HLA-B*46:01 may be vulnerable to COVID-19. Conversely, HLA-B*15:03 may enable greater immunity.
COVID-19 research v0.119 HLA-B Rebecca Foulger Publications for gene: HLA-B were set to 12969506; 15243926; 18186801
COVID-19 research v0.118 HLA-B Rebecca Foulger commented on gene: HLA-B
COVID-19 research v0.118 IL18 Rebecca Foulger changed review comment from: PMID:25395539 (Zhang et al 2014) report that IL-18 and IL-22 administration to mice offered protection against a broad range of RV inoculation, and may offer broad antibiral therapeutic potential.; to: PMID:25395539 (Zhang et al 2014) report that IL-18 and IL-22 administration to mice offered protection against a broad range of RV inoculation, and may offer broad antiviral therapeutic potential.
COVID-19 research v0.118 IL22 Rebecca Foulger changed review comment from: PMID:25395539 (Zhang et al 2014) report that IL-18 and IL-22 administration to mice offered protection against a broad range of RV inoculation, and may offer broad antibiral therapeutic potential.; to: PMID:25395539 (Zhang et al 2014) report that IL-18 and IL-22 administration to mice offered protection against a broad range of RV inoculation, and may offer broad antiviral therapeutic potential.
COVID-19 research v0.118 IL22 Rebecca Foulger Publications for gene: IL22 were set to 25395539
COVID-19 research v0.117 IL22 Rebecca Foulger Publications for gene: IL22 were set to
COVID-19 research v0.116 IL22 Rebecca Foulger commented on gene: IL22
COVID-19 research v0.116 IL18 Rebecca Foulger Classified gene: IL18 as Amber List (moderate evidence)
COVID-19 research v0.116 IL18 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber, based largely on PMID:31660404 who report identification of IL-18 polymorphisms that may confer a higher incidence of CMV infection (in kidney transplant patients). Additional expression assays studies in mice support a role for IL-18 in innate immunity viral response.
COVID-19 research v0.116 IL18 Rebecca Foulger Gene: il18 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.115 IL18 Rebecca Foulger commented on gene: IL18: PMID:31660404. Perez-Flores examines two SNPs in the promoter region of IL-18 gene (-607C/A (rs1946518) and -137G/C (rs187238) in 498 adult kidney transplant recipients. Results suggest that the rs1946518/rs187238 haplotype is associated with a higher incidence of post-prophylaxis cytomegalovirus (CMV) infection. Prior identification of these SNPs could help select alternative measures to prevent delayed-onset CMV infection in these patients.
COVID-19 research v0.115 IL18 Rebecca Foulger Publications for gene: IL18 were set to 15606801; 25395539
COVID-19 research v0.114 IL18 Rebecca Foulger Publications for gene: IL18 were set to 15606801
COVID-19 research v0.113 IL18 Rebecca Foulger commented on gene: IL18: PMID:25395539 (Zhang et al 2014) report that IL-18 and IL-22 administration to mice offered protection against a broad range of RV inoculation, and may offer broad antibiral therapeutic potential.
COVID-19 research v0.113 IL18 Rebecca Foulger changed review comment from: PMID:15606801 (Van Der Sluijs et al., 2005): IL18 is upregulated in after Influenza infection, and IL18 deficiency is associated with accelerated viral clearance.; to: PMID:15606801 (Van Der Sluijs et al., 2005): IL18 is upregulated in after Influenza infection, and IL18 deficiency is associated with accelerated viral clearance (mouse study).
COVID-19 research v0.113 IL18 Rebecca Foulger Publications for gene: IL18 were set to 15606801
COVID-19 research v0.112 IL18 Rebecca Foulger Publications for gene: IL18 were set to
COVID-19 research v0.111 IL18 Rebecca Foulger commented on gene: IL18
COVID-19 research v0.111 TMPRSS2 Catherine Snow changed review comment from: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2.

This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878
Sources: Literature; to: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2. Papers identified include:
PMID: 25904605 which reported that higher TMPRSS2 expression variant, rs2070788 GG genotype, was associated with higher susceptibility to severe illness in patients with A(H1N1)pdm09 influenza.
PMID: 24600012 showed that TMPRSS2 is the key host protease that activates IAVs in vivo through proteolytic cleavage of their HA proteins
PMID: 24522916 looked at knockout mice that do not express TMPRSS2 that are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection

This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878
Sources: Literature
COVID-19 research v0.111 TMPRSS2 Catherine Snow Classified gene: TMPRSS2 as Amber List (moderate evidence)
COVID-19 research v0.111 TMPRSS2 Catherine Snow Gene: tmprss2 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.110 TMPRSS2 Catherine Snow gene: TMPRSS2 was added
gene: TMPRSS2 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: TMPRSS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMPRSS2 were set to 31488196
Review for gene: TMPRSS2 was set to AMBER
Added comment: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2.

This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878
Sources: Literature
COVID-19 research v0.109 PARP1 Sarah Leigh changed review comment from: PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor. Therefore, activiation of PARP1 could promote Influenza infection.
Sources: Literature; to: PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor. Therefore, activiation of PARP1 could promote Influenza infection, by interfering with the IFNAR1.
Sources: Literature
COVID-19 research v0.109 PARP1 Sarah Leigh gene: PARP1 was added
gene: PARP1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: PARP1 was set to Unknown
Publications for gene: PARP1 were set to 31915279
Added comment: PARP1 Enhances Influenza A Virus Propagation by Facilitating Degradation of Host Type I Interferon Receptor. Therefore, activiation of PARP1 could promote Influenza infection.
Sources: Literature
COVID-19 research v0.108 RECQL4 Sarah Leigh Classified gene: RECQL4 as Green List (high evidence)
COVID-19 research v0.108 RECQL4 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 3 unrelated cases in which immunodeficiecy was a feature (PMID 16630167; 21143835; 26064716). In addition RECQL4 variants have been implicated in Acrodermatitis Enteropathica caused by SLC39A4 (p.Gly512Trp)(PMID 30174688)
COVID-19 research v0.108 RECQL4 Sarah Leigh Gene: recql4 has been classified as Green List (High Evidence).
COVID-19 research v0.107 RECQL4 Sarah Leigh Publications for gene: RECQL4 were set to 16630167
COVID-19 research v0.106 ELF4 Rebecca Foulger commented on gene: ELF4: Some evidence that ELF4 is involved in the anti-viral innate immune response, but no genetic data. Therefore keeping rating as Red.
COVID-19 research v0.106 ELF4 Rebecca Foulger changed review comment from: PMID:30089112 (Du et al., 2018) show that during the antiviral response, miR-221 was induced through ELF4 binding to its promoter.; to: PMID:30089112 (Du et al., 2018) show that during the antiviral response, miR-221 was induced through ELF4 binding to its promoter (mice cells, recombinant human ELF4).
COVID-19 research v0.106 ELF4 Rebecca Foulger commented on gene: ELF4: PMID:30089112 (Du et al., 2018) show that during the antiviral response, miR-221 was induced through ELF4 binding to its promoter.
COVID-19 research v0.106 ELF4 Rebecca Foulger commented on gene: ELF4
COVID-19 research v0.106 COLEC11 Rebecca Foulger commented on gene: COLEC11
COVID-19 research v0.106 CNBP Rebecca Foulger commented on gene: CNBP
COVID-19 research v0.106 POLR3F Ivone Leong Publications for gene: POLR3F were set to 30211253
COVID-19 research v0.105 POLR3C Ivone Leong Publications for gene: POLR3C were set to 28783042
COVID-19 research v0.104 POLR3A Ivone Leong Publications for gene: POLR3A were set to 29728610; 28783042
COVID-19 research v0.103 OAS1 Ivone Leong reviewed gene: OAS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.103 IKZF1 Ivone Leong reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
COVID-19 research v0.103 TMEM173 Ivone Leong reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 TCF3 Ivone Leong reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 STXBP2 Ivone Leong reviewed gene: STXBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 STAT5B Ivone Leong reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 RANBP2 Ivone Leong reviewed gene: RANBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 PSMB8 Ivone Leong reviewed gene: PSMB8: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 PIK3CD Ivone Leong reviewed gene: PIK3CD: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 JAK1 Ivone Leong reviewed gene: JAK1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 FOXN1 Ivone Leong reviewed gene: FOXN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 C3 Ivone Leong reviewed gene: C3: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 C1S Ivone Leong reviewed gene: C1S: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 C1R Ivone Leong reviewed gene: C1R: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 AICDA Ivone Leong reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.103 TP53 Ivone Leong reviewed gene: TP53: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Bone marrow failure syndrome 5, 618165; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 SRP72 Ivone Leong reviewed gene: SRP72: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Bone marrow failure syndrome 1, 614675; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 RFWD3 Ivone Leong reviewed gene: RFWD3: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ?Fanconi anemia, complementation group W, 617784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 MAD2L2 Ivone Leong reviewed gene: MAD2L2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ?Fanconi anemia, complementation group V, 617243 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 XRCC2 Ivone Leong reviewed gene: XRCC2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ?Fanconi anemia, complementation group U, 617247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 UBE2T Ivone Leong reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group T, 616435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 RAD51 Ivone Leong reviewed gene: RAD51: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: ?Fanconi anemia, complementation group R, 617244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 SLX4 Ivone Leong reviewed gene: SLX4: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group P, 613951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 RAD51C Ivone Leong reviewed gene: RAD51C: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group O, 613390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 PALB2 Ivone Leong reviewed gene: PALB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group N, 610832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCL Ivone Leong reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group L, 614083; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 BRIP1 Ivone Leong reviewed gene: BRIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group J, 609054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCG Ivone Leong reviewed gene: FANCG: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group G, 614082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCE Ivone Leong reviewed gene: FANCE: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group E, 600901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCD2 Ivone Leong reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group D2, 227646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCC Ivone Leong reviewed gene: FANCC: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group C, 227645; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 FANCB Ivone Leong reviewed gene: FANCB: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group B, 300514; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
COVID-19 research v0.103 FANCA Ivone Leong reviewed gene: FANCA: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Fanconi anemia, complementation group A, 227650 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 IL18BP Ivone Leong reviewed gene: IL18BP: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, inborn errors of immunity related to leukocytes, IL-18BP deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 IRF4 Ivone Leong reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, inborn errors of immunity related to leukocytes, IRF4 haploinsufficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 POLR3F Ivone Leong reviewed gene: POLR3F: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Predisposition to severe viral infection, RNA polymerase III deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 POLR3C Ivone Leong reviewed gene: POLR3C: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Predisposition to severe viral infection, RNA polymerase III deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 POLR3A Ivone Leong reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Predisposition to severe viral infection, RNA polymerase III deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.103 CIB1 Ivone Leong reviewed gene: CIB1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Epidermodysplasia verruciformis, CIB1 deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 IL23R Ivone Leong reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Mendelian susceptibility to mycobacterial disease, IL-23R deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 IL12RB2 Ivone Leong reviewed gene: IL12RB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Defects in intrinsic and innate immunity, Mendelian susceptibility to mycobacterial disease, IL-12Rb2 deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.103 EFL1 Ivone Leong reviewed gene: EFL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32086639, 32048120; Phenotypes: Congenital defects of phagocyte number or function, Congenital neutropenias, Shwachman-Diamond Syndrome, 617941; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
COVID-19 research v0.102 TMEM173 Ivone Leong Source IUIS Classification December 2032 was added to TMEM173.
Mode of inheritance for gene TMEM173 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 TCF3 Ivone Leong Source IUIS Classification December 2031 was added to TCF3.
Mode of inheritance for gene TCF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 STXBP2 Ivone Leong Source IUIS Classification December 2030 was added to STXBP2.
Mode of inheritance for gene STXBP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 STAT5B Ivone Leong Source IUIS Classification December 2029 was added to STAT5B.
Mode of inheritance for gene STAT5B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 RANBP2 Ivone Leong Source IUIS Classification December 2028 was added to RANBP2.
Mode of inheritance for gene RANBP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 PSMB8 Ivone Leong Source IUIS Classification December 2027 was added to PSMB8.
Mode of inheritance for gene PSMB8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 PIK3CD Ivone Leong Source IUIS Classification December 2026 was added to PIK3CD.
Mode of inheritance for gene PIK3CD was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 JAK1 Ivone Leong Source IUIS Classification December 2025 was added to JAK1.
Mode of inheritance for gene JAK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 FOXN1 Ivone Leong Source IUIS Classification December 2024 was added to FOXN1.
Mode of inheritance for gene FOXN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 C3 Ivone Leong Source IUIS Classification December 2022 was added to C3.
Mode of inheritance for gene C3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 C1S Ivone Leong Source IUIS Classification December 2021 was added to C1S.
Mode of inheritance for gene C1S was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 C1R Ivone Leong Source IUIS Classification December 2020 was added to C1R.
Mode of inheritance for gene C1R was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 AICDA Ivone Leong Source IUIS Classification December 2019 was added to AICDA.
Mode of inheritance for gene AICDA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.102 TP53 Ivone Leong gene: TP53 was added
gene: TP53 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TP53 were set to 32086639; 32048120
Phenotypes for gene: TP53 were set to Bone marrow failure syndrome 5, 618165
COVID-19 research v0.102 SRP72 Ivone Leong gene: SRP72 was added
gene: SRP72 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: SRP72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRP72 were set to 32086639; 32048120
Phenotypes for gene: SRP72 were set to Bone marrow failure syndrome 1, 614675
COVID-19 research v0.102 RFWD3 Ivone Leong gene: RFWD3 was added
gene: RFWD3 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: RFWD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFWD3 were set to 32086639; 32048120
Phenotypes for gene: RFWD3 were set to ?Fanconi anemia, complementation group W, 617784
COVID-19 research v0.102 MAD2L2 Ivone Leong gene: MAD2L2 was added
gene: MAD2L2 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAD2L2 were set to 32086639; 32048120
Phenotypes for gene: MAD2L2 were set to ?Fanconi anemia, complementation group V, 617243
COVID-19 research v0.102 XRCC2 Ivone Leong gene: XRCC2 was added
gene: XRCC2 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: XRCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC2 were set to 32086639; 32048120
Phenotypes for gene: XRCC2 were set to ?Fanconi anemia, complementation group U, 617247
COVID-19 research v0.102 UBE2T Ivone Leong gene: UBE2T was added
gene: UBE2T was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE2T were set to 32086639; 32048120
Phenotypes for gene: UBE2T were set to Fanconi anemia, complementation group T, 616435
COVID-19 research v0.102 RAD51 Ivone Leong gene: RAD51 was added
gene: RAD51 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: RAD51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51 were set to 32086639; 32048120
Phenotypes for gene: RAD51 were set to ?Fanconi anemia, complementation group R, 617244
COVID-19 research v0.102 SLX4 Ivone Leong gene: SLX4 was added
gene: SLX4 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLX4 were set to 32086639; 32048120
Phenotypes for gene: SLX4 were set to Fanconi anemia, complementation group P, 613951
COVID-19 research v0.102 RAD51C Ivone Leong gene: RAD51C was added
gene: RAD51C was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: RAD51C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51C were set to 32086639; 32048120
Phenotypes for gene: RAD51C were set to Fanconi anemia, complementation group O, 613390
COVID-19 research v0.102 PALB2 Ivone Leong gene: PALB2 was added
gene: PALB2 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALB2 were set to 32086639; 32048120
Phenotypes for gene: PALB2 were set to Fanconi anemia, complementation group N, 610832
COVID-19 research v0.102 FANCL Ivone Leong gene: FANCL was added
gene: FANCL was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCL were set to 32086639; 32048120
Phenotypes for gene: FANCL were set to Fanconi anemia, complementation group L, 614083
COVID-19 research v0.102 BRIP1 Ivone Leong gene: BRIP1 was added
gene: BRIP1 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRIP1 were set to 32086639; 32048120
Phenotypes for gene: BRIP1 were set to Fanconi anemia, complementation group J, 609054
COVID-19 research v0.102 FANCG Ivone Leong gene: FANCG was added
gene: FANCG was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCG were set to 32086639; 32048120
Phenotypes for gene: FANCG were set to Fanconi anemia, complementation group G, 614082
COVID-19 research v0.102 FANCE Ivone Leong gene: FANCE was added
gene: FANCE was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCE were set to 32086639; 32048120
Phenotypes for gene: FANCE were set to Fanconi anemia, complementation group E, 600901
COVID-19 research v0.102 FANCD2 Ivone Leong gene: FANCD2 was added
gene: FANCD2 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCD2 were set to 32086639; 32048120
Phenotypes for gene: FANCD2 were set to Fanconi anemia, complementation group D2, 227646
COVID-19 research v0.102 FANCC Ivone Leong gene: FANCC was added
gene: FANCC was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCC were set to 32086639; 32048120
Phenotypes for gene: FANCC were set to Fanconi anemia, complementation group C, 227645
COVID-19 research v0.102 FANCB Ivone Leong gene: FANCB was added
gene: FANCB was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FANCB were set to 32086639; 32048120
Phenotypes for gene: FANCB were set to Fanconi anemia, complementation group B, 300514
COVID-19 research v0.102 FANCA Ivone Leong gene: FANCA was added
gene: FANCA was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCA were set to 32086639; 32048120
Phenotypes for gene: FANCA were set to Fanconi anemia, complementation group A, 227650
COVID-19 research v0.102 IL18BP Ivone Leong Source Expert Review Green was added to IL18BP.
Source IUIS Classification December 2019 was added to IL18BP.
Mode of inheritance for gene IL18BP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Defects in intrinsic and innate immunity; IL-18BP deficiency; inborn errors of immunity related to leukocytes for gene: IL18BP
Publications for gene IL18BP were updated from PubMed: 31213488 to 32086639; 32048120; PubMed: 31213488
Rating Changed from No List (delete) to Green List (high evidence)
COVID-19 research v0.102 IRF4 Ivone Leong gene: IRF4 was added
gene: IRF4 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: IRF4 was set to
Phenotypes for gene: IRF4 were set to Defects in intrinsic and innate immunity; IRF4 haploinsufficiency; inborn errors of immunity related to leukocytes
COVID-19 research v0.102 POLR3F Ivone Leong Source Expert Review Green was added to POLR3F.
Source IUIS Classification December 2019 was added to POLR3F.
Added phenotypes RNA polymerase III deficiency; Defects in intrinsic and innate immunity; Predisposition to severe viral infection for gene: POLR3F
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.102 POLR3C Ivone Leong Source Expert Review Green was added to POLR3C.
Source IUIS Classification December 2019 was added to POLR3C.
Added phenotypes RNA polymerase III deficiency; Defects in intrinsic and innate immunity; Predisposition to severe viral infection for gene: POLR3C
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.102 POLR3A Ivone Leong Source Expert Review Green was added to POLR3A.
Source IUIS Classification December 2019 was added to POLR3A.
Added phenotypes RNA polymerase III deficiency; Defects in intrinsic and innate immunity; Predisposition to severe viral infection for gene: POLR3A
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.102 CIB1 Ivone Leong gene: CIB1 was added
gene: CIB1 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIB1 were set to 32086639; 32048120
Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis; Defects in intrinsic and innate immunity; CIB1 deficiency
COVID-19 research v0.102 IL23R Ivone Leong gene: IL23R was added
gene: IL23R was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: IL23R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL23R were set to 32086639; 32048120
Phenotypes for gene: IL23R were set to Defects in intrinsic and innate immunity; Mendelian susceptibility to mycobacterial disease; IL-23R deficiency
COVID-19 research v0.102 IL12RB2 Ivone Leong gene: IL12RB2 was added
gene: IL12RB2 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: IL12RB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL12RB2 were set to 32086639; 32048120
Phenotypes for gene: IL12RB2 were set to Defects in intrinsic and innate immunity; Mendelian susceptibility to mycobacterial disease; IL-12Rb2 deficiency
COVID-19 research v0.102 EFL1 Ivone Leong gene: EFL1 was added
gene: EFL1 was added to Viral susceptibility. Sources: Expert Review Green,IUIS Classification December 2019
Mode of inheritance for gene: EFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFL1 were set to 32086639; 32048120
Phenotypes for gene: EFL1 were set to Congenital neutropenias; Congenital defects of phagocyte number or function; Shwachman-Diamond Syndrome, 617941
COVID-19 research v0.101 ACE2 Rebecca Foulger commented on gene: ACE2: Added ACE2 to the panel as an Amber gene: many papers demonstrate that ACE2 acts as a cell receptor for Coronaviruses (e.g. PMIDs 32142651, 15897467, 14647384).
COVID-19 research v0.101 ACE2 Rebecca Foulger Classified gene: ACE2 as Amber List (moderate evidence)
COVID-19 research v0.101 ACE2 Rebecca Foulger Gene: ace2 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.100 ACE2 Rebecca Foulger gene: ACE2 was added
gene: ACE2 was added to Viral susceptibility. Sources: Other
Mode of inheritance for gene: ACE2 was set to Unknown
Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651
Review for gene: ACE2 was set to AMBER
Added comment: Sources: Other
COVID-19 research v0.99 CD4 Rebecca Foulger Publications for gene: CD4 were set to
COVID-19 research v0.98 CD4 Rebecca Foulger commented on gene: CD4
COVID-19 research v0.98 CD14 Rebecca Foulger Classified gene: CD14 as Amber List (moderate evidence)
COVID-19 research v0.98 CD14 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber: at least 2 publications supporting a link between CD14 polymorphism and viral infection (SARs and RSV).
COVID-19 research v0.98 CD14 Rebecca Foulger Gene: cd14 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.97 CD14 Rebecca Foulger Publications for gene: CD14 were set to 17913858
COVID-19 research v0.96 CD14 Rebecca Foulger commented on gene: CD14
COVID-19 research v0.96 ITGAM Catherine Snow Publications for gene: ITGAM were set to
COVID-19 research v0.95 ITGAM Catherine Snow Mode of inheritance for gene: ITGAM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.94 ITGAM Catherine Snow Classified gene: ITGAM as Amber List (moderate evidence)
COVID-19 research v0.94 ITGAM Catherine Snow Gene: itgam has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.93 ITGAM Catherine Snow reviewed gene: ITGAM: Rating: AMBER; Mode of pathogenicity: None; Publications: 29712964, 32257537; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.93 RC3H1 Sarah Leigh Classified gene: RC3H1 as Amber List (moderate evidence)
COVID-19 research v0.93 RC3H1 Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM (lasted edited 01/27/2017) or in Gen2Phen. PMID 31636267 reports a biallelic nonsense variant (p.R688*), in a case with immune dysregulation syndrome
characterized by severe hyperinflammation in a consanguineous family. The association of this variant with the phenotype is supported by functional studies and mouse model (PMID 15917799).
COVID-19 research v0.93 RC3H1 Sarah Leigh Gene: rc3h1 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.92 RC3H1 Sarah Leigh Publications for gene: RC3H1 were set to PMID: 31636267
COVID-19 research v0.91 CCL5 Rebecca Foulger Classified gene: CCL5 as Amber List (moderate evidence)
COVID-19 research v0.91 CCL5 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber: Some evidence that CCL5 (aka RANTES) polymorphisms may be associated with viral infections, including SARS.
COVID-19 research v0.91 CCL5 Rebecca Foulger Gene: ccl5 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.90 CCL5 Rebecca Foulger Publications for gene: CCL5 were set to 17540042; 22576913
COVID-19 research v0.89 CCL5 Rebecca Foulger commented on gene: CCL5: PMID:30175654 (El-Bendary et al., 2019) report rs3817655 polymorphism in CCL5 may be associated with spontaneous clearance of Hepatitis C virus (HCV).
COVID-19 research v0.89 CCL5 Rebecca Foulger commented on gene: CCL5: PMID:31874580 (Sheng et al. 2019) study suggests that the CCL5 rs2107538 polymorphism was correlated with TB (infectious disease caused by Mycobacterium tuberculosis) susceptibility in Caucasians. The rs2107538 polymorphism is suggested to affect CCL5 expression.
COVID-19 research v0.89 CCL5 Rebecca Foulger Publications for gene: CCL5 were set to 17540042
COVID-19 research v0.88 CCL5 Rebecca Foulger commented on gene: CCL5
COVID-19 research v0.88 CCL2 Rebecca Foulger Classified gene: CCL2 as Green List (high evidence)
COVID-19 research v0.88 CCL2 Rebecca Foulger Added comment: Comment on list classification: Updated rating of CCL2 from Red to Green. 3 publications supporting an association between CCL2 SNP(s) and viral infections including HIV, Japanese encephalitis and SARs. Additional evidence that CCL2 levels are raised after viral infection.
COVID-19 research v0.88 CCL2 Rebecca Foulger Gene: ccl2 has been classified as Green List (High Evidence).
COVID-19 research v0.87 CCL2 Rebecca Foulger Phenotypes for gene: CCL2 were changed from {HIV-1, resistance to}, 609423; Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection; Susceptibility to SARS-CoV to {HIV-1, resistance to}, 609423; Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection; Susceptibility to SARS-CoV; Susceptibility to viral Japanese encephalitis
COVID-19 research v0.86 CCL2 Rebecca Foulger Publications for gene: CCL2 were set to 25818534; 26687605; 16916890; 24788844; 27260136
COVID-19 research v0.85 CCL2 Rebecca Foulger commented on gene: CCL2: PMID:29057937 (Chowdhury and Khan, 2017) report that SNPs of CCL2 (rs1024611G) and its receptor CCR2 (rs1799864A) significantly associated with Japanese encephalitis (JE) which may serve as possible genetic predisposing factor. JE is one of the major viral encephalitis in Asia and parts of Western Pacific.
COVID-19 research v0.85 PSMB10 Sarah Leigh Classified gene: PSMB10 as Amber List (moderate evidence)
COVID-19 research v0.85 PSMB10 Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM (last edited on 06/25/2007) or in Gen2Phen. PMID 31783057 reports a case of Proteasome-associated autoinflammatory syndrome in an infant with a biallelic variant (c.41T>C, p.Phe14Ser), together with supporting functional studies.
COVID-19 research v0.85 PSMB10 Sarah Leigh Gene: psmb10 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.84 PSMB10 Sarah Leigh Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome to Proteasome-associated autoinflammatory syndrome (PRAAS)
COVID-19 research v0.83 NFKBID Sarah Leigh Classified gene: NFKBID as Red List (low evidence)
COVID-19 research v0.83 NFKBID Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. The only variants are structural rearrangements that include NFKBID amongst other genes. PMID 26973645 reports "heterozygous mutation in the nfkbid gene encoding the atypical IκB protein IκBNS led to reduced steady state IgM and IgG3 antibody levels and impaired response to vaccination with TI-2 antigens in mice". Thus, variants in human NFKBID may also result in reduced levels of IgM and IgG3 and compromized vaccination responses.
COVID-19 research v0.83 NFKBID Sarah Leigh Gene: nfkbid has been classified as Red List (Low Evidence).
COVID-19 research v0.82 NFKBID Sarah Leigh Publications for gene: NFKBID were set to
COVID-19 research v0.81 SART3 Catherine Snow reviewed gene: SART3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 IL18BP Abdelazeem Elhabyan gene: IL18BP was added
gene: IL18BP was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: IL18BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL18BP were set to PubMed: 31213488
Mode of pathogenicity for gene: IL18BP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Inherited IL-18BP deficiency in human fulminant viral hepatitis

Fulminant viral hepatitis (FVH) is a devastating and unexplained condition that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. We report a child who died of FVH upon infection with hepatitis A virus (HAV) at age 11 yr and who was homozygous for a private 40-nucleotide deletion in IL18BP, which encodes the IL-18 binding protein (IL-18BP). This mutation is loss-of-function, unlike the variants found in a homozygous state in public databases. We show that human IL-18 and IL-18BP are both secreted mostly by hepatocytes and macrophages in the liver. Moreover, in the absence of IL-18BP, excessive NK cell activation by IL-18 results in the uncontrolled killing of human hepatocytes in vitro. Inherited human IL-18BP deficiency thus underlies fulminant HAV hepatitis by unleashing IL-18. These findings provide proof-of-principle that FVH can be caused by single-gene inborn errors that selectively disrupt liver-specific immunity. They also show that human IL-18 is toxic to the liver and that IL-18BP is its antidote.
Sources: Literature
COVID-19 research v0.81 HLA-DRB1 Abdelazeem Elhabyan gene: HLA-DRB1 was added
gene: HLA-DRB1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: HLA-DRB1 was set to Unknown
Publications for gene: HLA-DRB1 were set to PMID: 19445991,26456283,19597844,10823757,
Penetrance for gene: HLA-DRB1 were set to unknown
Mode of pathogenicity for gene: HLA-DRB1 was set to Other
Review for gene: HLA-DRB1 was set to GREEN
Added comment: Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population PMID: 19445991,

HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses PMID: 26456283
The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation

Clear and Independent Associations of Several HLA-DRB1 Alleles With Differential Antibody Responses to Hepatitis B Vaccination in Youth
PMID: 19597844
To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(-)) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration > or = 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008).

Influence of HLA Supertypes on Susceptibility and Resistance to Human Immunodeficiency Virus Type 1 Infection
PMID: 10823757
To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge
Sources: Literature
COVID-19 research v0.81 PSMB4 Abdelazeem Elhabyan reviewed gene: PSMB4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26829627,; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 POLR3C Abdelazeem Elhabyan reviewed gene: POLR3C: Rating: RED; Mode of pathogenicity: None; Publications: 28783042; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 POLR3A Abdelazeem Elhabyan changed review comment from: This gene is responsible for A subunit of Polymerase which sense DNA in viral infection eg Varicella Zoster. SARS-CoV-2 is an RNA virus.

Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections(PMID: 28783042)

We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). POLR3A and POLR3C encode subunits of RNA polymerase III. Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA. Moreover, leukocytes from 3 of the patients displayed defective IFN production upon VZV infection and reduced control of VZV replication. These phenotypes were rescued by transduction with relevant WT alleles. This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity
Different classes of PRRs are involved in recognition of virus infections, including membrane-associated TLRs; cytosolic retinoic acid–inducible gene 1–like (RIG-I–like) receptors, which sense RNA; and DNA sensors (24). Each of these classes of PRRs stimulates production of IFNs, which exhibit antiviral activity through their ability to induce IFN-stimulated genes (ISGs). With respect to DNA sensors, TLR9 detects unmethylated DNA, RNA polymerase III (POL III) recognizes AT-rich DNA, while gamma-interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) sense double-stranded DNA in a sequence-independent manner (25–29).




Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection
PMID: 29728610

Recently, deficiency in the cytosolic DNA sensor RNA Polymerase III was described in children with severe primary varicella-zoster virus (VZV) infection in the CNS and lungs. In the present study we examined adult patients with VZV CNS infection caused by viral reactivation. By whole exome sequencing we identified mutations in POL III genes in two of eight patients. These mutations were located in the coding regions of the subunits POLR3A and POLR3E. In functional assays, we found impaired expression of antiviral and inflammatory cytokines in response to the POL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, this study provides significant extension on the current knowledge on susceptibility to VZV infection by demonstrating mutations in POL III genes associated with impaired immunological sensing of AT-rich DNA in adult patients with VZV CNS infection.; to: This gene is responsible for A subunit of Polymerase which senses DNA viruses especially AT-rich regions eg Varicella Zoster. SARS-CoV-2 is an RNA virus.

Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections(PMID: 28783042)

We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). POLR3A and POLR3C encode subunits of RNA polymerase III. Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA. Moreover, leukocytes from 3 of the patients displayed defective IFN production upon VZV infection and reduced control of VZV replication. These phenotypes were rescued by transduction with relevant WT alleles. This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity
Different classes of PRRs are involved in recognition of virus infections, including membrane-associated TLRs; cytosolic retinoic acid–inducible gene 1–like (RIG-I–like) receptors, which sense RNA; and DNA sensors (24). Each of these classes of PRRs stimulates production of IFNs, which exhibit antiviral activity through their ability to induce IFN-stimulated genes (ISGs). With respect to DNA sensors, TLR9 detects unmethylated DNA, RNA polymerase III (POL III) recognizes AT-rich DNA, while gamma-interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) sense double-stranded DNA in a sequence-independent manner (25–29).




Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection
PMID: 29728610

Recently, deficiency in the cytosolic DNA sensor RNA Polymerase III was described in children with severe primary varicella-zoster virus (VZV) infection in the CNS and lungs. In the present study we examined adult patients with VZV CNS infection caused by viral reactivation. By whole exome sequencing we identified mutations in POL III genes in two of eight patients. These mutations were located in the coding regions of the subunits POLR3A and POLR3E. In functional assays, we found impaired expression of antiviral and inflammatory cytokines in response to the POL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, this study provides significant extension on the current knowledge on susceptibility to VZV infection by demonstrating mutations in POL III genes associated with impaired immunological sensing of AT-rich DNA in adult patients with VZV CNS infection.
COVID-19 research v0.81 POLR3A Abdelazeem Elhabyan reviewed gene: POLR3A: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28783042,29728610; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 ACE Abdelazeem Elhabyan reviewed gene: ACE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 NRAS Abdelazeem Elhabyan reviewed gene: NRAS: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21595878,12670913,; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 MRE11 Abdelazeem Elhabyan reviewed gene: MRE11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 MPO Abdelazeem Elhabyan reviewed gene: MPO: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27574522,21703402,29325098,29769163,24968347; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 KRAS Abdelazeem Elhabyan reviewed gene: KRAS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 GUCY2C Abdelazeem Elhabyan reviewed gene: GUCY2C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 FPR2 Abdelazeem Elhabyan reviewed gene: FPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28928730, 27034344,29738458,31398292,29127186; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.81 FPR2 Abdelazeem Elhabyan Deleted their review
COVID-19 research v0.81 FPR2 Abdelazeem Elhabyan commented on gene: FPR2
COVID-19 research v0.81 MRE11 Sarah Leigh Classified gene: MRE11 as Amber List (moderate evidence)
COVID-19 research v0.81 MRE11 Sarah Leigh Added comment: Comment on list classification: Immunodeficiency does not appear to be a feature of Ataxia-telangiectasia-like disorder 1 604391. However, as part of the MRE11-RAD50-NBS1 Complex it is part of the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection (pmid 29709199). Hence, variants in MRE11, could reduce the response to viral DNA integration in host cells,allowing infections to be propogated.
COVID-19 research v0.81 MRE11 Sarah Leigh Gene: mre11 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.80 MRE11 Sarah Leigh Publications for gene: MRE11 were set to 8445618; 10612394; 15574463; 32212377
COVID-19 research v0.79 MRE11 Sarah Leigh Classified gene: MRE11 as Red List (low evidence)
COVID-19 research v0.79 MRE11 Sarah Leigh Added comment: Comment on list classification: Immunodeficiency does not appear to be a feature of Ataxia-telangiectasia-like disorder 1 604391
COVID-19 research v0.79 MRE11 Sarah Leigh Gene: mre11 has been classified as Red List (Low Evidence).
COVID-19 research v0.78 MRE11 Sarah Leigh Publications for gene: MRE11 were set to 10612394; 8445618; 15574463
COVID-19 research v0.77 SNORA31 Catherine Snow Classified gene: SNORA31 as Green List (high evidence)
COVID-19 research v0.77 SNORA31 Catherine Snow Added comment: Comment on list classification: Rating Green following external review
COVID-19 research v0.77 SNORA31 Catherine Snow Gene: snora31 has been classified as Green List (High Evidence).
COVID-19 research v0.76 POLR3A Rebecca Foulger changed review comment from: Added POLR3A to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel: https://panelapp.agha.umccr.org/panels/237/; to: Added POLR3A to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel V0.22: https://panelapp.agha.umccr.org/panels/237/
COVID-19 research v0.76 POLR3C Rebecca Foulger changed review comment from: Added POLR3C to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel: https://panelapp.agha.umccr.org/panels/237/; to: Added POLR3C to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel V0.22: https://panelapp.agha.umccr.org/panels/237/
COVID-19 research v0.76 POLR3F Rebecca Foulger changed review comment from: Added POLR3F to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel: https://panelapp.agha.umccr.org/panels/237/; to: Added POLR3F to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel V0.22: https://panelapp.agha.umccr.org/panels/237/
COVID-19 research v0.76 POLR3F Rebecca Foulger commented on gene: POLR3F
COVID-19 research v0.76 POLR3C Rebecca Foulger commented on gene: POLR3C
COVID-19 research v0.76 POLR3A Rebecca Foulger commented on gene: POLR3A
COVID-19 research v0.76 POLR3F Rebecca Foulger gene: POLR3F was added
gene: POLR3F was added to Viral susceptibility. Sources: Expert Review Red,Victorian Clinical Genetics Services,Expert list
Mode of inheritance for gene: POLR3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3F were set to 30211253
Phenotypes for gene: POLR3F were set to Severe VZV infection
COVID-19 research v0.76 POLR3C Rebecca Foulger gene: POLR3C was added
gene: POLR3C was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,Expert list,Expert Review Amber
Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3C were set to 28783042
Phenotypes for gene: POLR3C were set to Severe VZV infection
COVID-19 research v0.76 POLR3A Rebecca Foulger gene: POLR3A was added
gene: POLR3A was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,Expert list,Expert Review Amber
Mode of inheritance for gene: POLR3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3A were set to 29728610; 28783042
Phenotypes for gene: POLR3A were set to Severe VZV infection
COVID-19 research v0.75 DBR1 Abdelazeem Elhabyan changed review comment from: I found that it has been promoted from the Australling susceptibility to viral infections on this link
https://panelapp.agha.umccr.org/panels/237/gene/DBR1/
This is based on this notion :
Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants.

When I reviewed the paper, I found a notion of influenza viral encephalitis among other viruses(eg HSV-1) and a suggestion that this predisposition to the disease is due to involvement of DBR1 in intrinsic resistance of brainstem cells to those viruses via the enzyme encoded by DBR1.; to: I found that it has been promoted from the Australling susceptibility to viral infections on this link
https://panelapp.agha.umccr.org/panels/237/gene/DBR1/

This is based on this notion in this paper :
https://pubmed.ncbi.nlm.nih.gov/29474921/
Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants.

When I reviewed the paper, I found a notion of influenza viral encephalitis among other viruses(eg HSV-1) and a suggestion that this predisposition to the disease is due to the involvement of DBR1 in intrinsic resistance of brainstem cells to those viruses via the enzyme encoded by DBR1.
COVID-19 research v0.75 DBR1 Abdelazeem Elhabyan commented on gene: DBR1: I found that it has been promoted from the Australling susceptibility to viral infections on this link
https://panelapp.agha.umccr.org/panels/237/gene/DBR1/
This is based on this notion :
Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants.

When I reviewed the paper, I found a notion of influenza viral encephalitis among other viruses(eg HSV-1) and a suggestion that this predisposition to the disease is due to involvement of DBR1 in intrinsic resistance of brainstem cells to those viruses via the enzyme encoded by DBR1.
COVID-19 research v0.75 MRE11 Sarah Leigh Publications for gene: MRE11 were set to 10612394; 8445618
COVID-19 research v0.74 FPR3 Catherine Snow changed review comment from: Formyl peptide receptors (FPRs) are classical chemoattractant receptors and although recently identified as being expressed in a sepsis patient derived neutrophils (PMID: 31982133) there is not enough evidence to upgrade to Amber.; to: Formyl peptide receptors (FPRs) are classical chemoattractant receptors and although FPR3 was recently identified as being expressed in a sepsis patient derived neutrophils (PMID: 31982133) there is not enough evidence to upgrade to Amber.
COVID-19 research v0.74 FPR3 Catherine Snow reviewed gene: FPR3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.74 FPR2 Catherine Snow changed review comment from: FPR2 is a seven transmembrane G protein-coupled receptor, which plays an important role in sensing of bacteria and modulation of immune responses

Mouse model PMID: 31908042 Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals

PMID: 28928730 The review gives an overview on the pathogenesis of influenza with a focus on the role of FPR2 and discusses the advantages of using FPR2 antagonists to treat the flu. Preclinical studies have proven that FPR2 antagonists efficiently protect mice against IAV infections, by inhibiting viral replication and deleterious inflammation of the lungs; to: FPR2 is a seven transmembrane G protein-coupled receptor, which plays an important role in sensing of bacteria and modulation of immune responses

Mouse model PMID: 31908042 Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals

PMID: 28928730 The review gives an overview on the pathogenesis of influenza with a focus on the role of FPR2 and discusses the advantages of using FPR2 antagonists to treat the flu. Preclinical studies have proven that FPR2 antagonists efficiently protect mice against IAV infections, by inhibiting viral replication and deleterious inflammation of the lungs
COVID-19 research v0.74 FPR2 Catherine Snow changed review comment from: FPR2 is a seven transmembrane G protein-coupled receptor, which plays an important role in sensing of bacteria and modulation of immune responses

Mouse model PMID: 31908042 Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals

PMID: 28928730 The review gives an overview on the pathogenesis of influenza with a focus on the role of FPR2 and discusses the advantages of using FPR2 antagonists to treat the flu. Preclinical studies have proven that FPR2 antagonists efficiently protect mice against IAV infections, by inhibiting viral replication and deleterious inflammation of the lungs; to: FPR2 is a seven transmembrane G protein-coupled receptor, which plays an important role in sensing of bacteria and modulation of immune responses

Mouse model PMID: 31908042 Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals

PMID: 28928730 The review gives an overview on the pathogenesis of influenza with a focus on the role of FPR2 and discusses the advantages of using FPR2 antagonists to treat the flu. Preclinical studies have proven that FPR2 antagonists efficiently protect mice against IAV infections, by inhibiting viral replication and deleterious inflammation of the lungs
COVID-19 research v0.74 FPR2 Catherine Snow Classified gene: FPR2 as Amber List (moderate evidence)
COVID-19 research v0.74 FPR2 Catherine Snow Gene: fpr2 has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.73 FPR2 Catherine Snow reviewed gene: FPR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31908042, 28928730; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.73 FCGRT Catherine Snow Classified gene: FCGRT as Red List (low evidence)
COVID-19 research v0.73 FCGRT Catherine Snow Added comment: Comment on list classification: No association found.
COVID-19 research v0.73 FCGRT Catherine Snow Gene: fcgrt has been classified as Red List (Low Evidence).
COVID-19 research v0.72 FCGR3B Catherine Snow Classified gene: FCGR3B as Red List (low evidence)
COVID-19 research v0.72 FCGR3B Catherine Snow Added comment: Comment on list classification: Comment on list classification: No link to viral susceptibility some evidence of FCGR3B that variants give rise to susceptibility to develop auto-immune diseases including SLE (PMID: 26683154).
COVID-19 research v0.72 FCGR3B Catherine Snow Gene: fcgr3b has been classified as Red List (Low Evidence).
COVID-19 research v0.71 FCGR2B Catherine Snow changed review comment from: Comment on list classification: No link to viral susceptibility some evidence of FCGR2B some evidence that variants give rise to susceptibility to develop auto-immune diseases (PMID: 26683154); to: Comment on list classification: No link to viral susceptibility some evidence of FCGR2B that variants give rise to susceptibility to develop auto-immune diseases (PMID: 26683154)
COVID-19 research v0.71 FCGR2B Catherine Snow changed review comment from: Comment on list classification: No link to viral susceptibility some evidence of FCGR2B some evidence that variants give rise to susceptibility to develop auto-immune diseases; to: Comment on list classification: No link to viral susceptibility some evidence of FCGR2B some evidence that variants give rise to susceptibility to develop auto-immune diseases (PMID: 26683154)
COVID-19 research v0.71 FCGR2B Catherine Snow Classified gene: FCGR2B as Red List (low evidence)
COVID-19 research v0.71 FCGR2B Catherine Snow Added comment: Comment on list classification: No link to viral susceptibility some evidence of FCGR2B some evidence that variants give rise to susceptibility to develop auto-immune diseases
COVID-19 research v0.71 FCGR2B Catherine Snow Gene: fcgr2b has been classified as Red List (Low Evidence).
COVID-19 research v0.70 FCGR2A Catherine Snow Publications for gene: FCGR2A were set to 16185324
COVID-19 research v0.69 FCGR2A Catherine Snow Mode of inheritance for gene: FCGR2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
COVID-19 research v0.68 FCGR2A Catherine Snow Classified gene: FCGR2A as Green List (high evidence)
COVID-19 research v0.68 FCGR2A Catherine Snow Gene: fcgr2a has been classified as Green List (High Evidence).
COVID-19 research v0.67 FCGR2A Catherine Snow Tag watchlist tag was added to gene: FCGR2A.
Tag polygenic tag was added to gene: FCGR2A.
COVID-19 research v0.67 FCGR2A Catherine Snow reviewed gene: FCGR2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19494086, 12752683, 16185324; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.67 NRAS Ellen McDonagh Mode of inheritance for gene: NRAS was changed from Unknown to Other
COVID-19 research v0.66 IL17A Ivone Leong Classified gene: IL17A as Green List (high evidence)
COVID-19 research v0.66 IL17A Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green as there is enough evidence in the literature to support this.
COVID-19 research v0.66 IL17A Ivone Leong Gene: il17a has been classified as Green List (High Evidence).
COVID-19 research v0.65 IRF2BP2 Eleanor Williams Phenotypes for gene: IRF2BP2 were changed from Recurrent infections, possible autoimmunity and inflammatory disease; Predominantly Antibody Deficiencies; CVID to Recurrent infections, possible autoimmunity and inflammatory disease; Predominantly Antibody Deficiencies; CVID; Immunodeficiency, common variable, 14, MIM# 617765
COVID-19 research v0.64 IRF2BP2 Eleanor Williams Publications for gene: IRF2BP2 were set to 27016798; 32086639; 32048120
COVID-19 research v0.62 IRF2BP2 Eleanor Williams commented on gene: IRF2BP2
COVID-19 research v0.62 DBR1 Louise Daugherty Deleted their review
COVID-19 research v0.62 DBR1 Louise Daugherty Deleted their comment
COVID-19 research v0.62 FCGR1A Catherine Snow Classified gene: FCGR1A as Red List (low evidence)
COVID-19 research v0.62 FCGR1A Catherine Snow Added comment: Comment on list classification: FCGR1 is on the Immunoplex Panel offered by the University of Washington Department of Laboratory Medicine however there is currently no link to alleles and disease (PMID: 31057544)
COVID-19 research v0.62 FCGR1A Catherine Snow Gene: fcgr1a has been classified as Red List (Low Evidence).
COVID-19 research v0.61 ADAM17 Abdelazeem Elhabyan reviewed gene: ADAM17: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.61 ADAM17 Abdelazeem Elhabyan Deleted their review
COVID-19 research v0.61 ADAM17 Abdelazeem Elhabyan reviewed gene: ADAM17: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.61 ACTB Abdelazeem Elhabyan reviewed gene: ACTB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.60 DBR1 Louise Daugherty changed review comment from: PanelApp curators : you might need to re-review all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are POLE2, BRCA1, BRCA2, ERCC4 etc unless there is evidence missed from the upload?; to: PanelApp curators : you might need to re-review all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are IFNAR2, POLE2, BRCA1, BRCA2, ERCC4 etc unless there is evidence missed from the upload?
COVID-19 research v0.60 DBR1 Louise Daugherty changed review comment from: PanelApp curators : you might need to all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are POLE2, BRCA1, BRCA2, ERCC4 etc unless there is evidence missed from the upload?; to: PanelApp curators : you might need to re-review all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are POLE2, BRCA1, BRCA2, ERCC4 etc unless there is evidence missed from the upload?
COVID-19 research v0.60 DBR1 Louise Daugherty changed review comment from: PanelApp curators : you might need to all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are POLE2, BRCA1, BRCA2, ERCC4 etc unless there as evidence missed from the upload?; to: PanelApp curators : you might need to all the Green genes on this panel that were previously rated as Red on the PID panel, there may have been an error with the automatic upload changing Red Genes to Expert Review Green (https://panelapp.genomicsengland.co.uk/panels/398/gene/DBR1/), other examples are POLE2, BRCA1, BRCA2, ERCC4 etc unless there is evidence missed from the upload?
COVID-19 research v0.60 DBR1 Louise Daugherty reviewed gene: DBR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.60 MPO Sarah Leigh Classified gene: MPO as Amber List (moderate evidence)
COVID-19 research v0.60 MPO Sarah Leigh Added comment: Comment on list classification: PMID 3208230 outlines the role of neutrophil extracellular traps (NETs) in the control of some pathogens including viruses, by virus capture and neutralization. In vivo treatment of the mice with DNase resulted in the enhanced susceptibility of IFNAR-/- mice to the CHIKV virus. Furthermore, the levels of MPO-DNA complex in acutely CHIKV-infected patients, were correlated with the levels of NETs and the viral load in the blood, suggesting that NETs are also released in natural human infection cases. Therefore, variants that result in myeloperoxidase deficiency, may well contribute to an increased susceptiblity to viral infection.
At least 9 variants have been reported in Myeloperoxidase deficiency 254600 and these could well be contributing to increased viral susceptibily.
COVID-19 research v0.60 MPO Sarah Leigh Gene: mpo has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.59 C17orf62 Abdelazeem Elhabyan Deleted their review
COVID-19 research v0.59 C17orf62 Abdelazeem Elhabyan reviewed gene: C17orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.59 DBR1 Abdelazeem Elhabyan reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.59 IL17A Abdelazeem Elhabyan commented on gene: IL17A: I agree that the level should be reviewed for being increased to Green especially the association of SNPs with H1N1 (influenza A) and influenza B.


Association with CNVs with pathology has been confirmed but the disease state was not revealed in any of the patients
https://www.ncbi.nlm.nih.gov/clinvar?LinkName=gene_clinvar&from_uid=3605
COVID-19 research v0.59 IL17A Abdelazeem Elhabyan edited their review of gene: IL17A: Changed rating: GREEN
COVID-19 research v0.59 IL17A Abdelazeem Elhabyan Deleted their comment
COVID-19 research v0.59 IL17A Abdelazeem Elhabyan changed review comment from: I agree that the level should be reviewed for being increased to Green especially the association of SNPs with H1N1 (influenza A) and influenza B.


Association with CNVs with pathology has been confirmed but the disease state was not revealed in any of the patients
https://www.ncbi.nlm.nih.gov/clinvar?LinkName=gene_clinvar&from_uid=3605; to: I agree that the level should be reviewed for being increased to Green especially the association of SNPs with H1N1 (influenza A) and influenza B.


Association with CNVs with pathology has been confirmed but the disease state was not revealed in any of the patients
https://www.ncbi.nlm.nih.gov/clinvar?LinkName=gene_clinvar&from_uid=3605
COVID-19 research v0.59 IL17A Abdelazeem Elhabyan commented on gene: IL17A
COVID-19 research v0.59 IRF9 Abdelazeem Elhabyan commented on gene: IRF9
COVID-19 research v0.59 ACP5 Abdelazeem Elhabyan reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.59 IGHG2 Ivone Leong reviewed gene: IGHG2: Rating: ; Mode of pathogenicity: None; Publications: 16092453; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.59 HLA-B Ivone Leong Publications for gene: HLA-B were set to 12969506
COVID-19 research v0.58 IL17A Ivone Leong Classified gene: IL17A as Amber List (moderate evidence)
COVID-19 research v0.58 IL17A Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. There appears to be enough evidence for this gene to be promoted Green; however, will wait for expert review before promoting to Green.
COVID-19 research v0.58 IL17A Ivone Leong Gene: il17a has been classified as Amber List (Moderate Evidence).
COVID-19 research v0.57 IL17A Ivone Leong Phenotypes for gene: IL17A were changed from Arthritis; Immunodeficiency 5 to Arthritis; Immunodeficiency 5; Susceptibility to influenza
COVID-19 research v0.56 IL17A Ivone Leong Mode of inheritance for gene: IL17A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
COVID-19 research v0.55 IL17A Ivone Leong Publications for gene: IL17A were set to
COVID-19 research v0.54 IL17A Ivone Leong reviewed gene: IL17A: Rating: ; Mode of pathogenicity: None; Publications: 28860146, 31196204, 27890033, 21703407, 27155288, 29530464; Phenotypes: ; Mode of inheritance: Unknown
COVID-19 research v0.54 GAD1 Catherine Snow Classified gene: GAD1 as Red List (low evidence)
COVID-19 research v0.54 GAD1 Catherine Snow Added comment: Comment on list classification: GAD1 has no relationship to virus susceptibility.
COVID-19 research v0.54 GAD1 Catherine Snow Gene: gad1 has been classified as Red List (Low Evidence).
COVID-19 research v0.53 EPCAM Catherine Snow Classified gene: EPCAM as Red List (low evidence)
COVID-19 research v0.53 EPCAM Catherine Snow Added comment: Comment on list classification: No gene disease association.
COVID-19 research v0.53 EPCAM Catherine Snow Gene: epcam has been classified as Red List (Low Evidence).
COVID-19 research v0.52 IFNAR1 Sarah Leigh Classified gene: IFNAR1 as Green List (high evidence)
COVID-19 research v0.52 IFNAR1 Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. However, the publications listed below give evidence that the three LOF variants in two unrelated cases are associated with an adverse reaction to attenuated virus vaccines, which are rescued by wt IFNAR1 protein in vitro.
COVID-19 research v0.52 IFNAR1 Sarah Leigh Gene: ifnar1 has been classified as Green List (High Evidence).
COVID-19 research v0.51 IFNAR1 Sarah Leigh Added comment: Comment on publications: PMID 31270247: reports three variants in two cases of healthy children with adverse reactions to live attuated virus vaccines. Each had biallelic loss-of-function IFNAR1 variations and the effects of these was demonstrated by the patient-derived fibroblasts being susceptible to viruses. This effect was recused by the WT IFNAR1.
PMID 26676772: reports the tageted degradation of IFNAR1 protein by
Influenza A virus (IAV), allowing the virus to escape the powerful innate immune system. Thus the loss of function of IFNAR1 would increase the susceptability to viral infection.
PMID 20020050: reports the tageted degradation of IFNAR1 protein by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells.
COVID-19 research v0.51 IFNAR1 Sarah Leigh Publications for gene: IFNAR1 were set to 31270247; 26676772; 20020050
COVID-19 research v0.50 UNC119 Eleanor Williams commented on gene: UNC119: Checked OMIM and literature (through PubMed) for updates in April 2020 - no new cases reported. Keep red.
COVID-19 research v0.50 STAT5A Eleanor Williams Publications for gene: STAT5A were set to 16418296
COVID-19 research v0.49 STAT5A Eleanor Williams edited their review of gene: STAT5A: Added comment: April 2020
- no association with any human disease phenotype in OMIM (page last updated Feb 2020).
- no associations in Gene2Phenotype.
- PubMed search - no publications describing reports of variants in STAT5 and PID/viral susceptibility but :

PMID: 26541527- Leahy et al 2016 - mention that STAT5 mRNA (which is in the IL-15 pathway) is differentially expressed in children with severe bronchiolitis compared with those with moderate severity bronchiolitis.
PMID: 23593005- Hong et al 2013 - in human papillomavirus (HPV) infections STAT-5 is activated as part of the process to regulate genome amplification in suprabasal cells.
PMID: 22520852 - Li et al - show in mouse studies that tetramerization of STAT5 is critical for cytokine responses and normal immune function; Changed publications: 16418296, 26541527, 23593005, 22520852
COVID-19 research v0.49 IRF9 Catherine Snow Classified gene: IRF9 as Green List (high evidence)
COVID-19 research v0.49 IRF9 Catherine Snow Added comment: Comment on list classification: Rating Green on this panel following feedback with Genomics England clinical team, as this is a research panel and IRF9 has two unrelated cases and an animal model.
COVID-19 research v0.49 IRF9 Catherine Snow Gene: irf9 has been classified as Green List (High Evidence).
COVID-19 research v0.48 HLA-B Ivone Leong reviewed gene: HLA-B: Rating: ; Mode of pathogenicity: None; Publications: 15243926, 18186801; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.48 CCL2 Rebecca Foulger Publications for gene: CCL2 were set to 25818534; 26687605; 16916890; 24788844
COVID-19 research v0.47 CCL2 Rebecca Foulger commented on gene: CCL2: PMID:27260136 (Kim et al., 2016) report that CCL2 ablation highly increased susceptibility to Japanese encephalitis, indicating that CCL2 plays an essential role in conferring protection against JE caused by JE virus (JEV) infection. They also note a surprising opposite effect for ablation of the CCR2 (the corresponding receptor).
COVID-19 research v0.47 CCL2 Rebecca Foulger Publications for gene: CCL2 were set to 25818534; 26687605; 16916890
COVID-19 research v0.46 CCL2 Rebecca Foulger commented on gene: CCL2: PMID:24788844 (Han et al., 2014) studied 36 Chines patients and report that the CCL2-2510G allele is associated with susceptibility to EV71 encephalitis in Chinese patients.
COVID-19 research v0.46 CCL2 Rebecca Foulger Phenotypes for gene: CCL2 were changed from Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection; Susceptibility to SARS-CoV to {HIV-1, resistance to}, 609423; Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection; Susceptibility to SARS-CoV
COVID-19 research v0.45 CCL2 Rebecca Foulger commented on gene: CCL2: PMID:16916890 (Ansari et al.) report increased CCL2 levels in HIV-1 patients, and suggest inhibition of CCL2 production could provide a therapeutic intervention in HIV infection.
COVID-19 research v0.45 CCL2 Rebecca Foulger Publications for gene: CCL2 were set to 25818534
COVID-19 research v0.44 CCL2 Rebecca Foulger commented on gene: CCL2
COVID-19 research v0.44 IRF2BP2 Zornitza Stark reviewed gene: IRF2BP2: Rating: RED; Mode of pathogenicity: None; Publications: 27016798; Phenotypes: Immunodeficiency, common variable, 14, MIM# 617765; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research v0.44 MPO Sarah Leigh Publications for gene: MPO were set to 9354683; 15108282; 9637725
COVID-19 research v0.43 ACE Rebecca Foulger Marked gene: ACE as ready
COVID-19 research v0.43 ACE Rebecca Foulger Gene: ace has been classified as Red List (Low Evidence).
COVID-19 research v0.43 KRAS Rebecca Foulger Added comment: Comment on mode of inheritance: Autosomal (AD) inheritance listed in OMIM for MIM:614470.
COVID-19 research v0.43 KRAS Rebecca Foulger Mode of inheritance for gene: KRAS was changed from Unknown to Unknown
COVID-19 research v0.42 KRAS Rebecca Foulger commented on gene: KRAS
COVID-19 research v0.42 KRAS Rebecca Foulger Phenotypes for gene: KRAS were changed from RAS associated lymphoproliferative disease, 614470; RALD to RALD; RAS-associated autoimmune leukoproliferative disorder, 614470
COVID-19 research v0.41 IRF8 Ellen McDonagh Classified gene: IRF8 as Green List (high evidence)
COVID-19 research v0.41 IRF8 Ellen McDonagh Gene: irf8 has been classified as Green List (High Evidence).
COVID-19 research v0.40 KDM6A Ellen McDonagh Source Expert Review Green was added to KDM6A.
Added phenotypes Combined immunodeficiencies with associated or syndromic features; Kabuki Syndrome 2 due to KDM6A deficiency; Typical facial abnormalities, cleft or high arched palate, skeletal abnormalities, short stature, intellectual disability, congenital heart defects, recurrent infections (otitis media, pneumonia) in 50% of patients. Autoimmunity may be present for gene: KDM6A
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SH3KBP1 Ellen McDonagh Source Expert Review Green was added to SH3KBP1.
Added phenotypes Predominantly Antibody Deficiencies; Severe bacterial infections; SH3KBP1 (CIN85) deficiency; Immunodeficiency 61, 300310 for gene: SH3KBP1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IRAK1 Ellen McDonagh Source Expert Review Green was added to IRAK1.
Added phenotypes Bacterial infections, X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1; Defects in Intrinsic and Innate Immunity for gene: IRAK1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TRAF3 Ellen McDonagh Added phenotypes Herpetic encephalitis (HSE); Herpes simplex virus 1 encephalitis; Defects in Intrinsic and Innate Immunity; Defects in intrinsic and innate immunity; {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849; Herpes simplex encephalitis, susceptibility to, 3 for gene: TRAF3
COVID-19 research v0.40 TOP2B Ellen McDonagh Source Expert Review Green was added to TOP2B.
Added phenotypes Recurrent infections, facial dysmorphism, limb anomalies; Hoffman syndrome/TOP2B deficiency; Predominantly Antibody Deficiencies for gene: TOP2B
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFSF12 Ellen McDonagh Source Expert Review Green was added to TNFSF12.
Added phenotypes Immunodeficiency, common variable with lack of anti-pneumococcal antibody; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Pneumonia, bacterial infections, warts, thrombocytopenia. neutropenia; Pneumonia, bacterial infections, warts, thrombocytopenia for gene: TNFSF12
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 THBD Ellen McDonagh Source Expert Review Green was added to THBD.
Added phenotypes Complement Deficiencies; Thrombomodulin deficiency; Hemolytic uremic syndrome, atypical, susceptibility to, 6; Atypical hemolytic-uremic syndrome for gene: THBD
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TGFBR2 Ellen McDonagh Source Expert Review Green was added to TGFBR2.
Added phenotypes Recurrent respiratory infections, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms; Combined immunodeficiencies with associated or syndromic features; ALPS-FAS for gene: TGFBR2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TGFBR1 Ellen McDonagh Source Expert Review Green was added to TGFBR1.
Added phenotypes Loeys-Dietz syndrome 1, 609192; Loeys Dietz syndrome due to TGFBR1 deficiency; Combined immunodeficiencies with associated or syndromic features; Recurrent respiratory infectons, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms for gene: TGFBR1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SRP54 Ellen McDonagh Source Expert Review Green was added to SRP54.
Added phenotypes Schwachman Diamond features; Congenital defects of phagocyte number or function for gene: SRP54
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SH3BP2 Ellen McDonagh Source Expert Review Green was added to SH3BP2.
Added phenotypes Other autoinflammatory diseases with known genetic defect; Autoinflammatory Disorders; Cherubism 118400; Bone degeneration in jaws for gene: SH3BP2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SEMA3E Ellen McDonagh Source Expert Review Green was added to SEMA3E.
Added phenotypes CHARGE syndrome; immune-mediated cerebellar ataxia; Coloboma, heart anomaly, choanal atresia, intellectual retardation, genital and ear anomalies, CNS malformation, some are SCID-like and have low TRECs; Charge syndrome 214800; Combined immunodeficiencies with associated or syndromic features for gene: SEMA3E
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SEC61A1 Ellen McDonagh Source Expert Review Green was added to SEC61A1.
Added phenotypes Severe recurrent respiratory tract infections; Predominantly Antibody Deficiencies; Hyperuricemic nephropathy, familial juvenile, 4, 617056; SEC61A1 deficiency for gene: SEC61A1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 RELA Ellen McDonagh Source Expert Review Green was added to RELA.
Added phenotypes RelA haplosufficiency; Mucosal ulceration, impaired NFkB activation; Mucocutaneous ulceration, chronic, 618287; Immunodeficiencies affecting cellular and humoral immunity for gene: RELA
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 RANBP2 Ellen McDonagh Source Expert Review Green was added to RANBP2.
Added phenotypes Fever induces acute encephalopathy; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity for gene: RANBP2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 PSEN1 Ellen McDonagh Source Expert Review Green was added to PSEN1.
Added phenotypes Hidradenitis suppurative with cutaneous hyperpigmentation; Acne inversa, familial, 3 613737; Defects in Intrinsic and Innate Immunity for gene: PSEN1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 OAS1 Ellen McDonagh Source Expert Review Green was added to OAS1.
Added phenotypes OAS1 GOF; Autoinflammatory Disorders; Pulmonary alveolar proteinosis, skin rash for gene: OAS1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 NFE2L2 Ellen McDonagh Source Expert Review Green was added to NFE2L2.
Added phenotypes Recurrent respiratory and skin infections, growth retardation, , developmental delay; increased expression of stress response genes; Immunodeficiency, developmental delay, and hypohomocysteinemia, 617744; white matter cerebral lesions, increased level of homocysteine; Combined immunodeficiencies with associated or syndromic features; NFE2L2 GOF for gene: NFE2L2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 NFAT5 Ellen McDonagh Source Expert Review Green was added to NFAT5.
Added phenotypes NFAT5 haploinsufficieny; IBD, recurrent sinopulmonary infections; Diseases of Immune Dysregulation for gene: NFAT5
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 KMT2D Ellen McDonagh Source Expert Review Green was added to KMT2D.
Added phenotypes Kabuki syndrome 1, 147920; Combined immunodeficiencies with associated or syndromic features; Typical facial abnormalities, cleft or high arched palate, skeletal abnormalities, short stature, intellectual disability, congenital heart defects, recurrent infections (otitis media, pneumonia) in 50% of patients. Autoimmunity may be present for gene: KMT2D
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 KMT2A Ellen McDonagh Source Expert Review Green was added to KMT2A.
Added phenotypes Wiedemann-Steiner syndrome with Congenital immunodeficiency; Combined immunodeficiencies with associated or syndromic features; Unclassified antibody deficiency; Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability for gene: KMT2A
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 JAK1 Ellen McDonagh Source Expert Review Green was added to JAK1.
Added phenotypes Hypereosinophilic syndrome; HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections; Diseases of Immune Dysregulation; Susceptibility to mycobacteria and viruses, urothelial carcinoma; Defects in Intrinsic and Innate Immunity; HSM, eosinophilic enteritis, thyroid disease, poor growth, viral infections for gene: JAK1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IRF2BP2 Ellen McDonagh Source Expert Review Green was added to IRF2BP2.
Added phenotypes Recurrent infections, possible autoimmunity and inflammatory disease; Predominantly Antibody Deficiencies; CVID for gene: IRF2BP2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ERBIN Ellen McDonagh Source Expert Review Green was added to ERBIN.
Added phenotypes ERBIN deficiency; Combined immunodeficiencies with associated or syndromic features; Recurrent respiratory infections, susceptibility to S. aureus, eczema, hyperextensible joints, scoliosis, arterial dilatation in some for gene: ERBIN
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 BCL11B Ellen McDonagh Source Expert Review Green was added to BCL11B.
Added phenotypes Combined immunodeficiencies with associated or syndromic features; leaky SCID; ?Immunodeficiency 49, 617237; Immunodeficiencies affecting cellular and humoral immunity; Congenital abnormalities, neonatal teeth, dysmorphic facies, absent corpus callosum, neurocognitive deficits for gene: BCL11B
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 APOL1 Ellen McDonagh Source Expert Review Green was added to APOL1.
Added phenotypes Defects in Intrinsic and Innate Immunity; Trypanosomiasis, susceptibility to; Trypanosomias; Trypanosomiasis for gene: APOL1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ACTB Ellen McDonagh Source Expert Review Green was added to ACTB.
Added phenotypes Congenital defects of phagocyte number or function; neutrophil dysfunction; Mental retardation, short stature; Actin beta deficiency (ACTB); Phagocytic disorder; Poor neutrophil chemotaxis, oxidative burst and actin remodeling. Thrombocytopenia; Baraitser-Winter syndrome 1, 243310 for gene: ACTB
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFRSF13B Ellen McDonagh Source Expert Review Green was added to TNFRSF13B.
Added phenotypes IgA with IgG subclass deficiency; Immunodeficiency, common variable, 2; Immunodeficiency, common variable, 2, 240500; Variable clinical expression; Isolated IgG subclass deficiency; IGAD; Selective IgA deficiency; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Immunoglobulin A deficiency 2, 609529; CVID for gene: TNFRSF13B
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 CFHR2 Ellen McDonagh Source Expert Review Green was added to CFHR2.
Added phenotypes Complement Deficiencies; Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ZNF341 Ellen McDonagh Source Expert Review Green was added to ZNF341.
Added phenotypes Hyper-IgE syndrome; Combined immunodeficiencies with associated or syndromic features; Bacterial infections, mild facial dysmorphism, pneumatoceles, hyperextensible joints, bone fractures, retention of primary teeth for gene: ZNF341
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 WRAP53 Ellen McDonagh Source Expert Review Green was added to WRAP53.
Added phenotypes Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; Combined immunodeficiencies with associated or syndromic features; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; microcephaly, neurodevelopmental delay for gene: WRAP53
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TRIM22 Ellen McDonagh Source Expert Review Green was added to TRIM22.
Added phenotypes TRIM22; Granulomatous colitis; Autoinflammatory Disorders; Diseases of Immune Dysregulation for gene: TRIM22
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TRAF3IP2 Ellen McDonagh Source Expert Review Green was added to TRAF3IP2.
Added phenotypes Defects in Intrinsic and Innate Immunity; Chronic mucocutaneous candidiasis (CMC); Defects in intrinsic and innate immunity; Candidiasis, familial, 8 615527; CMC, blepharitis, folliculitis and macroglossia for gene: TRAF3IP2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFSF11 Ellen McDonagh Source Expert Review Green was added to TNFSF11.
Added phenotypes Osteopetrosis with severe growth retardation; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity for gene: TNFSF11
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFRSF9 Ellen McDonagh Source Expert Review Green was added to TNFRSF9.
Added phenotypes EBV lymphoproliferation, B-cell lymphoma; CD137 deficiency (41BB) for gene: TNFRSF9
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFRSF4 Ellen McDonagh Source Expert Review Green was added to TNFRSF4.
Added phenotypes Kaposi's Sarcoma, impaired immunity to HHV8, OX40 deficiency; Immunodeficiencies affecting cellular and humoral immunity; Impaired immunity to HHV8, Kaposis sarcoma; Combined immunodeficiency for gene: TNFRSF4
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TIRAP Ellen McDonagh Source Expert Review Green was added to TIRAP.
Added phenotypes Staphylococcal disease during childhood; Defects of TLR/NFkappa-B signalling; TIRAP deficiency; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity for gene: TIRAP
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TGFB1 Ellen McDonagh Source Expert Review Green was added to TGFB1.
Added phenotypes Inflammatory bowel disease, immunodeficiency, and encephalopathy, 618213; IBD, immunodeficiency, recurrent viral infections, microcephaly, and encephalopathy; TGFB1 deficiency; Diseases of Immune Dysregulation for gene: TGFB1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TFRC Ellen McDonagh Source Expert Review Green was added to TFRC.
Added phenotypes Recurrent infections, neutropenia, thrombocytopenia; Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity for gene: TFRC
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TCIRG1 Ellen McDonagh Source Expert Review Green was added to TCIRG1.
Added phenotypes Defects in intrinsic and innate immunity; Osteopetrosis with hypocalcemia; Defects in Intrinsic and Innate Immunity for gene: TCIRG1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 STN1 Ellen McDonagh Source Expert Review Green was added to STN1.
Added phenotypes Combined immunodeficiencies with associated or syndromic features; Bone marrow failure; Intrauterine growth retardation, premature aging, pancytopenia, hypocellular bone marrow, gastrointestinal hemorrhage due to vascular ectasia, intracranial calcification, abnormal telomeres for gene: STN1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SNX10 Ellen McDonagh Source Expert Review Green was added to SNX10.
Added phenotypes Defects in intrinsic and innate immunity; Osteopetrosis with visual impairment; Defects in Intrinsic and Innate Immunity for gene: SNX10
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SMARCD2 Ellen McDonagh Source Expert Review Green was added to SMARCD2.
Added phenotypes Congenital defects of phagocyte number or function; Neutropenia, developmental aberrations, skeletal abnormalities, hematopoietic stem cells, myelodysplasia for gene: SMARCD2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SLC7A7 Ellen McDonagh Source Expert Review Green was added to SLC7A7.
Added phenotypes Lysinuric protein intolerance, 222700; Severe bacterial infections; Lysinuric protein intolerance SLC7A7 deficiency; Predominantly Antibody Deficiencies for gene: SLC7A7
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 SLC39A7 Ellen McDonagh Source Expert Review Green was added to SLC39A7.
Added phenotypes Agammaglobulinemia; B cell deficiency; Early onset infections, blistering dermatosis, failure to thrive, thrombocytopenia; Predominantly Antibody Deficiencies for gene: SLC39A7
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 RNU4ATAC Ellen McDonagh Source Expert Review Green was added to RNU4ATAC.
Added phenotypes Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature for gene: RNU4ATAC
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 RNF31 Ellen McDonagh Source Expert Review Green was added to RNF31.
Added phenotypes Polyglucosan body myopathy, early-onset, with or without immunodeficiency; Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis; autoinflammation and combined immunodeficiency; Combined immunodeficiencies with associated or syndromic features; Bacterial infections, autoinflammation, amylopectinosis, lymphangiectasia for gene: RNF31
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 RELB Ellen McDonagh Source Expert Review Green was added to RELB.
Added phenotypes Immunodeficiencies affecting cellular and humoral immunity; Recurrent infectionsImmunodeficiencies affecting cellular and humoral immunity; Recurrent infections; ?Immunodeficiency 53, 617585 for gene: RELB
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 REL Ellen McDonagh Source Expert Review Green was added to REL.
Added phenotypes Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic infections; Immunodeficiencies affecting cellular and humoral immunity; c-Rel deficiency for gene: REL
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 PSMG2 Ellen McDonagh Source Expert Review Green was added to PSMG2.
Added phenotypes Panniculitis, lipodystrophy, autoimmune hemolytic anemia; CANDLE (chronic atypical neutrophilic dermatitis with lipodystrophy); Autoinflammatory Disorders for gene: PSMG2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 POLE2 Ellen McDonagh Source Expert Review Green was added to POLE2.
Added phenotypes Recurrent infections, disseminated BCG infections, autoimmunity (type 1 diabetes, hypothyroidism, facial dysmorphism); Combined immunodeficiencies with associated or syndromic features; Recurrent infections, disseminated BCG infections, autoimmunity (type 1 diabetes, hypothyroidism, facial dysmorphism for gene: POLE2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 POLD2 Ellen McDonagh Source Expert Review Green was added to POLD2.
Added phenotypes Immunodeficiencies affecting cellular and humoral immunity; Polymerase d 2 deficiency; Recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability for gene: POLD2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 POLD1 Ellen McDonagh Source Expert Review Green was added to POLD1.
Added phenotypes Immunodeficiencies affecting cellular and humoral immunity; Recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability; Polymerase d 1 deficiency for gene: POLD1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 PLEKHM1 Ellen McDonagh Source Expert Review Green was added to PLEKHM1.
Added phenotypes Osteopetrosis; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity for gene: PLEKHM1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 OSTM1 Ellen McDonagh Source Expert Review Green was added to OSTM1.
Added phenotypes Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity; Osteopetrosis with hypocalcemia, neurologic features for gene: OSTM1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 NBAS Ellen McDonagh Source Expert Review Green was added to NBAS.
Added phenotypes Infantile liver failure syndrome 2, 616483; Defects in intrinsic and innate immunity; Fever induced liver failure; Defects in Intrinsic and Innate Immunity; Fever induces liver failure for gene: NBAS
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 MSH6 Ellen McDonagh Source Expert Review Green was added to MSH6.
Added phenotypes Colorectal cancer, hereditary nonpolyposis, type 5 614350; Endometrial cancer, familial 608089; Predominantly Antibody Deficiencies; Family or personal history of cancer; Mismatch repair cancer syndrome 276300 for gene: MSH6
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 MS4A1 Ellen McDonagh Source Expert Review Green was added to MS4A1.
Added phenotypes Predominantly Antibody Deficiencies; Recurrent infections; Common variable immunodeficiency disorders (CVID); Immunodeficiency, common variable, 5 613495 for gene: MS4A1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 MKL1 Ellen McDonagh Source Expert Review Green was added to MKL1.
Added phenotypes Susceptibility to severe bacterial infection; Mild thrombocytopenia; Congenital defects of phagocyte number or function for gene: MKL1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 MASP2 Ellen McDonagh Source Expert Review Green was added to MASP2.
Added phenotypes Complement Deficiencies; MASP2 deficiency 613791; Mannan-binding lectin serine protease (MASP) deficiency; Pyogenic infections, inflammatory lung disease, autoimmunity for gene: MASP2
Publications for gene MASP2 were updated from 24658431; 32086639; 32048120; 19405982 to 24658431; 32086639; 32048120; 19405982
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 LIG1 Ellen McDonagh Source Expert Review Green was added to LIG1.
Added phenotypes DNA ligase I deficiency; Combined immunodeficiencies with associated or syndromic features; DNA-ligase 1 ATP-dependent deficiency (LIG1); Recurrent respiratory infections, growth retardation, sun sensitivity, lymphoma, radiation sensitivity for gene: LIG1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IL6ST Ellen McDonagh Source Expert Review Green was added to IL6ST.
Added phenotypes Eczema; Abnormal acute-phase responses; Recurrent infections; Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis; Eosinophilia; Elevated IgE; Combined immunodeficiencies with associated or syndromic features for gene: IL6ST
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IL6R Ellen McDonagh Source Expert Review Green was added to IL6R.
Added phenotypes Eczema; Recurrent infections; Recurrent pyogenic infections, cold abscesses, high circulating IL-6 levels; Hyper-IgE; Combined immunodeficiencies with associated or syndromic features for gene: IL6R
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IL2RB Ellen McDonagh Source Expert Review Green was added to IL2RB.
Added phenotypes Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune hemolytic anemia, dermatitis, enteropathy, recurrent viral (EBV, CMV) infections; Immunodeficiency 63 with lymphoproliferation and autoimmunity, 618495; CD122 deficiency for gene: IL2RB
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 IFNAR2 Ellen McDonagh Source Expert Review Green was added to IFNAR2.
Added phenotypes ?Immunodeficiency 45, 616669; Severe viral infections (disseminated vaccine-strain measles, HHV6); Defects in Intrinsic and Innate Immunity for gene: IFNAR2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ICOSLG Ellen McDonagh Source Expert Review Green was added to ICOSLG.
Added phenotypes Immunodeficiencies affecting cellular and humoral immunity; Recurrent bacterial and viral infections for gene: ICOSLG
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 HYOU1 Ellen McDonagh Source Expert Review Green was added to HYOU1.
Added phenotypes Hypoglycemia, inflammatory complications; Congenital defects of phagocyte number or function for gene: HYOU1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 HMOX1 Ellen McDonagh Source Expert Review Green was added to HMOX1.
Added phenotypes amyloidosis; Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity for gene: HMOX1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 HAVCR2 Ellen McDonagh Source Expert Review Green was added to HAVCR2.
Added phenotypes T-cell lymphoma, subcutaneous panniculitis-like, 618398; Tim-3 deficiency; T-cell lymphoma, subcutaneous panniculitis-like, HLH; Autoinflammatory Disorders for gene: HAVCR2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FERMT1 Ellen McDonagh Source Expert Review Green was added to FERMT1.
Added phenotypes FERMT1 deficiency (Kindler syndrome); Diseases of Immune Dysregulation; Kindler syndrome, 173650; Dermatosis characterized by congenital blistering, skin atrophy, photosensitivity, skin fragility, and scaling for gene: FERMT1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FCN3 Ellen McDonagh Source Expert Review Green was added to FCN3.
Added phenotypes Respiratory infections, abscesses; Complement Deficiencies; Ficolin3 deficiency; Immunodeficiency due to ficolin 3 deficiency, 613860 for gene: FCN3
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FCHO1 Ellen McDonagh Source Expert Review Green was added to FCHO1.
Added phenotypes Recurrent infections, lymphoproliferation, increased activation-induced T-cell death, defective clathrin-mediated endocytosis; FCHO1 deficiency; Immunodeficiencies affecting cellular and humoral immunity for gene: FCHO1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FANCM Ellen McDonagh Source Expert Review Green was added to FANCM.
Added phenotypes Fanconi Anemia Type M; Bone marrow failure; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage for gene: FANCM
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FANCI Ellen McDonagh Source Expert Review Green was added to FANCI.
Added phenotypes Fanconi anemia, complementation group I, 609053; Bone marrow failure; Fanconi Anemia Type I; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage for gene: FANCI
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FANCF Ellen McDonagh Source Expert Review Green was added to FANCF.
Added phenotypes Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Fanconi anemia, complementation group F, 603467; Bone marrow failure; Fanconi Anemia Type F for gene: FANCF
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 FAAP24 Ellen McDonagh Source Expert Review Green was added to FAAP24.
Added phenotypes EBV infection-driven lymphoproliferative disease; Diseases of Immune Dysregulation for gene: FAAP24
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ERCC4 Ellen McDonagh Source Expert Review Green was added to ERCC4.
Added phenotypes Fanconi anemia, complementation group Q, 615272; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Fanconi Anemia Type Q; Bone marrow failure for gene: ERCC4
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 DEF6 Ellen McDonagh Source Expert Review Green was added to DEF6.
Added phenotypes DEF6 deficiency; Diseases of Immune Dysregulation; Enteropathy, hepatosplenomegaly, cardiomyopathy, recurrent infections for gene: DEF6
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 DBR1 Ellen McDonagh Source Expert Review Green was added to DBR1.
Added phenotypes DBR1 deficiency; HSE of the brainstem. Other viral infections of the brainstem; Defects in intrinsic and innate immunity for gene: DBR1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 CLCN7 Ellen McDonagh Source Expert Review Green was added to CLCN7.
Added phenotypes Defects in Intrinsic and Innate Immunity; Osteopetrosis with hypocalcemia, neurologic features for gene: CLCN7
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 C8G Ellen McDonagh Source Expert Review Green was added to C8G.
Added phenotypes Complement Deficiencies; Complement factor 8 defect; Complement component 8 deficiency; Disseminated neisserial infections for gene: C8G
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 C17orf62 Ellen McDonagh Source Expert Review Green was added to C17orf62.
Added phenotypes Autosomal recessive CGD EROS; Congenital defects of phagocyte number or function for gene: C17orf62
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 BRCA2 Ellen McDonagh Source Expert Review Green was added to BRCA2.
Added phenotypes Fanconi anemia, complementation group D1, 605724; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Fanconi Anemia Type D1; Bone marrow failure for gene: BRCA2
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 BRCA1 Ellen McDonagh Source Expert Review Green was added to BRCA1.
Added phenotypes Fanconi Anemia Type S; Fanconi anemia, complementation group S, 617883; normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure for gene: BRCA1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ARHGEF1 Ellen McDonagh Source Expert Review Green was added to ARHGEF1.
Added phenotypes Recurrent infections, bronchiectasis; Immunodeficiency 62, 618459; ARHGEF1 deficiency; Predominantly Antibody Deficiencies for gene: ARHGEF1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 AP3D1 Ellen McDonagh Source Expert Review Green was added to AP3D1.
Added phenotypes neutropenia; Immunodeficient HPS; seizures; Diseases of Immune Dysregulation; Hermansky-Pudlak syndrome with neutropenia; neuordevelopmental delay; albinism; ?Hermansky-Pudlak syndrome 10, 617050; Hermansky-Pudlak syndrome; Oculocutaneous albinism, recurrent infections, seizures, hearing loss and neurodevelopmental delay; Oculocutaneous albinism, severe neutropenia, recurrent infections, seizures, hearing loss and neurodevelopmental delay; HSP10 for gene: AP3D1
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 ALPI Ellen McDonagh Source Expert Review Green was added to ALPI.
Added phenotypes Inflammatory bowel disease; ALPI deficiency; Autoinflammatory Disorders for gene: ALPI
Rating Changed from Red List (low evidence) to Green List (high evidence)
COVID-19 research v0.40 TINF2 Ellen McDonagh Source Expert Review Green was added to TINF2.
Added phenotypes microcephaly, neurodevelopmental delay exudative retinopathy; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay for gene: TINF2
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TERC Ellen McDonagh Source Expert Review Green was added to TERC.
Added phenotypes Dyskeratosis congenita; Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; Dyskeratosis congenita 1; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; Combined immunodeficiencies with associated or syndromic features; Hoyeraal-Hreidarsson syndrome; microcephaly, neurodevelopmental delay for gene: TERC
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TBX1 Ellen McDonagh Source Expert Review Green was added to TBX1.
Added phenotypes Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; DiGeorge syndrome 188400; Di George syndrome; T-B+ SCID; Severe combined immunodeficiency (SCID); Combined immunodeficiencies with associated or syndromic features for gene: TBX1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 SAMD9L Ellen McDonagh Source Expert Review Green was added to SAMD9L.
Added phenotypes Cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction; Combined immunodeficiencies with associated or syndromic features; MDS, neurological features; Bone marrow failure for gene: SAMD9L
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 SAMD9 Ellen McDonagh Source Expert Review Green was added to SAMD9.
Added phenotypes IUGR with gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen; MIRAGE syndrome (Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy); ataxia-thrombocytopenia syndrome; Bone marrow failure; Combined immunodeficiencies with associated or syndromic features for gene: SAMD9
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 PTEN Ellen McDonagh Source Expert Review Green was added to PTEN.
Added phenotypes Recurrent infections, Lymphoproliferation, Autoimmunity; Lymphoproliferation, Autoimmunity; developmental delay; Predominantly Antibody Deficiencies for gene: PTEN
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 PSENEN Ellen McDonagh Source Expert Review Green was added to PSENEN.
Added phenotypes Acne inversa, familial, 2, with or without Dowling-Degos disease 613736; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa for gene: PSENEN
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 NCSTN Ellen McDonagh Source Expert Review Green was added to NCSTN.
Added phenotypes Hidradenitis suppurativa with acne, 142690; Defects in intrinsic and innate immunity; familial hydradenitis suppurativa; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa with acne for gene: NCSTN
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 IRF3 Ellen McDonagh Source Expert Review Green was added to IRF3.
Added phenotypes {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 7}, 616532; Herpes simplex virus 1 encephalitis; Defects in Intrinsic and Innate Immunity for gene: IRF3
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 IL17F Ellen McDonagh Source Expert Review Green was added to IL17F.
Added phenotypes CMC, folliculitis; Candidiasis, familial, 6, 613956; Defects in Intrinsic and Innate Immunity; Chronic mucocutaneous candidiasis (CMC) for gene: IL17F
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TERT Ellen McDonagh Source Expert Review Green was added to TERT.
Added phenotypes Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay for gene: TERT
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 RAC2 Ellen McDonagh Source Expert Review Green was added to RAC2.
Added phenotypes Reticular dysgenesis; poststreptococcal glomerulonephritis; Congenital defects of phagocyte number or function; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Recurrent sinopulmonary infections, selective IgA defiency; urticaria; T-B- SCID; Poor wound healing, leukocytosis for gene: RAC2
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 NLRP1 Ellen McDonagh Source Expert Review Green was added to NLRP1.
Added phenotypes Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammation with arthritis and dyskeratosis; Autoinflammatory Disorders for gene: NLRP1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFHR5 Ellen McDonagh Source Expert Review Green was added to CFHR5.
Added phenotypes Atypical hemolytic-uremic syndrome with anti-factor H antibodies; Atypical hemolytic uremic syndrome susceptibility; Nephropathy due to CFHR5 deficiency, 614809; Complement Deficiencies; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR5
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFHR4 Ellen McDonagh Source Expert Review Green was added to CFHR4.
Added phenotypes Complement Deficiencies; Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR4
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFHR3 Ellen McDonagh Source Expert Review Green was added to CFHR3.
Added phenotypes Complement Deficiencies; Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR3
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFHR1 Ellen McDonagh Source Expert Review Green was added to CFHR1.
Added phenotypes Complement Deficiencies; Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFB Ellen McDonagh Source Expert Review Green was added to CFB.
Added phenotypes Infections with encapsulated organisms; Complement Deficiencies; complement factor B deficiency (AR); Atypical Hemolytic-uremic syndrome; Complement factor B deficiency, 615561; Susceptibility to atypical haemolytic uraemic syndrome 4 (AD) for gene: CFB
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 WDR1 Ellen McDonagh Source Expert Review Green was added to WDR1.
Added phenotypes Mild neutropenia, poor wound healing, severe stomatitis, neutrophil nuclei herniate; Congenital defects of phagocyte number or function for gene: WDR1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 USP18 Ellen McDonagh Source Expert Review Green was added to USP18.
Added phenotypes Pseudo-TORCH syndrome 2, 617397; Autoinflammatory Disorders; TORCH like syndrome for gene: USP18
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFRSF13C Ellen McDonagh Source Expert Review Green was added to TNFRSF13C.
Added phenotypes Immunodeficiency, common variable, 4; Variable clinical expression; Isolated IgG subclass deficiency; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies for gene: TNFRSF13C
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TNFRSF11A Ellen McDonagh Source Expert Review Green was added to TNFRSF11A.
Added phenotypes Osteopetrosis; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity for gene: TNFRSF11A
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 TAPBP Ellen McDonagh Source Expert Review Green was added to TAPBP.
Added phenotypes Bare lymphocyte syndrome, type I 604571; Vasculitis, pyoderma gangrenosum; HLA class I deficiency; Immunodeficiencies affecting cellular and humoral immunity; Vasculitis,pyoderma gangrenosum for gene: TAPBP
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 RHOH Ellen McDonagh Source Expert Review Green was added to RHOH.
Added phenotypes T cell deficiency and various infectious diseases; Combined immunodeficiency; HPV infection, lung granulomas, molluscum contagiosum, lymphoma; Epidermodysplasia verruciformis; Immunodeficiencies affecting cellular and humoral immunity; RhoH deficiency for gene: RHOH
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 POLE Ellen McDonagh Source Expert Review Green was added to POLE.
Added phenotypes Recurrent respiratory infections, meningitis, facial dysmorphism, livido, short stature; Combined immunodeficiencies with associated or syndromic features; FILS syndrome 615139; Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS syndrome) for gene: POLE
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 PMS2 Ellen McDonagh Source Expert Review Green was added to PMS2.
Added phenotypes Recurrent infections, cafe-au-lait spots, lymphoma, colorectal carcinoma, brain tumors; Post-Meiotic Segregation 2 (PMS2) deficiency; Mismatch repair cancer syndrome 276300; Combined immunodeficiencies with associated or syndromic features; CSR defects and Hyper IgM (HIGM) syndromes; Recurrent infections, caf-au-lait spots, lymphoma, colorectal carcinoma, brain tumors for gene: PMS2
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 NOP10 Ellen McDonagh Source Expert Review Green was added to NOP10.
Added phenotypes Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome; Dyskeratosis congenita 1; Dyskeratosis congenita, autosomal recessive 1 224230; Combined immunodeficiencies with associated or syndromic features; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients for gene: NOP10
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 IRF7 Ellen McDonagh Added phenotypes Severe influenza; ?Immunodeficiency 39, 616345; Severe influenza disease; IRF7 deficiency; Defects in Intrinsic and Innate Immunity for gene: IRF7
Publications for gene IRF7 were updated from 26761402; 9315633; 32086639; 25814066; 32048120; 26621750 to 26761402; 9315633; 32086639; 25814066; 32048120; 26621750
COVID-19 research v0.40 IL21 Ellen McDonagh Source Expert Review Green was added to IL21.
Added phenotypes Immunodeficiency, common variable, 11, 615767; Severe early onset colitis, recurrent sinopulmonary infections; Immunodeficiencies affecting cellular and humoral immunity for gene: IL21
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 IGKC Ellen McDonagh Source Expert Review Green was added to IGKC.
Added phenotypes Immunoglobulin chain deficiencies; Kappa light chain deficiency, 614102; Asymptomatic; Predominantly Antibody Deficiencies for gene: IGKC
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 FPR1 Ellen McDonagh Source Expert Review Green was added to FPR1.
Added phenotypes Periodontitis only; Congenital defects of phagocyte number or function; Periodontitis; Localized juvenile peridontitis for gene: FPR1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 FCGR3A Ellen McDonagh Added phenotypes severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV); CD16 deficiency; predisposition to severe viral infection; Immunodeficiency 20, 615707; Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity; Defects in Intrinsic and Innate Immunity; Fc receptor deficiencies for gene: FCGR3A
COVID-19 research v0.40 DNASE1L3 Ellen McDonagh Source Expert Review Green was added to DNASE1L3.
Added phenotypes Systemic lupus erythematosus 16, 614420; Autoinflammatory Disorders; Diseases of Immune Dysregulation; familial early-onset SLE; Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis for gene: DNASE1L3
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CTC1 Ellen McDonagh Source Expert Review Green was added to CTC1.
Added phenotypes Cerebroretinal microangiopathy with calcifications and cysts, 612199; Combined immunodeficiencies with associated or syndromic features; Bone marrow failure; Intrauterine growth retardation, sparse graying hair, dystrophic nails, trilinear bone marrow failure, osteopenia, gastrointestinal hemorrhage due to vascular ectasia, retinal telangiectasia, intracranial calcification, abnormal telomeres for gene: CTC1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CR2 Ellen McDonagh Source Expert Review Green was added to CR2.
Added phenotypes Recurrent infections; Lupus; Isolated IgG subclass deficiency; Immunodeficiency, common variable, 7; Common variable immunodeficiency disorders (CVID); hypogammaglobulinaemia; Predominantly Antibody Deficiencies; Immunodeficiency, common variable, 7, 614699 for gene: CR2
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CFTR Ellen McDonagh Source Expert Review Green was added to CFTR.
Added phenotypes Congenital defects of phagocyte number or function; Respiratory infections, pancreatic insufficiency, elevated sweat chloride; Cystic fibrosis, 219700 for gene: CFTR
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CD8A Ellen McDonagh Source Expert Review Green was added to CD8A.
Added phenotypes Susceptibility to respiratory infections associated with CD8alpha chain mutation; Immunodeficiencies affecting cellular and humoral immunity; CD8 deficiency familial, 608957; Recurrent infections, may be asymptomatic for gene: CD8A
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CD81 Ellen McDonagh Source Expert Review Green was added to CD81.
Added phenotypes CD81 deficiency; Isolated IgG subclass deficiency; Recurrent infections, may have glomerulonephritis; Common variable immunodeficiency disorders (CVID); hypogammaglobulinaemia; Predominantly Antibody Deficiencies; Immunodeficiency, common variable 6, 613496 for gene: CD81
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 CD247 Ellen McDonagh Source Expert Review Green was added to CD247.
Added phenotypes ?Immunodeficiency 25; T-B+ severe combined immunodeficiency due to CD3zeta; Immunodeficiency 25, 610163; Atypical Severe Combined Immunodeficiency (Atypical SCID); Nl NK, no g/d T cells; Immunodeficiencies affecting cellular and humoral immunity; T-B+ SCID; Severe combined immunodeficiency (SCID) for gene: CD247
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 BCL10 Ellen McDonagh Source Expert Review Green was added to BCL10.
Added phenotypes Combined immunodeficiency with B cell, T cell, and fibroblast defects; ?Immunodeficiency 37, 616098; Recurrent bacterial and viral infections, candidiasis, gastroenteritis; Immunodeficiencies affecting cellular and humoral immunity for gene: BCL10
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 AP1S3 Ellen McDonagh Source Expert Review Green was added to AP1S3.
Added phenotypes Pustular psoriasis, 616106; Autoinflammatory Disorders; Pustular psoriasis for gene: AP1S3
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.40 ADAM17 Ellen McDonagh Source Expert Review Green was added to ADAM17.
Added phenotypes IBD-1; ADAM17 deficiency; Inflammatory skin and bowel disease, neonatal, 1; Inflammatory skin and bowel disease, neonatal 1, 614328; Autoinflammatory Disorders; inflammatory skin; Early onset diarrhea and skin lesions for gene: ADAM17
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
COVID-19 research v0.39 FBF1 Catherine Snow reviewed gene: FBF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
COVID-19 research v0.39 IFNAR1 Sarah Leigh gene: IFNAR1 was added
gene: IFNAR1 was added to Viral susceptibility. Sources: Literature
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNAR1 were set to 31270247; 26676772; 20020050
Phenotypes for gene: IFNAR1 were set to IFNAR1 associated adverse reactions to certain live attenuated viral vaccines
Review for gene: IFNAR1 was set to AMBER
Added comment: Hypothesis from Abdelazeem Elhabyan (Tanta University Hospitals): this gene is involved in the interferon-mediated immune response to viruses of those is SARS Coronavirus (2003) which down-regulates the IFNAR1 receptors through its 3a protein. Additionally, Influenzavirus A suppress immune response by downregulation of this gene. It has been also linked to adverse reactions to measles and yellow fever vaccines in healthy individuals.
Sources: Literature
COVID-19 research v0.36 NFKBID Ellen McDonagh gene: NFKBID was added
gene: NFKBID was added to Viral susceptibility. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: NFKBID was set to Unknown
COVID-19 research v0.36 MPI Ellen McDonagh gene: MPI was added
gene: MPI was added to Viral susceptibility. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: MPI was set to Unknown
COVID-19 research v0.36 MASP1 Ellen McDonagh gene: MASP1 was added
gene: MASP1 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: MASP1 was set to Unknown
Phenotypes for gene: MASP1 were set to Mannan-binding lectin serine protease (MASP) deficiency
COVID-19 research v0.36 IL23A Ellen McDonagh gene: IL23A was added
gene: IL23A was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: IL23A was set to Unknown
Phenotypes for gene: IL23A were set to Defects with susceptibility to mycobacterial infection (MSMD)
COVID-19 research v0.36 IL18 Ellen McDonagh gene: IL18 was added
gene: IL18 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: IL18 was set to Unknown
Phenotypes for gene: IL18 were set to Defects with susceptibility to mycobacterial infection (MSMD)
COVID-19 research v0.36 IL17A Ellen McDonagh gene: IL17A was added
gene: IL17A was added to Viral susceptibility. Sources: Expert Review Red,GRID V2.0
Mode of inheritance for gene: IL17A was set to Unknown
Phenotypes for gene: IL17A were set to Arthritis; Immunodeficiency 5
COVID-19 research v0.36 IGHG2 Ellen McDonagh gene: IGHG2 was added
gene: IGHG2 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: IGHG2 was set to Unknown
Phenotypes for gene: IGHG2 were set to Immunoglobulin chain deficiencies
COVID-19 research v0.36 GTF2H5 Ellen McDonagh gene: GTF2H5 was added
gene: GTF2H5 was added to Viral susceptibility. Sources: North West GLH,NHS GMS,London North GLH
Mode of inheritance for gene: GTF2H5 was set to Unknown
COVID-19 research v0.36 FPR3 Ellen McDonagh gene: FPR3 was added
gene: FPR3 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: FPR3 was set to Unknown
Phenotypes for gene: FPR3 were set to Localized juvenile peridontitis
COVID-19 research v0.36 FPR2 Ellen McDonagh gene: FPR2 was added
gene: FPR2 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: FPR2 was set to Unknown
Phenotypes for gene: FPR2 were set to Localized juvenile peridontitis
COVID-19 research v0.36 FCGRT Ellen McDonagh gene: FCGRT was added
gene: FCGRT was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: FCGRT was set to Unknown
Phenotypes for gene: FCGRT were set to Fc receptor deficiencies
COVID-19 research v0.36 FCGR2B Ellen McDonagh gene: FCGR2B was added
gene: FCGR2B was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: FCGR2B was set to Unknown
Phenotypes for gene: FCGR2B were set to Fc receptor deficiencies
COVID-19 research v0.36 FCGR2A Ellen McDonagh Mode of inheritance for gene FCGR2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
Added phenotypes Fc receptor deficiencies for gene: FCGR2A
COVID-19 research v0.36 FCGR1A Ellen McDonagh gene: FCGR1A was added
gene: FCGR1A was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: FCGR1A was set to Unknown
Phenotypes for gene: FCGR1A were set to Fc receptor deficiencies
COVID-19 research v0.36 FBF1 Ellen McDonagh gene: FBF1 was added
gene: FBF1 was added to Viral susceptibility. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: FBF1 was set to Unknown
COVID-19 research v0.36 COLEC11 Ellen McDonagh gene: COLEC11 was added
gene: COLEC11 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: COLEC11 was set to Unknown
Phenotypes for gene: COLEC11 were set to Mannan-binding lectin serine protease (MASP) deficiency
COVID-19 research v0.36 CNBP Ellen McDonagh gene: CNBP was added
gene: CNBP was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: CNBP was set to Unknown
Phenotypes for gene: CNBP were set to Steinert- myotonica dystrophia
COVID-19 research v0.36 CD4 Ellen McDonagh gene: CD4 was added
gene: CD4 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117
Mode of inheritance for gene: CD4 was set to Unknown
Phenotypes for gene: CD4 were set to Selective CD4 cell deficiency
COVID-19 research v0.36 PSMA3 Ellen McDonagh gene: PSMA3 was added
gene: PSMA3 was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,North West GLH,NHS GMS,London North GLH,Expert Review Amber
Mode of inheritance for gene: PSMA3 was set to Unknown
Publications for gene: PSMA3 were set to 26524591
Phenotypes for gene: PSMA3 were set to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
COVID-19 research v0.36 KDM6A Ellen McDonagh gene: KDM6A was added
gene: KDM6A was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM6A were set to 25142838; 25546742; 26411453; 32086639; 15887282; 15523604; 32048120
Phenotypes for gene: KDM6A were set to Combined immunodeficiencies with associated or syndromic features; Kabuki Syndrome 2 due to KDM6A deficiency; Typical facial abnormalities, cleft or high arched palate, skeletal abnormalities, short stature, intellectual disability, congenital heart defects, recurrent infections (otitis media, pneumonia) in 50% of patients. Autoimmunity may be present
COVID-19 research v0.36 XIAP Ellen McDonagh gene: XIAP was added
gene: XIAP was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: XIAP were set to 25943627; 21119115; 17080092; 21173700; 22228567
Phenotypes for gene: XIAP were set to Lymphoproliferative syndrome, X-linked, 2 (XLP2); inflammatory bowel disease; 300635; splenomegaly; Diseases of Immune Dysregulation; X-linked lymphoproliferative syndrome (XLP); haemophagocytic lymphohistiocytosis; Lymphoproliferative syndrome, X-linked, 2; EBV infection, Splenomegaly, lymphoproliferation, HLH, Colitis, IBD, hepatitis, Low iNKT cells, hypogammaglobulinemia
COVID-19 research v0.36 CYBB Ellen McDonagh gene: CYBB was added
gene: CYBB was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CYBB was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CYBB were set to 1710153; 2556453; 17293536
Phenotypes for gene: CYBB were set to Chronic granulomatous disease, X-linked, 306400; Defects with susceptibility to mycobacterial infection (MSMD); Congenital defects of phagocyte number or function; Immunodeficiency 34, mycobacteriosis, X-linked, 300645; Chronic granulomatous disease (CGD); Isolated susceptibility to mycobacteria; Infections, autoinflammatory phenotype, IBD, McLeod phenotype in patients with deletions extending into the contiguous Kell locus; Defects in Intrinsic and Innate Immunity
COVID-19 research v0.36 SH3KBP1 Ellen McDonagh gene: SH3KBP1 was added
gene: SH3KBP1 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: SH3KBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH3KBP1 were set to 32086639; 32048120; 29636373
Phenotypes for gene: SH3KBP1 were set to Predominantly Antibody Deficiencies; Severe bacterial infections; SH3KBP1 (CIN85) deficiency; Immunodeficiency 61, 300310
COVID-19 research v0.36 IRAK1 Ellen McDonagh gene: IRAK1 was added
gene: IRAK1 was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: IRAK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRAK1 were set to 32086639; 32048120; 28069966
Phenotypes for gene: IRAK1 were set to Bacterial infections, X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1; Defects in Intrinsic and Innate Immunity
COVID-19 research v0.36 WAS Ellen McDonagh gene: WAS was added
gene: WAS was added to Viral susceptibility. Sources: Expert Review Green,Combined B and T cell defect v1.12,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WAS were set to 11242115; 16804117
Phenotypes for gene: WAS were set to Wiskott-Aldrich syndrome (WAS); Combined immunodeficiencies with associated or syndromic features; Neutropenia, myeloid maturation arrest, monocytopenia, variable lymphoid anomalies; Congenital neutropenia; X-linked thrombocytopenia; Congenital defects of phagocyte number or function; X-linked thrombocytopenia with mutations in WASP; Thrombocytopenia with small platelets, recurrent bacterial and viral infections, bloody diarrhea, eczema, lymphoma, autoimmune disease, IgA nephropathy, vasculitis; Neutropenia, severe congenital, X-linked, 300299; XL thrombocytopenia is a mild form of WAS, and XL neutropenia is caused by missense mutations in the GTPase binding domain of WASp; Wiskott-Aldrich syndrome
Mode of pathogenicity for gene: WAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 TAZ Ellen McDonagh gene: TAZ was added
gene: TAZ was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TAZ were set to Barth syndrome; 3-methylglutaconic aciduria, type II, 302060; Congenital defects of phagocyte number or function; Cardiomyopathy, myopathy, growth retardation, neutropenia; Cardioskeletal myopathy with neutropenia and abnormal mitochondria
COVID-19 research v0.36 SH2D1A Ellen McDonagh gene: SH2D1A was added
gene: SH2D1A was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH2D1A were set to 10598819; 29670631; 10556288; 11049992; 9774102; 10694488; 9771704
Phenotypes for gene: SH2D1A were set to EBV, HLH, Lymphoproliferation, Aplastic anaemia, Lymphoma. Hypogammaglobulinemia, Absent iNKT cells; Lymphoproliferative syndrome, X-linked, 1 308240; Diseases of Immune Dysregulation; X-linked lymphoproliferative syndrome (XLP); Lymphoproliferative syndrome, X-linked, 1 (XLP1)
COVID-19 research v0.36 POLA1 Ellen McDonagh gene: POLA1 was added
gene: POLA1 was added to Viral susceptibility. Sources: Expert Review Green,North West GLH,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POLA1 were set to 27019227
Phenotypes for gene: POLA1 were set to Hyperpigmentation, characteristic facies, lung and GI involvement; Autoinflammatory Disorders; Pigmentary disorder, reticulate, with systemic manifestations, X-linked 301220; X-linked reticulate pigmentary disorder; x-linked cutaneous amyloidosis with systemic features
COVID-19 research v0.36 MSN Ellen McDonagh Added phenotypes Immunodeficiencies affecting cellular and humoral immunity; Recurrent infections with bacteria, varicella, neutropenia; Immunodeficiency 50, 300988; Combined immunodeficiency for gene: MSN
Publications for gene MSN were updated from to 29556235; 27405666
COVID-19 research v0.36 MAGT1 Ellen McDonagh gene: MAGT1 was added
gene: MAGT1 was added to Viral susceptibility. Sources: Expert Review Green,Combined B and T cell defect v1.12,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 21796205; 25504528; 25205404; 24550228; 23846901; 27095930; 23871722; 21983175; 25956530
Phenotypes for gene: MAGT1 were set to Chronic active EBV, lymphoproliferation, combined immunodeficiency, impaired t cell function; Combined immunodeficiency; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia; Immunodeficiency, X-linked, with magnesium defect; Diseases of Immune Dysregulation; Epstein-Barr virus infection and neoplasia (XMEN); EBV infection, lymphoma, viral infections, respiratory and GI infections; XMEN syndrome
COVID-19 research v0.36 IL2RG Ellen McDonagh gene: IL2RG was added
gene: IL2RG was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,SCID v1.6,IUIS Classification February 2018
Mode of inheritance for gene: IL2RG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: IL2RG were set to Severe combined immunodeficiency, X-linked; Combined immunodeficiency, X-linked, moderate; Severe Combined Immune Deficiency; Atypical Severe Combined Immunodeficiency (Atypical SCID); Immunodeficiencies affecting cellular and humoral immunity; SCID; Severe combined immunodeficiency, X-linked, 300400; T-B+ SCID; SCID (x-linked); Omenn syndrome; Severe combined immunodeficiency (SCID); Low NK
COVID-19 research v0.36 IKBKG Ellen McDonagh gene: IKBKG was added
gene: IKBKG was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: IKBKG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IKBKG were set to 11047757
Phenotypes for gene: IKBKG were set to Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Immunodeficiency 33, 300636; Invasive pneumococcal disease, recurrent isolated, 2,300640; Defects of TLR/NFkappa-B signalling; Anhidrotic ectodermal dysplasia (in some), various infections (bacteria, mycobacteria, viruses and fungi), colitis, conical teeth, variable defects of skin, hair and teeth, monocyte dysfunction; Ectodermal dysplasia, hypohidrotic, with immune deficiency 300291; Combined immunodeficiencies with associated or syndromic features; Immunodeficiency, isolated, 300584
COVID-19 research v0.36 GATA1 Ellen McDonagh gene: GATA1 was added
gene: GATA1 was added to Viral susceptibility. Sources: Expert Review Green,North West GLH,Congenital neutropaenia v1.22,NHS GMS,London North GLH
Mode of inheritance for gene: GATA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GATA1 were set to 16783379; 22706301
Phenotypes for gene: GATA1 were set to neutropenia; dyserythropoietic anaemia; thrombocytopenia; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, 300835
COVID-19 research v0.36 G6PD Ellen McDonagh Mode of inheritance for gene G6PD was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added phenotypes Infections; haemolytic anaemia; Congenital defects of phagocyte number or function; chronic granulomatous disease-like susceptibility to infection; Glucose-6-phosphate dehydrogenase deficiency (G6PD) for gene: G6PD
Publications for gene G6PD were updated from 26694452; 18269318; 27458052; 27914961 to 18269318; 3681550; 26694452; 12130518; 27914961; 27458052
COVID-19 research v0.36 FOXP3 Ellen McDonagh gene: FOXP3 was added
gene: FOXP3 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 17635943; 11120765; 11295725; 16741580; 14671208
Phenotypes for gene: FOXP3 were set to FOXP3 deficiency (IPEX); Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome; Diseases of Immune Dysregulation; Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790; IPEX; Autoimmune enteropathy, early onset diabetes, hyroiditis hemolytic anemia, thrombocytopenia, eczema, elevated IgE, IgA
COVID-19 research v0.36 DKC1 Ellen McDonagh gene: DKC1 was added
gene: DKC1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DKC1 were set to 9590285; 10583221; 10217077; 9590276
Phenotypes for gene: DKC1 were set to Dyskeratosis congenita, X-linked 305000; Severe phenotype with DD and cerebellar hypoplasia; Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; Combined immunodeficiencies with associated or syndromic features; Hoyeraal-Hreidarsson syndrome; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, recurrent infections
COVID-19 research v0.36 CFP Ellen McDonagh gene: CFP was added
gene: CFP was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CFP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CFP were set to 22229731; 10909851; 8530058; 7151327; 6903190
Phenotypes for gene: CFP were set to Neisserial infections; Complement Deficiencies; Properdin deficiency; Properdin P factor complement deficiency (PFC)
COVID-19 research v0.36 CD40LG Ellen McDonagh gene: CD40LG was added
gene: CD40LG was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CD40LG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CD40LG were set to 7678782; 7586644; 11875495; 20301576; 7882172; 17146684; 8094231; 7679206; 7679801
Phenotypes for gene: CD40LG were set to Hyper-IGM immunodeficiency, X-linked; HIGM; Hyper-IGM syndrome; Hyper-IgM syndrome type 1; Neutropenia, thrombocytopenia, hemolytic anemia, opportunistic infections, biliary tract and liver disease, Cryptosporidium infections; XHIM; Immunodeficiency, X-linked, with hyper-IgM; Immunodeficiencies affecting cellular and humoral immunity; Hyper-IgM syndrome due to CD40 ligand deficiency; Hyper-IgM syndrome due to CD40L deficiency; IHIS; HIGM1; IMD3; CSR defects and Hyper IgM (HIGM) syndromes; Immunodeficiency 3; CD40 ligand deficiency
COVID-19 research v0.36 BTK Ellen McDonagh gene: BTK was added
gene: BTK was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: BTK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BTK were set to 20301626
Phenotypes for gene: BTK were set to Agammaglobulinemia, X-linked 1, 300755; Agammaglobulinemia, X-linked; Agammaglobulinemia, X-linked 1 (XLA); Agammaglobulinemia; Severe bacterial infections, normal numbers of pro-B cells; agammaglobulinaemia; Agammaglobulinemia and isolated hormone deficiency, 307200; Agammaglobulinemia and isolated hormone deficiency; Predominantly Antibody Deficiencies; CVID
COVID-19 research v0.36 ATP6AP1 Ellen McDonagh gene: ATP6AP1 was added
gene: ATP6AP1 was added to Viral susceptibility. Sources: Expert Review Green,North West GLH,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: ATP6AP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP1 were set to 27231034
Phenotypes for gene: ATP6AP1 were set to Immunodeficiency and hepatopathy with or without neurologic features; Hepatopathy, leukopenia, low copper; Predominantly Antibody Deficiencies; Immunodeficiency 47, 300972
COVID-19 research v0.36 STAT5A Ellen McDonagh gene: STAT5A was added
gene: STAT5A was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117,GOSH PID v.8.0
Mode of inheritance for gene: STAT5A was set to Unknown
Publications for gene: STAT5A were set to 16418296
Phenotypes for gene: STAT5A were set to Defects with susceptibility to mycobacterial infection (MSMD); Combined immunodeficiency
COVID-19 research v0.36 SART3 Ellen McDonagh gene: SART3 was added
gene: SART3 was added to Viral susceptibility. Sources: Expert Review Red,GRID V2.0
Mode of inheritance for gene: SART3 was set to Unknown
Phenotypes for gene: SART3 were set to Porokeratosis
COVID-19 research v0.36 ITGAM Ellen McDonagh gene: ITGAM was added
gene: ITGAM was added to Viral susceptibility. Sources: Expert Review Red,Victorian Clinical Genetics Services,GRID V2.0
Mode of inheritance for gene: ITGAM was set to Unknown
Phenotypes for gene: ITGAM were set to Systemic lupus erythematous
COVID-19 research v0.36 FCGR3B Ellen McDonagh gene: FCGR3B was added
gene: FCGR3B was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117,GRID V2.0,Congenital neutropaenia v1.22
Mode of inheritance for gene: FCGR3B was set to Unknown
Publications for gene: FCGR3B were set to 1978690
Phenotypes for gene: FCGR3B were set to Neutropenia,alloimmuneneonatal; Neutropenia, autoimmune neonatal; Neutropenia, alloimmune neonatal; Fc receptor deficiencies
COVID-19 research v0.36 ERCC2 Ellen McDonagh gene: ERCC2 was added
gene: ERCC2 was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,North West GLH,Other,NHS GMS,London North GLH,Expert Review Red
Mode of inheritance for gene: ERCC2 was set to Unknown
Publications for gene: ERCC2 were set to 11737070
Phenotypes for gene: ERCC2 were set to Combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD); CD4 + lymphopenia
COVID-19 research v0.36 ELF4 Ellen McDonagh gene: ELF4 was added
gene: ELF4 was added to Viral susceptibility. Sources: Expert Review Red,A- or hypo-gammaglobulinaemia v1.25
Mode of inheritance for gene: ELF4 was set to Unknown
Publications for gene: ELF4 were set to 16264330
Phenotypes for gene: ELF4 were set to X-linked hypogammaglobulinemia with isolated growth hormone deficiency
COVID-19 research v0.36 KRAS Ellen McDonagh gene: KRAS was added
gene: KRAS was added to Viral susceptibility. Sources: GRID V2.0,ESID Registry 20171117,Expert Review Amber
Mode of inheritance for gene: KRAS was set to Unknown
Publications for gene: KRAS were set to 21079152; 21063026
Phenotypes for gene: KRAS were set to RAS associated lymphoproliferative disease, 614470; RALD
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 NRAS Ellen McDonagh gene: NRAS was added
gene: NRAS was added to Viral susceptibility. Sources: ESID Registry 20171117,North West GLH,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,Expert Review Amber
Mode of inheritance for gene: NRAS was set to Unknown
Publications for gene: NRAS were set to 21079152; 5896945; 17517660; 29141318
Phenotypes for gene: NRAS were set to Ras associated lymphoproliferative disease (RALD); Autoimmune lymphoproliferative syndrome type IV; RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic 614470
COVID-19 research v0.36 LRRC8A Ellen McDonagh gene: LRRC8A was added
gene: LRRC8A was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117,A- or hypo-gammaglobulinaemia v1.25
Mode of inheritance for gene: LRRC8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LRRC8A were set to Agammaglobulinemia 5, 613506; Agammaglobulinemia
COVID-19 research v0.36 STAT3 Ellen McDonagh gene: STAT3 was added
gene: STAT3 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 17676033; 17881745; 25038750; 25359994
Phenotypes for gene: STAT3 were set to Hyper-IgE recurrent infection syndrome 147060; Hyper IgE syndrome (HIES); Diseases of Immune Dysregulation; Early-onset multi-organ autoimmune disease; Autoimmune disease, multisystem, infantile-onset, 1 615952; Combined immunodeficiencies with associated or syndromic features; Autoimmune disease, multisystem, infantile-onset
Mode of pathogenicity for gene: STAT3 was set to Other - please provide details in the comments
COVID-19 research v0.36 POMP Ellen McDonagh gene: POMP was added
gene: POMP was added to Viral susceptibility. Sources: North West GLH,Expert Review Green,NHS GMS,London North GLH
Mode of inheritance for gene: POMP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POMP were set to 29805043; 26524591
Phenotypes for gene: POMP were set to Proteasome-associated autoinflammatory syndrome 2, 618048; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); combined immunodeficiency with autoinflammation
COVID-19 research v0.36 PIK3CD Ellen McDonagh gene: PIK3CD was added
gene: PIK3CD was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: PIK3CD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CD were set to 24165795; 24136356; 29226301
Phenotypes for gene: PIK3CD were set to Combined immunodeficiency; Activated PI3K-delta syndrome (APDS); Unclassified antibody deficiency; decreased or absent pro-B cells, EBV; Predominantly Antibody Deficiencies; sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia; Severe bacterial infections; Immunodeficiency 14,615513
Mode of pathogenicity for gene: PIK3CD was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 IKZF1 Ellen McDonagh gene: IKZF1 was added
gene: IKZF1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF1 were set to 29889099; 21548011; 26981933
Phenotypes for gene: IKZF1 were set to Immunodeficiency, common variable, 13, 616873; IKAROS deficiency; Immunodeficiency, common variable 13; Predominantly Antibody Deficiencies; Recurrent sinopulmonary infections
COVID-19 research v0.36 GFI1 Ellen McDonagh gene: GFI1 was added
gene: GFI1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: GFI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GFI1 were set to Neutropenia, severe congenital 2; Congenital neutropenia; Severe congenital 2, autosomal dominant, 613107; Congenital defects of phagocyte number or function; Neutropenia, nonimmune chronic idiopathic, of adults, 607847; Severe congenital neutropenia; B/T lymphopenia; Chronic non-immune neutropenia of adults
COVID-19 research v0.36 F12 Ellen McDonagh gene: F12 was added
gene: F12 was added to Viral susceptibility. Sources: Expert Review Green,Victorian Clinical Genetics Services,North West GLH,GRID V2.0,NHS GMS,London North GLH
Mode of inheritance for gene: F12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: F12 were set to 17186468; 16638441; 19178938
Phenotypes for gene: F12 were set to hereditary angioedema; Angioedema, Hereditary, Type III
Mode of pathogenicity for gene: F12 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 CTLA4 Ellen McDonagh gene: CTLA4 was added
gene: CTLA4 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 25213377; 25329329
Phenotypes for gene: CTLA4 were set to Autoimmune lymphoproliferative syndrome, type V; interstitual lung disease; autoimmunity; lymphadenopathy; T cell lymphopenia; Combined immunodeficiency; Immune dysregulation; a broad range of autoimmune phenomena have been described along with polyclonal lymphocytic infiltrates. Susceptibility to infection and hypogammaglobulinaemia are not usually present in isolation; Diseases of Immune Dysregulation; Early-onset multi-organ autoimmune disease; Autoimmune lymphoproliferative syndrome, type V 616100; hypogammaglobulinaemia; enteropathy; Autoimmune cytopenias, enteropathy, interstitial lung disease, extra-lymphoid lymphocytic infiltration recurrent infections; CVID
COVID-19 research v0.36 CARD14 Ellen McDonagh gene: CARD14 was added
gene: CARD14 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CARD14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CARD14 were set to 23648549; 23067081; 22703878; 29689250; 29980436; 29704870; 23711932; 22521418; 30248356
Phenotypes for gene: CARD14 were set to Other autoinflammatory diseases with known genetic defect; Psoriasis 2, 602723; Autoinflammatory Disorders; Pityriasis rubra pilaris,173200; immune dysregulation; CARD14 mediated psoriasis; Psoriasis
COVID-19 research v0.36 ISCA-37446-Loss Ellen McDonagh Region: ISCA-37446-Loss was added
Region: ISCA-37446-Loss was added to Viral susceptibility. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37446-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37446-Loss were set to 188400; clefting; Velocardiofacial syndrome; neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells; cardiac malformations; Hearing deficits; DiGeorge syndrome; micrognathia
COVID-19 research v0.36 ISCA-37433-Loss Ellen McDonagh Region: ISCA-37433-Loss was added
Region: ISCA-37433-Loss was added to Viral susceptibility. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37433-Loss were set to 20301696; 15889418; 15545748
Phenotypes for Region: ISCA-37433-Loss were set to diaphragmatic hernia; facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay; 192430; 188400; 22q11.2 deletion syndrome; renal anomalies; cleft palate, polydactyly; congenital heart disease; Learning difficulties; Velocardiofacial syndrome; polyhydramnios; DiGeorge syndrome; immune deficiency
COVID-19 research v0.36 UNC119 Ellen McDonagh gene: UNC119 was added
gene: UNC119 was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117,GRID V2.0
Mode of inheritance for gene: UNC119 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UNC119 were set to 22184408
Phenotypes for gene: UNC119 were set to Immunodeficiency 13 615518; Combined immunodeficiency; Immunodeficiency 13/ UNC119 deficiency
COVID-19 research v0.36 TRAF3 Ellen McDonagh Mode of inheritance for gene TRAF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Herpetic encephalitis (HSE); Herpes simplex virus 1 encephalitis; Defects in Intrinsic and Innate Immunity; Defects in intrinsic and innate immunity; {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849; Herpes simplex encephalitis, susceptibility to, 3 for gene: TRAF3
Publications for gene TRAF3 were updated from to 24378539; 20832341; 32086639; 32048120; 11296228
COVID-19 research v0.36 TOP2B Ellen McDonagh gene: TOP2B was added
gene: TOP2B was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TOP2B were set to 31409799; 32086639; 32048120
Phenotypes for gene: TOP2B were set to Recurrent infections, facial dysmorphism, limb anomalies; Hoffman syndrome/TOP2B deficiency; Predominantly Antibody Deficiencies
COVID-19 research v0.36 TNFSF12 Ellen McDonagh gene: TNFSF12 was added
gene: TNFSF12 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: TNFSF12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFSF12 were set to 23493554; 32086639; 32048120
Phenotypes for gene: TNFSF12 were set to Immunodeficiency, common variable with lack of anti-pneumococcal antibody; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Pneumonia, bacterial infections, warts, thrombocytopenia. neutropenia; Pneumonia, bacterial infections, warts, thrombocytopenia
COVID-19 research v0.36 THBD Ellen McDonagh gene: THBD was added
gene: THBD was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: THBD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: THBD were set to 32086639; 32048120
Phenotypes for gene: THBD were set to Complement Deficiencies; Thrombomodulin deficiency; Hemolytic uremic syndrome, atypical, susceptibility to, 6; Atypical hemolytic-uremic syndrome
COVID-19 research v0.36 TGFBR2 Ellen McDonagh gene: TGFBR2 was added
gene: TGFBR2 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TGFBR2 were set to 32086639; 32048120; 29392890
Phenotypes for gene: TGFBR2 were set to Recurrent respiratory infections, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms; Combined immunodeficiencies with associated or syndromic features; ALPS-FAS
COVID-19 research v0.36 TGFBR1 Ellen McDonagh gene: TGFBR1 was added
gene: TGFBR1 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TGFBR1 were set to 32086639; 32048120; 29392890
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome 1, 609192; Loeys Dietz syndrome due to TGFBR1 deficiency; Combined immunodeficiencies with associated or syndromic features; Recurrent respiratory infectons, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms
COVID-19 research v0.36 SRP54 Ellen McDonagh gene: SRP54 was added
gene: SRP54 was added to Viral susceptibility. Sources: IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: SRP54 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRP54 were set to 32086639; 28972538; 29914977; 32048120
Phenotypes for gene: SRP54 were set to Schwachman Diamond features; Congenital defects of phagocyte number or function
COVID-19 research v0.36 SNORA31 Ellen McDonagh gene: SNORA31 was added
gene: SNORA31 was added to Viral susceptibility. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Herpes simplex encephalitis
COVID-19 research v0.36 SH3BP2 Ellen McDonagh gene: SH3BP2 was added
gene: SH3BP2 was added to Viral susceptibility. Sources: ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: SH3BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SH3BP2 were set to 22640988; 28914985; 29669173; 11381256; 32086639; 32048120
Phenotypes for gene: SH3BP2 were set to Other autoinflammatory diseases with known genetic defect; Autoinflammatory Disorders; Cherubism 118400; Bone degeneration in jaws
COVID-19 research v0.36 SEMA3E Ellen McDonagh gene: SEMA3E was added
gene: SEMA3E was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: SEMA3E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEMA3E were set to 21055784; 32086639; 1735828; 12144540; 32048120
Phenotypes for gene: SEMA3E were set to CHARGE syndrome; immune-mediated cerebellar ataxia; Coloboma, heart anomaly, choanal atresia, intellectual retardation, genital and ear anomalies, CNS malformation, some are SCID-like and have low TRECs; Charge syndrome 214800; Combined immunodeficiencies with associated or syndromic features
COVID-19 research v0.36 SEC61A1 Ellen McDonagh gene: SEC61A1 was added
gene: SEC61A1 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEC61A1 were set to 28782633; 32086639; 32048120
Phenotypes for gene: SEC61A1 were set to Severe recurrent respiratory tract infections; Predominantly Antibody Deficiencies; Hyperuricemic nephropathy, familial juvenile, 4, 617056; SEC61A1 deficiency
COVID-19 research v0.36 SAMD3 Ellen McDonagh gene: SAMD3 was added
gene: SAMD3 was added to Viral susceptibility. Sources: Expert Review Red,NHS GMS,London North GLH
Mode of inheritance for gene: SAMD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SAMD3 were set to HLH, abnormal GRA
COVID-19 research v0.36 RET Ellen McDonagh gene: RET was added
gene: RET was added to Viral susceptibility. Sources: North West GLH,NHS GMS,GOSH PID v.8.0,London North GLH,Expert Review Red
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RET were set to 12086152; 9497256
Phenotypes for gene: RET were set to Central hypoventilation syndrome, congenital 209880
COVID-19 research v0.36 RELA Ellen McDonagh gene: RELA was added
gene: RELA was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELA were set to 28600438; 32086639; 32048120; 29305315
Phenotypes for gene: RELA were set to RelA haplosufficiency; Mucosal ulceration, impaired NFkB activation; Mucocutaneous ulceration, chronic, 618287; Immunodeficiencies affecting cellular and humoral immunity
COVID-19 research v0.36 RANBP2 Ellen McDonagh gene: RANBP2 was added
gene: RANBP2 was added to Viral susceptibility. Sources: North West GLH,NHS GMS,London North GLH,IUIS Classification December 2019,IUIS Classification February 2018
Mode of inheritance for gene: RANBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RANBP2 were set to 32086639; 32048120
Phenotypes for gene: RANBP2 were set to Fever induces acute encephalopathy; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity
COVID-19 research v0.36 PTPN22 Ellen McDonagh gene: PTPN22 was added
gene: PTPN22 was added to Viral susceptibility. Sources: North West GLH,Expert Review Red,NHS GMS,London North GLH
Mode of inheritance for gene: PTPN22 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PTPN22 were set to Lupus susceptibility; {Systemic lupus erythematosus susceptibility to}
COVID-19 research v0.36 PSEN1 Ellen McDonagh gene: PSEN1 was added
gene: PSEN1 was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSEN1 were set to 20929727
Phenotypes for gene: PSEN1 were set to Hidradenitis suppurative with cutaneous hyperpigmentation; Acne inversa, familial, 3 613737; Defects in Intrinsic and Innate Immunity
COVID-19 research v0.36 OAS1 Ellen McDonagh gene: OAS1 was added
gene: OAS1 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OAS1 were set to 32086639; 29455859; 32048120
Phenotypes for gene: OAS1 were set to OAS1 GOF; Autoinflammatory Disorders; Pulmonary alveolar proteinosis, skin rash
COVID-19 research v0.36 NFE2L2 Ellen McDonagh gene: NFE2L2 was added
gene: NFE2L2 was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFE2L2 were set to 32086639; 32048120; 29018201
Phenotypes for gene: NFE2L2 were set to Recurrent respiratory and skin infections, growth retardation, , developmental delay; increased expression of stress response genes; Immunodeficiency, developmental delay, and hypohomocysteinemia, 617744; white matter cerebral lesions, increased level of homocysteine; Combined immunodeficiencies with associated or syndromic features; NFE2L2 GOF
COVID-19 research v0.36 NFAT5 Ellen McDonagh gene: NFAT5 was added
gene: NFAT5 was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: NFAT5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFAT5 were set to 32086639; 32048120
Phenotypes for gene: NFAT5 were set to NFAT5 haploinsufficieny; IBD, recurrent sinopulmonary infections; Diseases of Immune Dysregulation
COVID-19 research v0.36 LYZ Ellen McDonagh gene: LYZ was added
gene: LYZ was added to Viral susceptibility. Sources: Expert Review Red,NHS GMS,London North GLH
Mode of inheritance for gene: LYZ was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LYZ were set to Amyloidosis, renal, 105200
COVID-19 research v0.36 KMT2D Ellen McDonagh gene: KMT2D was added
gene: KMT2D was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2D were set to 25142838; 26411453; 32086639; 15887282; 15523604; 32048120
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, 147920; Combined immunodeficiencies with associated or syndromic features; Typical facial abnormalities, cleft or high arched palate, skeletal abnormalities, short stature, intellectual disability, congenital heart defects, recurrent infections (otitis media, pneumonia) in 50% of patients. Autoimmunity may be present
COVID-19 research v0.36 KMT2A Ellen McDonagh gene: KMT2A was added
gene: KMT2A was added to Viral susceptibility. Sources: Expert Review Red,ESID Registry 20171117,IUIS Classification December 2019
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2A were set to 32086639; 32048120; 27320412
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome with Congenital immunodeficiency; Combined immunodeficiencies with associated or syndromic features; Unclassified antibody deficiency; Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability
COVID-19 research v0.36 JAK1 Ellen McDonagh gene: JAK1 was added
gene: JAK1 was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JAK1 were set to 28111307; 32086639; 32048120
Phenotypes for gene: JAK1 were set to Hypereosinophilic syndrome; HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections; Diseases of Immune Dysregulation; Susceptibility to mycobacteria and viruses, urothelial carcinoma; Defects in Intrinsic and Innate Immunity; HSM, eosinophilic enteritis, thyroid disease, poor growth, viral infections
Mode of pathogenicity for gene: JAK1 was set to Other - please provide details in the comments
COVID-19 research v0.36 IRF2BP2 Ellen McDonagh gene: IRF2BP2 was added
gene: IRF2BP2 was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BP2 were set to 27016798; 32086639; 32048120
Phenotypes for gene: IRF2BP2 were set to Recurrent infections, possible autoimmunity and inflammatory disease; Predominantly Antibody Deficiencies; CVID
COVID-19 research v0.36 IL31RA Ellen McDonagh gene: IL31RA was added
gene: IL31RA was added to Viral susceptibility. Sources: Expert Review Red,NHS GMS,London North GLH
Mode of inheritance for gene: IL31RA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: IL31RA were set to ?Amyloidosis, primary localized cutaneous 2, 613955
COVID-19 research v0.36 ERBIN Ellen McDonagh gene: ERBIN was added
gene: ERBIN was added to Viral susceptibility. Sources: IUIS Classification December 2019
Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ERBIN were set to 28126831; 32086639; 32048120
Phenotypes for gene: ERBIN were set to ERBIN deficiency; Combined immunodeficiencies with associated or syndromic features; Recurrent respiratory infections, susceptibility to S. aureus, eczema, hyperextensible joints, scoliosis, arterial dilatation in some
COVID-19 research v0.36 BCL11B Ellen McDonagh gene: BCL11B was added
gene: BCL11B was added to Viral susceptibility. Sources: Expert Review Red,IUIS Classification February 2018,IUIS Classification December 2019
Mode of inheritance for gene: BCL11B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BCL11B were set to 29296816; 32086639; 32048120; 27959755
Phenotypes for gene: BCL11B were set to Combined immunodeficiencies with associated or syndromic features; leaky SCID; ?Immunodeficiency 49, 617237; Immunodeficiencies affecting cellular and humoral immunity; Congenital abnormalities, neonatal teeth, dysmorphic facies, absent corpus callosum, neurocognitive deficits
COVID-19 research v0.36 APOL1 Ellen McDonagh gene: APOL1 was added
gene: APOL1 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: APOL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: APOL1 were set to 16720107; 15894515; 25100047; 28827791; 32086639; 29470556; 29077717; 32048120; 28537557
Phenotypes for gene: APOL1 were set to Defects in Intrinsic and Innate Immunity; Trypanosomiasis, susceptibility to; Trypanosomias; Trypanosomiasis
COVID-19 research v0.36 ACTB Ellen McDonagh gene: ACTB was added
gene: ACTB was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTB were set to 32086639; 32048120; 10411937
Phenotypes for gene: ACTB were set to Congenital defects of phagocyte number or function; neutrophil dysfunction; Mental retardation, short stature; Actin beta deficiency (ACTB); Phagocytic disorder; Poor neutrophil chemotaxis, oxidative burst and actin remodeling. Thrombocytopenia; Baraitser-Winter syndrome 1, 243310
COVID-19 research v0.36 TINF2 Ellen McDonagh gene: TINF2 was added
gene: TINF2 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TINF2 were set to 18252230; 21199492; 21477109; 18979121; 27033759; 18669893; 29742735
Phenotypes for gene: TINF2 were set to microcephaly, neurodevelopmental delay exudative retinopathy; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay
COVID-19 research v0.36 TERC Ellen McDonagh gene: TERC was added
gene: TERC was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: TERC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TERC were set to 16332973; 32086639; 12525685; 32048120; 11574891
Phenotypes for gene: TERC were set to Dyskeratosis congenita; Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; Dyskeratosis congenita 1; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; Combined immunodeficiencies with associated or syndromic features; Hoyeraal-Hreidarsson syndrome; microcephaly, neurodevelopmental delay
COVID-19 research v0.36 TBX1 Ellen McDonagh gene: TBX1 was added
gene: TBX1 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,SCID v1.6,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: TBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TBX1 were set to 11242110; 24198816; 14585638; 32086639; 32048120
Phenotypes for gene: TBX1 were set to Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; DiGeorge syndrome 188400; Di George syndrome; T-B+ SCID; Severe combined immunodeficiency (SCID); Combined immunodeficiencies with associated or syndromic features
COVID-19 research v0.36 SAMD9L Ellen McDonagh gene: SAMD9L was added
gene: SAMD9L was added to Viral susceptibility. Sources: North West GLH,NHS GMS,London North GLH,IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: SAMD9L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9L were set to 32086639; 32048120; 28202457
Phenotypes for gene: SAMD9L were set to Cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction; Combined immunodeficiencies with associated or syndromic features; MDS, neurological features; Bone marrow failure
COVID-19 research v0.36 SAMD9 Ellen McDonagh gene: SAMD9 was added
gene: SAMD9 was added to Viral susceptibility. Sources: IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9 were set to 29175836; 32086639; 29266745; 29535429; 28487541; 32048120
Phenotypes for gene: SAMD9 were set to IUGR with gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen; MIRAGE syndrome (Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy); ataxia-thrombocytopenia syndrome; Bone marrow failure; Combined immunodeficiencies with associated or syndromic features
COVID-19 research v0.36 PTEN Ellen McDonagh gene: PTEN was added
gene: PTEN was added to Viral susceptibility. Sources: North West GLH,NHS GMS,London North GLH,IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PTEN were set to 32086639; 27426521; 32048120
Phenotypes for gene: PTEN were set to Recurrent infections, Lymphoproliferation, Autoimmunity; Lymphoproliferation, Autoimmunity; developmental delay; Predominantly Antibody Deficiencies
COVID-19 research v0.36 PSENEN Ellen McDonagh gene: PSENEN was added
gene: PSENEN was added to Viral susceptibility. Sources: IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: PSENEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSENEN were set to 23439959; 28601418; 28287404; 23020871; 20929727; 32086639; 21412258; 27900998; 32048120; 28922471
Phenotypes for gene: PSENEN were set to Acne inversa, familial, 2, with or without Dowling-Degos disease 613736; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa
COVID-19 research v0.36 NCSTN Ellen McDonagh gene: NCSTN was added
gene: NCSTN was added to Viral susceptibility. Sources: IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: NCSTN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NCSTN were set to 20929727; 32086639; 32048120; 21412258
Phenotypes for gene: NCSTN were set to Hidradenitis suppurativa with acne, 142690; Defects in intrinsic and innate immunity; familial hydradenitis suppurativa; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa with acne
COVID-19 research v0.36 IRF3 Ellen McDonagh Mode of inheritance for gene IRF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 7}, 616532; Herpes simplex virus 1 encephalitis; Defects in Intrinsic and Innate Immunity for gene: IRF3
Publications for gene IRF3 were updated from to 32086639; 26513235; 32048120; 26216125
COVID-19 research v0.36 IL17F Ellen McDonagh gene: IL17F was added
gene: IL17F was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: IL17F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IL17F were set to 32086639; 32048120; 21350122
Phenotypes for gene: IL17F were set to CMC, folliculitis; Candidiasis, familial, 6, 613956; Defects in Intrinsic and Innate Immunity; Chronic mucocutaneous candidiasis (CMC)
COVID-19 research v0.36 TNFRSF1A Ellen McDonagh gene: TNFRSF1A was added
gene: TNFRSF1A was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: TNFRSF1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFRSF1A were set to 11175303; 10199409; 10902757; 17360963
Phenotypes for gene: TNFRSF1A were set to Periodic fever, familial 142680; TNF-receptor associated periodic fever syndrome (TRAPS); Recurrent fever, serositis, rash, and ocular or joint inflammation; Autoinflammatory Disorders
COVID-19 research v0.36 TNFAIP3 Ellen McDonagh gene: TNFAIP3 was added
gene: TNFAIP3 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: TNFAIP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFAIP3 were set to 27845235; 29572183; 26642243; 28659290; 29317407
Phenotypes for gene: TNFAIP3 were set to A20 deficiency; Autoimmune lymphoproliferative syndrome; Autoinflammatory Disorders; Autoinflammatory syndrome, familial, Behcet-like, 616744; Arthralgia, mucosal ulcers, ocular inflammation
COVID-19 research v0.36 TMEM173 Ellen McDonagh Mode of pathogenicity for gene TMEM173 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Autoinflammatory Disorders; Type 1 interferonopathies; Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC, FCL; STING-associated vasculopathy, infantile-onset 615934 for gene: TMEM173
Publications for gene TMEM173 were updated from 25029335; 25401470; 30705050; 29976662; 29491158; 29425920 to 29425920; 29976662; 29491158; 25029335; 25401470; 30705050
COVID-19 research v0.36 TCF3 Ellen McDonagh gene: TCF3 was added
gene: TCF3 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,NHS GMS,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: TCF3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TCF3 were set to 29114388; 28532655; 24216514
Phenotypes for gene: TCF3 were set to Agammaglobulinemia; Recurrent bacterial infections; Agammaglobulinemia 8, autosomal dominant, 616941; Primary immunodeficiency; Predominantly Antibody Deficiencies
Mode of pathogenicity for gene: TCF3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 TBK1 Ellen McDonagh Mode of inheritance for gene TBK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Herpetic encephalitis (HSE); Herpes simplex virus 1 encephalitis; {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900; Herpes simplex encephalitis, susceptibility to; Defects in Intrinsic and Innate Immunity for gene: TBK1
Publications for gene TBK1 were updated from to 22851595; 26513235
COVID-19 research v0.36 RPSA Ellen McDonagh gene: RPSA was added
gene: RPSA was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: RPSA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPSA were set to 22560297; 23579497
Phenotypes for gene: RPSA were set to Isolated congential asplenia 271400; Bacteremia (encapsulated bacteria); Defects in Intrinsic and Innate Immunity
COVID-19 research v0.36 PSTPIP1 Ellen McDonagh gene: PSTPIP1 was added
gene: PSTPIP1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSTPIP1 were set to 28628471; 28960754; 29575118; 26025129; 28251506
Phenotypes for gene: PSTPIP1 were set to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne 604416; Destructive arthritis, inflammatory skin rash, myositis; Hyperzincaemia hypercalprotectinaemia; Autoinflammatory Disorders; Proline/serine/threonine phosphatase-interacting protein 1 deficiency (PSTPIP1); PAPA syndrome
Mode of pathogenicity for gene: PSTPIP1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 PLCG2 Ellen McDonagh gene: PLCG2 was added
gene: PLCG2 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: PLCG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLCG2 were set to 29538758; 23000145; 22236196
Phenotypes for gene: PLCG2 were set to Other autoinflammatory diseases with known genetic defect; Cold urticaria hypogammaglobulinemia, autoinflammation; Familial cold autoinflammatory syndrome 3 614468; Familial cold autoinflammatory syndrome 3; Autoinflammatory Disorders; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory; Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878
Mode of pathogenicity for gene: PLCG2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 NOD2 Ellen McDonagh gene: NOD2 was added
gene: NOD2 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NOD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOD2 were set to 18955195; 15459013; 11528384; 4056967
Phenotypes for gene: NOD2 were set to Blau syndrome 186580; Uveitis, granulomatous synovitis, camptodactyly, rash and cranial neuropathies, 30% develop Crohn colitis; Autoinflammatory Disorders; Caspase recruitment domain-containing protein 15 deficiency (CARD15)
COVID-19 research v0.36 NLRP3 Ellen McDonagh gene: NLRP3 was added
gene: NLRP3 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRP3 were set to 28847925; 11687797; 11992256; 29366613; 12522564; 12032915
Phenotypes for gene: NLRP3 were set to CINCA syndrome 607115; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation; Urticaria, SNHL, amyloidosis; Muckle-Wells syndrome 191900; Autoinflammatory Disorders; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772
COVID-19 research v0.36 NLRP12 Ellen McDonagh gene: NLRP12 was added
gene: NLRP12 was added to Viral susceptibility. Sources: Expert Review Green,Victorian Clinical Genetics Services,North West GLH,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRP12 were set to 29248470; 29178652; 27633793; 18230725; 27779193
Phenotypes for gene: NLRP12 were set to Autoinflammatory Disorders; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure.; preterm premature rupture of membranes (PPROM); Familial cold autoinflammatory syndrome 2, 611762
COVID-19 research v0.36 NLRC4 Ellen McDonagh gene: NLRC4 was added
gene: NLRC4 was added to Viral susceptibility. Sources: Expert Review Green,Victorian Clinical Genetics Services,North West GLH,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NLRC4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NLRC4 were set to 25217960; 25217959; 25385754; 27876626
Phenotypes for gene: NLRC4 were set to Autoinflammatory Disorders; Severe enterocolitis and macrophage activation syndrome; Autoinflammation with infantile enterocolitis 616050; ?Familial cold autoinflammatory syndrome 4 616115
Mode of pathogenicity for gene: NLRC4 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 NFKBIA Ellen McDonagh gene: NFKBIA was added
gene: NFKBIA was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NFKBIA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFKBIA were set to 18412279; 17931563; 14523047; 15337789
Phenotypes for gene: NFKBIA were set to Combined immunodeficiencies with associated or syndromic features; Anhidrotic ectodermal dysplasia, various infections (bacteria, mycobacteria, viruses and fungi), colitis, variable defects of skin, hair and teeth, T cell and monocyte dysfunction; Defects of TLR/NFkappa-B signalling; Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency 612132
Mode of pathogenicity for gene: NFKBIA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
COVID-19 research v0.36 NFKB2 Ellen McDonagh gene: NFKB2 was added
gene: NFKB2 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018
Mode of inheritance for gene: NFKB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFKB2 were set to 25237204; 24140114; 25524009; 24888602
Phenotypes for gene: NFKB2 were set to Recurrent sinopulmonary infections, alopecia and endorinopathies; Immunodeficiency, common variable, 10 615577; Unclassified antibody deficiency; Hypogammaglobuliaemia; central adrenal insufficiency; immune dysregulation; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies
COVID-19 research v0.36 NFKB1 Ellen McDonagh gene: NFKB1 was added
gene: NFKB1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: NFKB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFKB1 were set to 29477724; 26279205
Phenotypes for gene: NFKB1 were set to Unclassified antibody deficiency; Recurrent sinopulmonary infections, COPD, EBV proliferation, autoimmune cytopenias, alopecia and autoimmune thyroiditis; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Immunodeficiency, common variable, 12 616576
COVID-19 research v0.36 GATA2 Ellen McDonagh gene: GATA2 was added
gene: GATA2 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: GATA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GATA2 were set to 29588856; 21670465; 21765025; 2543925; 29724903
Phenotypes for gene: GATA2 were set to Susceptibility to mycobacteria, HPV, histoplasmosis, alveolar proteinosis, MDS/AML/CMMoL, lymphedema; Congenital neutropenia; Combined immunodeficiency with susceptibility to mycobacterial, viral and fungal infections; Immunodeficiency 21,614172; Congenital defects of phagocyte number or function; Monocytopenia and mycobacterial infection (MonoMAC); Monocytopenia with susceptibility to infections
COVID-19 research v0.36 ELANE Ellen McDonagh gene: ELANE was added
gene: ELANE was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: ELANE was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ELANE were set to Congenital neutropenia; Susceptibility to MDS/leukemia, Severe congenital neutropenia or cyclic neutropenia; Neutropenia, cyclic, 162800; Cyclic neutropenia; Congenital defects of phagocyte number or function; Neutropenia, severe congenital 1; Neutropenia, severe congenital 1, autosomal dominant, 202700
COVID-19 research v0.36 CXCR4 Ellen McDonagh Mode of inheritance for gene CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of pathogenicity for gene CXCR4 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Myelokathexis, isolated; Warts hypogammaglobulinemia infections and myelokathexis (WHIM); WHIM syndrome, 193670; WHIM syndrome; Warts (HPV) infection, neutropenia, low B cell number, hypogammaglobulinemia; Defects in Intrinsic and Innate Immunity for gene: CXCR4
Publications for gene CXCR4 were updated from to 12692554; 15536153
COVID-19 research v0.36 COPA Ellen McDonagh gene: COPA was added
gene: COPA was added to Viral susceptibility. Sources: Expert Review Green,Victorian Clinical Genetics Services,North West GLH,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: COPA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COPA were set to 28956095; 25894502; 29137621
Phenotypes for gene: COPA were set to Autoimmune interstitial lung disease-arthritis syndrome; Autoimmune inflammatory arthritis and interstitial lung disease with Th17 dysregulation and autoantibody production; Autoinflammatory Disorders; Autoimmune inflammatoy arthritis and interstial lung disease, 616414; COPA syndrome
COVID-19 research v0.36 CHD7 Ellen McDonagh gene: CHD7 was added
gene: CHD7 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHD7 were set to 15300250; 29159871; 25689927; 20052490; 18976358; 19403480; 26544072; 19187738; 29531775; 26563674; 21378379; 22461308; 18505430
Phenotypes for gene: CHD7 were set to CHARGE syndrome, 214800; Coloboma, heart anomaly, choanal atresia, intellectual disability, genital and ear anomalies, CNS malformation, some are SCID-like and have low TRECs; Immunodeficiency; Combined immunodeficiencies with associated or syndromic features; COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES; Charge syndrome
COVID-19 research v0.36 CASP10 Ellen McDonagh gene: CASP10 was added
gene: CASP10 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: CASP10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CASP10 were set to 16446975; 9028957; 10412980; 25663566; 16611303; 21447005
Phenotypes for gene: CASP10 were set to Adenopathies, splenomegaly, autoimmunity; Autoimmune lymphoproliferative syndrome, type II, 603909; Autoimmune lymphoproliferative syndrome (ALPS); Diseases of Immune Dysregulation
COVID-19 research v0.36 BACH2 Ellen McDonagh gene: BACH2 was added
gene: BACH2 was added to Viral susceptibility. Sources: Expert Review Green,North West GLH,NHS GMS,London North GLH,IUIS Classification February 2018
Mode of inheritance for gene: BACH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BACH2 were set to 27807919; 28530713; 27680876
Phenotypes for gene: BACH2 were set to Diseases of Immune Dysregulation; BACH2-related immunodeficiency and autoimmunity (BRIDA); hypogammaglobulinaemia; infantile onset enterocolitis; Lymphocytic colitis, sinopulmonary infections
COVID-19 research v0.36 TNFRSF13B Ellen McDonagh gene: TNFRSF13B was added
gene: TNFRSF13B was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,IUIS Classification December 2019,GRID V2.0,GOSH PID v.8.0,A- or hypo-gammaglobulinaemia v1.25,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: TNFRSF13B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNFRSF13B were set to 29114388; 28834165; 16007086; 16007087; 32086639; 18981294; 32048120
Phenotypes for gene: TNFRSF13B were set to IgA with IgG subclass deficiency; Immunodeficiency, common variable, 2; Immunodeficiency, common variable, 2, 240500; Variable clinical expression; Isolated IgG subclass deficiency; IGAD; Selective IgA deficiency; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Immunoglobulin A deficiency 2, 609529; CVID
COVID-19 research v0.36 STAT4 Ellen McDonagh gene: STAT4 was added
gene: STAT4 was added to Viral susceptibility. Sources: Expert Review Red,NHS GMS,London North GLH
Mode of inheritance for gene: STAT4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: STAT4 were set to {Systemic lupus erythematosus, susceptibility to, 11}, 612253
COVID-19 research v0.36 CFHR2 Ellen McDonagh gene: CFHR2 was added
gene: CFHR2 was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018
Mode of inheritance for gene: CFHR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CFHR2 were set to 32086639; 32048120
Phenotypes for gene: CFHR2 were set to Complement Deficiencies; Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility; Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections
COVID-19 research v0.36 TERT Ellen McDonagh gene: TERT was added
gene: TERT was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: TERT was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TERT were set to 16247010; 18460650; 15885610; 17785587
Phenotypes for gene: TERT were set to Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay
COVID-19 research v0.36 RAC2 Ellen McDonagh gene: RAC2 was added
gene: RAC2 was added to Viral susceptibility. Sources: Combined B and T cell defect v1.12,ESID Registry 20171117,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,SCID v1.6,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: RAC2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RAC2 were set to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859
Phenotypes for gene: RAC2 were set to Reticular dysgenesis; poststreptococcal glomerulonephritis; Congenital defects of phagocyte number or function; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Recurrent sinopulmonary infections, selective IgA defiency; urticaria; T-B- SCID; Poor wound healing, leukocytosis
COVID-19 research v0.36 NLRP1 Ellen McDonagh gene: NLRP1 was added
gene: NLRP1 was added to Viral susceptibility. Sources: North West GLH,NHS GMS,London North GLH,IUIS Classification February 2018,Expert Review Amber
Mode of inheritance for gene: NLRP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NLRP1 were set to 29850521; 27662089; 31484767; 27965258
Phenotypes for gene: NLRP1 were set to Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammation with arthritis and dyskeratosis; Autoinflammatory Disorders
COVID-19 research v0.36 MBL2 Ellen McDonagh Mode of inheritance for gene MBL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Mannose-binding lectin deficiency (MBL); Chronic infections, due to MBL deficiency; Mannose-Binding Protein Deficiency, 614372 for gene: MBL2
Publications for gene MBL2 were updated from 16170752; 19405982; 25818534; 16185324; 15838797 to 16185324; 28347655; 10888598; 19405982; 1458688; 16170752; 15838797; 7707811; 25818534
COVID-19 research v0.36 GUCY2C Ellen McDonagh gene: GUCY2C was added
gene: GUCY2C was added to Viral susceptibility. Sources: North West GLH,NHS GMS,GOSH PID v.8.0,London North GLH,Expert Review Amber
Mode of inheritance for gene: GUCY2C was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal