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| COVID-19 research v1.142 | RNU4ATAC | Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from 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 to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.136 | DCLRE1B | Achchuthan Shanmugasundram Phenotypes for gene: DCLRE1B were changed from 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 to Dyskeratosis congenita, autosomal recessive 8, OMIM:620133 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.134 | TERT | Arina Puzriakova Phenotypes for gene: TERT were changed from Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.98 | NLRP12 | Arina Puzriakova Phenotypes for gene: NLRP12 were changed from 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 to Familial cold autoinflammatory syndrome 2, OMIM:611762; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Preterm premature rupture of membranes (PPROM); Autoinflammatory Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.79 | ATM | Arina Puzriakova Phenotypes for gene: ATM were changed from Ataxia telangiectasia (ATM); immunodeficiency; Combined immunodeficiencies with associated or syndromic features; Ataxia, telangiectasia, pulmonary infections, lymphoreticular and other malignancies, increased alpha fetoprotein, increased radiosensitivity, chromosomal instability and chromosomal translocations; Ataxia-telangiectasia, 208900 to Ataxia-telangiectasia, OMIM:208900; Combined immunodeficiencies with associated or syndromic features; Ataxia, telangiectasia, pulmonary infections, lymphoreticular and other malignancies, increased alpha fetoprotein, increased radiosensitivity, chromosomal instability and chromosomal translocations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.26 | HLA-C |
Sarah Leigh changed review comment from: HLA-C was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility); to: HLA-C was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility). Illumina review: From OMIM: PMID: 11386265 - Gao et al. (2001) concluded that the previously observed association of HLA-Cw*04 with progression to AIDS was due to its linkage disequilibrium with HLA-B*35-Px alleles. PMID:17641165 - Fellay et al. (2007) identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these lies within an endogenous retroviral element and is associated with major histocompatibility allele HLA-B*5701 (142830.0003), whereas a second is located near the HLA-C gene. PMID:19933563 - Thomas et al. (2009) - Genotyped a previously identified varinat 35 kb upstream of the HLA-C gene in 1,698 patients of European ancestry with HIV. Tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. Found that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high surface expression better control viremia and progress more slowly to AIDS. Thomas et al. (2009) concluded that high HLA-C expression results in more effective control of HIV-1, possibly through better antigen presentation to cytotoxic T lymphocytes. PMID 21051598: International HIV Controllers Study performed a GWAS in a multiethnic cohort of HIV-1 controllers and progressors, and analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins and demonstrated HLA-C expression affects response to HIV - higher HLA-C expression is associated with better control of HIV-1. |
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| COVID-19 research v1.24 | FUT2 |
Sarah Leigh changed review comment from: FUT2 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility); to: FUT2 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility). Illumina review: PMID: 30845670: Nordgren et al. (2019) (Review) The FUT2 gene encodes FUT2 enzyme, which catalyzes the transfer of fucose to the terminal galactose on glycan chains of cell surface glycoproteins and glycolipids, allowing the synthesis of histo-blood group antigens (HBGAs). The FUT2 gene is expressed predominately in epithelial (mucosal) tissues. Individuals with inactivated FUT2 enzyme, known as “non secretors” do not express blood group antigens in these tissues and are resistant to several norovirus genotypes. FUT2 polymorphisms with known effect on secretor status are present in different populations and are reviewed by Nordgren et al. (2019). |
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| COVID-19 research v1.15 | CD209 |
Sarah Leigh changed review comment from: CD209 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility); to: CD209 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility). Illumina review: One SNP associated with susceptibility to HIV infection, severity of dengue disease, increased risk of TB and severity of SARS infection. Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. The receptor returns to the cell membrane surface and the pathogen-derived antigens are presented to resting T-cells via MHC class II proteins to initiate the adaptive immune response. From OMIM:The C-type lectin receptors are involved in the primary interface between host and pathogens. PMID:15564514: Martin et al. (2004) - European Americans at risk for parenteral HIV infection were more likely to carry the -336C SNP in the promoter of DCSIGN. This association was not observed in those at risk for mucosally acquired infection. Although the -336C SNP was common in African Americans, no significant association with risk of infection was observed in this group. PMID:15838506: Sakuntabhai et al. (2005) found that the same CD209 promoter polymorphism reported by Martin et al. (2004) (-336A>G in this study), was associated with severity of dengue disease. Specifically, the G allele of the variant was associated with strong protection against dengue fever as opposed to dengue hemorrhagic fever. PMID:16379498:Barreiro et al. (2006) looked at CD209 polymorphisms in 351 TB patients and 360 healthy controls from a South African Coloured population living in communities with some of the highest reported incidence rates of TB in the world. Identified two variants in the CD209 promoter, -871A and -336G, that were associated with increased risk of TB. PMID:20864747: Chan et al. (2010) - A single nucleotide polymorphism in the promoter region of the DC-SIGN gene is associated with disease severity in SARS. In the DC_SIGN promoter region, a single SNP, -336A>G has been found to affect transcription of DC-SIGN in vitro and is associated with susceptibility for HIV-1 and M. tuberculosis infectsions and with the severity of dengue (PMID:15838506;15838506;16379498). Large case-control study - genotyped the SNP in 824 SARS patients and 471 controls. Showed no association with susceptibility to infection but SARS patients carrying the DC-SIGN promoter -336G variant had lower risk of having higher lactate dehydrogenase levels on admission, an independent prognostic indicator for severity of SARS-CoV infection. In vitro functional studies demonstrated that the DC-SIGN -336G promoter provided a less effective binding site and lower promoter activity, which may lead to reduced DC-SIGN protein expression and hence may contribute to a reduced immune-response with reduced lung injury during the progression of SARS infection. |
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| 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). |
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| 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 |
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| 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. |
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| 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. |
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| 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). |
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| 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. |
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| 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). |
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| 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 | 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 | 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 v0.319 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 v0.268 | 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 |
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| 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 |
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| 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 |
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| 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. |
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| 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 v0.171 | 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 v0.151 | 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 |
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| 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 |
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| 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. |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| COVID-19 research v0.36 | RTEL1 |
Ellen McDonagh gene: RTEL1 was added gene: RTEL1 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: RTEL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: RTEL1 were set to 23959892; 23453664; 23591994 Phenotypes for gene: RTEL1 were set to Combined immunodeficiencies with associated or syndromic features; Hoyeraal-Hreidarsson syndrome/ Dyskeratosis congenita, 4 615190; 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; Dyskeratosis congenita, 5 615190 |
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| COVID-19 research v0.36 | PARN |
Ellen McDonagh gene: PARN was added gene: PARN 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: PARN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PARN were set to 25848748; 26342108; 25893599 Phenotypes for gene: PARN were set to Pulmonary fibrosis and/or bone marrow failure,telomere-related, 4 616371; Dyskeratosis congenita, autosomal recessive 6 616353; 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 |
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| COVID-19 research v0.36 | ZNF341 |
Ellen McDonagh gene: ZNF341 was added gene: ZNF341 was added to Viral susceptibility. Sources: Expert Review Red,Literature,IUIS Classification December 2019 Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF341 were set to 32086639; 29907691; 32048120; 29907690 Phenotypes for gene: ZNF341 were set to Hyper-IgE syndrome; Combined immunodeficiencies with associated or syndromic features; Bacterial infections, mild facial dysmorphism, pneumatoceles, hyperextensible joints, bone fractures, retention of primary teeth |
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| COVID-19 research v0.36 | WRAP53 |
Ellen McDonagh gene: WRAP53 was added gene: WRAP53 was added to Viral susceptibility. Sources: IUIS Classification February 2018,IUIS Classification December 2019 Mode of inheritance for gene: WRAP53 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WRAP53 were set to 32086639; 32048120 Phenotypes for gene: WRAP53 were set to 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 |
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| COVID-19 research v0.36 | TNFSF11 |
Ellen McDonagh gene: TNFSF11 was added gene: TNFSF11 was added to Viral susceptibility. Sources: IUIS Classification February 2018,IUIS Classification December 2019 Mode of inheritance for gene: TNFSF11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNFSF11 were set to 32086639; 32048120 Phenotypes for gene: TNFSF11 were set to Osteopetrosis with severe growth retardation; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity |
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| COVID-19 research v0.36 | STN1 |
Ellen McDonagh gene: STN1 was added gene: STN1 was added to Viral susceptibility. Sources: IUIS Classification February 2018,IUIS Classification December 2019 Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STN1 were set to 32086639; 32048120 Phenotypes for gene: STN1 were set to 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 |
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| COVID-19 research v0.36 | RNU4ATAC |
Ellen McDonagh gene: RNU4ATAC was added gene: RNU4ATAC was added to Viral susceptibility. Sources: IUIS Classification February 2018,IUIS Classification December 2019 Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU4ATAC were set to 32086639; 32048120 Phenotypes for gene: RNU4ATAC were set to 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 |
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| COVID-19 research v0.36 | LIG1 |
Ellen McDonagh gene: LIG1 was added gene: LIG1 was added to Viral susceptibility. Sources: Emory Genetics Laboratory,Expert Review,Other,IUIS Classification December 2019,Expert Review Red,Literature,IUIS Classification February 2018 Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LIG1 were set to 30395541; 1581963; 32086639; 32048120 Phenotypes for gene: LIG1 were set to 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 |
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| COVID-19 research v0.36 | IL6ST |
Ellen McDonagh gene: IL6ST was added gene: IL6ST was added to Viral susceptibility. Sources: Expert Review Red,Literature,IUIS Classification December 2019 Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6ST were set to 31235509; 32086639; 30309848; 28747427; 32048120 Phenotypes for gene: IL6ST were set to 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 |
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| COVID-19 research v0.36 | NOP10 |
Ellen McDonagh gene: NOP10 was added gene: NOP10 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: NOP10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NOP10 were set to 17507419 Phenotypes for gene: NOP10 were set to 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 |
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| COVID-19 research v0.36 | CTC1 |
Ellen McDonagh gene: CTC1 was added gene: CTC1 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: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTC1 were set to 22267198; 32086639; 32048120 Phenotypes for gene: CTC1 were set to 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 |
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| COVID-19 research v0.36 | VPS13B |
Ellen McDonagh gene: VPS13B was added gene: VPS13B 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: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS13B were set to 24311531; 15211651; 12730828; 20461111; 15154116 Phenotypes for gene: VPS13B were set to Cohen syndrome, 216550; Congenital defects of phagocyte number or function; Dysmorphism, mental retardation, obesity, deafness, neutropenia; Cohen syndrome |
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| COVID-19 research v0.36 | USB1 |
Ellen McDonagh gene: USB1 was added gene: USB1 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: USB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USB1 were set to 20503306; 20004881 Phenotypes for gene: USB1 were set to Poikiloderma with neutropenia, 604173; Clericuzio-type poikiloderma with neutropenia syndrome; Congenital defects of phagocyte number or function; Retinopathy, developmental delay, facial dysmorphisms, poikiloderma |
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| COVID-19 research v0.36 | TTC37 |
Ellen McDonagh gene: TTC37 was added gene: TTC37 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: TTC37 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC37 were set to 29383842; 25688341; 28292286; 21120949; 28944135; 20176027 Phenotypes for gene: TTC37 were set to Recurrent bacterial and viral infections, Abnormal hair findings: trichorrhexis nodosa; Trichohepatoenteric syndrome 1, 222470; Intrauterine growth retardation, woolly hair; intractable diarrhoea in infancy requiring total parenteral nutrition; Hypogammaglobulinaemia; Predominantly Antibody Deficiencies; facial dysmorphism; immune dysfunction; Trichohepatoenteric syndrome |
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| COVID-19 research v0.36 | SMARCAL1 |
Ellen McDonagh gene: SMARCAL1 was added gene: SMARCAL1 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: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMARCAL1 were set to 17089404; 11799392 Phenotypes for gene: SMARCAL1 were set to Schimke disease; Combined immunodeficiencies with associated or syndromic features; Schimke immunoosseous dysplasia 242900; Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure |
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| COVID-19 research v0.36 | SLC35C1 |
Ellen McDonagh gene: SLC35C1 was added gene: SLC35C1 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: SLC35C1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC35C1 were set to 11326279; 24403049; 11213799; 12116250; 11326280; 1279426 Phenotypes for gene: SLC35C1 were set to Mild LAD type 1 features with hh-blood group, growth retardation, developmental delay; Congenital defects of phagocyte number or function; Leukocyte adhesion deficiency (LAD); Congenital disorder of glycosylation, type IIc 266265 |
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| COVID-19 research v0.36 | NHP2 |
Ellen McDonagh gene: NHP2 was added gene: NHP2 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: NHP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NHP2 were set to 25182133; 18523010; 20301779; 20008900; 25907943 Phenotypes for gene: NHP2 were set to Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome; Dyskeratosis congenita, autosomal recessive 2 613987; 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 |
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| COVID-19 research v0.36 | NHEJ1 |
Ellen McDonagh gene: NHEJ1 was added gene: NHEJ1 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,SCID v1.6,IUIS Classification February 2018 Mode of inheritance for gene: NHEJ1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NHEJ1 were set to Combined immunodeficiency; Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291; Nl NK, radiation sensitive, microcephaly; Immunodeficiencies affecting cellular and humoral immunity; Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation; T-B+ SCID; Cernunnos/XLF deficiency; T-B- SCID |
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| COVID-19 research v0.36 | GINS1 |
Ellen McDonagh gene: GINS1 was added gene: GINS1 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,NHS GMS,London North GLH,IUIS Classification February 2018 Mode of inheritance for gene: GINS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS1 were set to 28414293 Phenotypes for gene: GINS1 were set to Immunodeficiency 55, 617827; NK cell deficiency; chronic neutropenia; Neutropenia, IUGR, NK cells very low; GINS1 deficiency; Combined immunodeficiencies with associated or syndromic features; intrauterine growth retardation |
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| COVID-19 research v0.36 | DCLRE1B |
Ellen McDonagh gene: DCLRE1B was added gene: DCLRE1B 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: DCLRE1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DCLRE1B were set to 20479256 Phenotypes for gene: DCLRE1B were set to 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 |
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| COVID-19 research v0.36 | ATM |
Ellen McDonagh gene: ATM was added gene: ATM 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: ATM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATM were set to 27421701; 2136770; 27884168; 7792600; 2005780 Phenotypes for gene: ATM were set to Ataxia telangiectasia (ATM); immunodeficiency; Combined immunodeficiencies with associated or syndromic features; Ataxia, telangiectasia, pulmonary infections, lymphoreticular and other malignancies, increased alpha fetoprotein, increased radiosensitivity, chromosomal instability and chromosomal translocations; Ataxia-telangiectasia, 208900 |
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| COVID-19 research v0.36 | AK2 |
Ellen McDonagh gene: AK2 was added gene: AK2 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,SCID v1.6,IUIS Classification February 2018 Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AK2 were set to 19043417; 19043416 Phenotypes for gene: AK2 were set to Reticular dysgenesis, AK2 deficiency; Granulocytopenia and deafness; Reticular dysgenesis, 267500; Reticular dysgenesis with sensorineural deafness; Reticular Dysgenesis AK2 (SCID); Immunodeficiencies affecting cellular and humoral immunity |
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