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| COVID-19 research v1.62 | ACE2 |
Arina Puzriakova changed review comment from: Preprint: Wooster et al 2020 - https://doi.org/10.1101/2020.06.18.20135152 Analysed association between ACE2 polymorphisms and COVID-19 severity in 62 patients. 10 SNPs were significantly associated with tissue expression of ACE2. Of these, 6 SNPs were also significantly associated with hospitalisation, after adjusting for sex and age (5 SNPs associated with higher tissue expression and increased need for hospitalisation due to COVID-19; and 1 SNP with lower tissue expression and reduced COVID-19 severity not requiring hospitalisation).; to: Preprint: Wooster et al 2020 - https://doi.org/10.1101/2020.06.18.20135152 Analysed association between ACE2 polymorphisms and COVID-19 severity in 62 patients. 10 SNPs were significantly associated with tissue expression of ACE2. Of these, 6 SNPs were also significantly associated with hospitalisation, after adjusting for sex and age (5 SNPs associated with higher tissue expression and increased need for hospitalisation due to COVID-19; and 1 SNP with lower tissue expression and reduced COVID-19 severity not requiring hospitalisation). |
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| COVID-19 research v1.62 | ACE2 | Arina Puzriakova commented on gene: ACE2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.23 | DPP4 |
Sarah Leigh changed review comment from: DPP4 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 2 grouping (experimental and/or genetic evidence, suggesting a biological role linking to corona viruses, may not be a GDA); to: DPP4 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 2 grouping (experimental and/or genetic evidence, suggesting a biological role linking to corona viruses, may not be a GDA). "Illumina review: Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. DPP4 acts as a receptor for MERS-CoV - PMID: 24554656 - Barlan et al. (2014). MERS virus cell entry begins with the receptor-binding domains (RBDs) of the MERS-CoV protein virus spike (S) protein binding to blades 4 and 5 of the 8-blade propeller domain of DPP4. PMID:23486063 - Raj et al. (2013) - identified DPP4 as a functional receptor for hCoV-EMS (MERS CoV). Evidence from mouse models of involvment in susceptibility to MERS-CoV infection. PMID:24599590 - Zhao et al. (2014) - noted that rodents are not susceptible to MERS-CoV. They used an adenovirus vector expressing human DPP4 to generate mice sensitized to infection with MERS-CoV. These mice developed pneumonia characterized by extensive inflammatory cell infiltration with virus clearance after 6 to 8 days in a type I IFN- and T cell-dependent manner. Treatment with poly(I:C) was also efficacious in this model. PMID: 25589660 - Agrawal et al. (2015) developed a transgenic mouse model expressing human DPP4 that was susceptible to MERS-CoV infection, with high titers of virus detectable in brain and lung and later in other organs. PMID: 26124093 - Pascal et al. (2015) - obtained a mouse model susceptible to intranasal infection with MERS-CoV. Human monoclonal antibodies binding to the MERS-CoV S protein neutralized all variants of the virus and prevented entry into target cells. The antibodies could both prevent and treat mice humanized for DPP4. Pascal et al. (2015) concluded that the model will be valuable for assessing treatments for MERS-CoV infection and disease. PMID:31883094 - Leist et al. (2020) - generated a mouse model susceptible to MERS-CoV infection - used C57BL/6J mice and CRISPR/Cas9 to substitute human residues at positions 288 and 330 (A288L and T330R). Strollo et al. (2020) and Bassedine et al. (2020) suggested that DPP4 could affect severity of infection and also be a therapeutic target: PMID:32336077 - Strollo et al. (2020) - propose a role for DDP4 as a functional receptor for SARS-CoV-2 and ask the question if DPP4 is directly involved in SARS-CoV-2 cell adhesion/virulence, and whether DPP4 inhibition might be a therapeutic strategy for preventing infection. PMID:32394639 - Bassedine et al. (2020) - modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. Notes that increased DPP4 expression and activity are associated with diabetes, obesity, and metabolic syndrome, all of which have been reported to influence COVID‐19 severity. DPP4 inhibitors (gliptins), which vary in their interactions with the active site of the enzyme, may have immunomodulatory and cardioprotective effects that could be beneficial in COVID‐19 cases. PMID:31964246 - Keline-Weber at al. (2020) - Identified 14 polymorphisms in DPP4 from public databases that alter amino acid residus required for MERS-CoV S binding. Introduction of the respective variants into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients. |
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| COVID-19 research v1.17 | CLEC4M |
Sarah Leigh changed review comment from: CLEC4M was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 2 grouping (experimental and/or genetic evidence, suggesting a biological role linking to corona viruses, may not be a GDA); to: CLEC4M was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 2 grouping (experimental and/or genetic evidence, suggesting a biological role linking to corona viruses, may not be a GDA). Illumina review: CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It functions as a cellular receptor for variety of viruses, including HIV-1, hepatitis C, Ebola, and SARS-coronavirus. A highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases, however, genetic association studies have shown conflicting results about these associations (PMID:16991095;16369534;12738250;16364081;17321900;18697825;17534354;17534355). From OMIM: Associated with protection against SARs infection. PMID: 15496474: Jeffers et al. (2004) identified the cellular gylcoprotein CD209L (CLEC4M) as as an alternative receptor for SARS-CoV. CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses, including Ebola and Sindbis, also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Jeffers et al. (2004) suggested that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis. PMID 16369534: Chan et al. (2006) - demonstrated that individuals homozygous for CLEC4M tandem repeats are less susceptible to SARS infection. CLEC4M was expressed in both non-SARS and SARS-CoV-infected lung. Compared with cells heterozygous for CLEC4M, cells homozygous for CLEC4M showed higher binding capacity for SARS-CoV, higher proteasome-dependent viral degradation, and a lower capacity for trans infection. Thus, homozygosity for CLEC4M plays a protective role during SARS infection. PMID: 17534354: Tang et al. (2007) - performed genotyping studies in SARS patients and controls and found no support for an association between homozygosity for CLEC4M and protection against SARS. PMID:17534355: Zhi et al. (2007) also failed to replicate the study by Chan et al. (2006). Chan et al. (2007) disputed the validity of both studies. PMID 18697825:Li et al. (2008) - genotyped SNPs in CLEC4M and other genes in the C-type lectin cluster in 181 Chinese SARS patients and 172 controls from an ethnically matched population and found no significant association with disease predisposition or prognosis. However, they detected a population stratification of the CLEC4M variable number tandem repeat (VNTR) alleles in a sample of 1,145 Han Chinese from different parts of China (northeast, south, and southwest). Analysis extended to 742 individuals from 7 ethnic minorities showed that those located along the Silk Road in northwestern China, where there is significant admixture with the European gene pool, had a low level of homozygosity, similar to European populations. Li et al. (2008) concluded that there is no SARS predisposition allele in the lectin gene cluster at chromosome 19p13.3, and that the previously reported association with polymorphisms in the CLEC4M neck region may be due to population stratification. |
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| COVID-19 research v1.10 | ACE2 | Sarah Leigh commented on gene: ACE2: ACE2 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 2 grouping (experimental and/or genetic evidence, suggesting a biological role linking to corona viruses, may not be a GDA) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.9 | ACE2 | Alison Coffey reviewed gene: ACE2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32228252; Phenotypes: ; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.347 | DEFA1 | Alison Coffey commented on gene: DEFA1: Evidence Summary from Illumina curation team: DEFA1, or HNP1, is a member of the defensin family of host defense peptides, a group of microbicidal and cytotoxic peptides made by neutrophils. Defensins are known to have a role in innate immunity as a core host-protective component against bacterial, viral and fungal infections (Xu and Wuyaun, 2020). Defensins have direct antiviral activity in cell culture, with varied mechanisms for individual viruses. Defensins also have a potent immunomodulatory activity that can alter innate and adaptive immune responses to viral infection and are able to target multiple steps of host-virus interactions to reduce infectivity of both enveloped and non-enveloped viruses. Targets include viral envelopes, glycoproteins, and capsids or host cells. DEFA1 is well-recognized for its direct anti-HIV activity, it also restrains HIV-1 uptake by inhibiting Env-mediated viral fusion and downregulating host cell surface expression of CD4 and coreceptor CXCR4. Post-entry inhibition of enveloped viruses such as HIV-1 and influenza by DEFA1 is mediated through interfering with cell signaling pathways such as PKC that are required for viral replication (Xu and Wuyaun, 2020). An unpublished study by Kit and Kit (2020), demonstrated in silico that the affinity of human alpha-defensins 1, 2, 3 and 5 to SARS-CoV-2 spike protein is higher than that of the SARS-CoV-2 spike protein towards ACE2. The authors suggest that these alpha-defensins may serve as primary factors in protecting lung tissue from COVID-19 viral infection. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.332 | ACE2 | Catherine Snow reviewed gene: ACE2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.304 | SLC6A19 |
Eleanor Williams gene: SLC6A19 was added gene: SLC6A19 was added to COVID-19 research. Sources: Literature Mode of inheritance for gene: SLC6A19 was set to Unknown Added comment: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Sources: Literature |
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| COVID-19 research v0.303 | ACE2 |
Eleanor Williams changed review comment from: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2.; to: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2. |
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| COVID-19 research v0.303 | ACE2 |
Eleanor Williams edited their review of gene: ACE2: Added comment: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2.; Changed publications: 32015507, https://doi.org/10.1101/2020.05.15.098616 |
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| COVID-19 research v0.303 | TMPRSS4 |
Eleanor Williams gene: TMPRSS4 was added gene: TMPRSS4 was added to COVID-19 research. Sources: Literature Mode of inheritance for gene: TMPRSS4 was set to Unknown Publications for gene: TMPRSS4 were set to https://doi.org/10.1101/2020.05.12.091314 Added comment: Preprint: Wruck and Adjaye https://doi.org/10.1101/2020.05.12.091314 - describe a meta-analysis focussing on the transcriptome data from human lung epithelial cells including samples infected with SARS-CoV-2 from a study described by Blanco Melo et al.12. The exploration was directed to co-expression with the known CoV-2 receptor ACE2. 72 genes significantly co-expressed with ACE2. Of the transmembrane serine proteases, the most significantly coexpressed with ACE2 was TMPRSS4, suggesting it to be a putative druggable target. Pathway analysis revealed papilloma virus infection amongst the most significantly correlated pathways. Sources: Literature |
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| COVID-19 research v0.299 | ACE2 |
Eleanor Williams changed review comment from: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2- RBD complexes of different species allowing us to anticipate the effects of amino acid sequence variation of ACE2 on viral entry; to: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2-RBD complexes of different species allowing us to anticipate the effects of amino acid sequence variation of ACE2 on viral entry |
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| COVID-19 research v0.299 | ACE2 |
Eleanor Williams commented on gene: ACE2: Preprint: Pach et al https://doi.org/10.1101/2020.05.14.092767 - by looking at species that are susceptible and non-susceptible to SARS-COV-2, they have developed dynamic computational models for ACE2- RBD complexes of different species allowing us to anticipate the effects of amino acid sequence variation of ACE2 on viral entry |
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| COVID-19 research v0.298 | ACE2 | Eleanor Williams commented on gene: ACE2: Preprint: https://doi.org/10.1101/2020.05.12.20098160 - Shovlin and Vizcaychip - variants in 213,158 exomes/genomes were integrated for ACE2 . ACMG/AMP-based pathogenicity criteria were applied. Modelling the ″COVID-resistant ″ state where pathogenic alleles would be beneficial, nine null alleles met PVS1. Thirty-seven variants met PM1 based on critical location +/-PP3 based on computational modelling. Modelling a ″COVID-susceptible ″ state, 31 variants in four upstream open reading frames and 5′ untranslated regions could meet PM1, and may have differential effects if aminoglycoside antibiotics were prescribed for pneumonia and sepsis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.232 | ACE2 | Eleanor Williams changed review comment from: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations.; to: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations. East Asian populations have much higher AFs in the eQTL variants associated with higher ACE2 expression in tissues. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.232 | ACE2 | Eleanor Williams Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651; 32015507 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.231 | ACE2 | Eleanor Williams commented on gene: ACE2: PMID: 32133153 Cao et al 2020 - Analyzed coding-region variants in ACE2 and the eQTL variants, which may affect the expression of ACE2 using the GTEx database to compare the genomic characteristics of ACE2 among different populations. Their findings indicated that no direct evidence was identified genetically supporting the existence of coronavirus S-protein binding-resistant ACE2 mutants in different populations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.230 | ACE2 | Eleanor Williams commented on gene: ACE2: PMID: 32249956 Hussain et al 2020 - show through molecular modelling that ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein of SARS-CoV-2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.227 | TMPRSS2 | Eleanor Williams Added comment: Comment on publications: Adding pubmed:32327758 - using single cell RNA-sequencing they confirmed the expression of ACE2 in multiple tissues shown in previous studies with added information on tissues not previously investigated, including nasal epithelium and cornea and its co-expression with TMPRSS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.206 | 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 v0.205 | ACE2 | Sarah Leigh commented on gene: ACE2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.204 | ACE2 | Rebecca Foulger commented on gene: ACE2: Added 'treatable' tag based on preprint http://biorxiv.org/cgi/content/short/2020.05.07.082230 which suggests that a modified ACE2 peptide could act as a treatment to block the viral receptor forming a complex with ACE2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.204 | ACE2 | Rebecca Foulger Tag treatable tag was added to gene: ACE2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.200 | IFNL3 |
Catherine Snow gene: IFNL3 was added gene: IFNL3 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: IFNL3 was set to Unknown Review for gene: IFNL3 was set to AMBER Added comment: IFNL3 was identified in preprint https://doi.org/10.1101/2020.04.26.20080408 "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. Sources: Literature |
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| COVID-19 research v0.199 | IFNL4 |
Catherine Snow changed review comment from: IFNL4 was identified in preprint "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation. Sources: Literature; to: IFNL4 was identified in preprint https://doi.org/10.1101/2020.04.26.20080408 "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation. Sources: Literature |
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| COVID-19 research v0.199 | IFNL4 |
Catherine Snow gene: IFNL4 was added gene: IFNL4 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: IFNL4 was set to Unknown Publications for gene: IFNL4 were set to 31776283 Review for gene: IFNL4 was set to AMBER Added comment: IFNL4 was identified in preprint "A gene locus that controls expression of ACE2 in virus infection" A GWAS for performed for ACE2 expression in HCV-infected liver tissue from 195 individuals. it was discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. PMID: 31776283 Investigates the IFNL4 gene - it acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation. Sources: Literature |
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| COVID-19 research v0.165 | ACE2 | Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.22.056127v1 show that ACE2 levels in the respiratory tract did not increase in association with risk factors for severe COVID-19 (e.g. age and underlying chronic comorbidities). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | ACE2 | Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.050534v1 conclude that higher expression of ACE2 facilitated by natural variations (with different frequencies in different populations) results in ACE2 homo-dimerization which is disadvantageous for TMPRSS2 mediated cleavage of ACE2. They propose that monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | TMPRSS2 | Rebecca Foulger commented on gene: TMPRSS2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.056259v2 suggests that ACE2 and TMPRSS2 co-expression in the prostate may explain sex differences in the observed COVID-19 disaparities. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | ACE2 | Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.056259v2 suggests that ACE2 and TMPRSS2 co-expression in the prostate may explain sex differences in the observed COVID-19 disaparities. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.163 | TMPRSS2 | Rebecca Foulger commented on gene: TMPRSS2: Preprint https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 Lopera et al shows a LACK of association between genetic variants at ACE2 and TMPRSS2 and human quantitative phenotypes. The authors recognise that the SARS-CoV-2 virus uses ACE2 for cell invasion, and the serine protease TMPRSS2 for S protein priming and therefore they investigated whether genetic variation in these two genes modulates an individual's genetic predisposition to infection and virus clearance. They examined 178 quantitative phenotypes in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2: none reached the threshold for significance though these variants may play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.163 | ACE2 | Rebecca Foulger commented on gene: ACE2: Preprint https://www.medrxiv.org/content/10.1101/2020.04.22.20074963v1 Lopera et al shows a LACK of association between genetic variants at ACE2 and TMPRSS2 and human quantitative phenotypes. The authors recognise that the SARS-CoV-2 virus uses ACE2 for cell invasion, and the serine protease TMPRSS2 for S protein priming and therefore they investigated whether genetic variation in these two genes modulates an individual's genetic predisposition to infection and virus clearance. They examined 178 quantitative phenotypes in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2: none reached the threshold for significance though these variants may play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.163 | ACE2 | Sophie Hambleton reviewed gene: ACE2: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.161 | ACE2 |
Eleanor Williams changed review comment from: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.; to: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV. PMID: 32142651 - Hoffman et al 2020 - demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry |
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| COVID-19 research v0.161 | ACE2 | Eleanor Williams Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.160 | ACE2 | Eleanor Williams edited their review of gene: ACE2: Added comment: PMID: 32015507 - Zhou et al 2020 - Nature article. Confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.; Changed publications: 32015507 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.149 | ACE2 | Rebecca Foulger Classified gene: ACE2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.149 | ACE2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Multiple functional data demonstrates a role for ACE2 as a receptor for Coronaviruses. Plus a vast amount of preprint data that suggests SNPs in ACE2 should be explored for regional differences. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.149 | ACE2 | Rebecca Foulger Gene: ace2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.148 | TMPRSS2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green on this research panel: Known mechanisms for involvement in viral infection (including proteolytic cleavage of the viral receptor, ACE2) plus variants identified in preprints as candidates for COVID-19 severity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.145 | ACE2 | Rebecca Foulger commented on gene: ACE2: ACE2 gene present in the UniProt COVID portal (https://covid-19.uniprot.org/ 6-April-2020) which provides the latest available pre-release UniProtKB data for the SARS-CoV-2 coronavirus and other entries relating to the COVID-19 outbreak. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.140 | ACE2 |
Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asseleta et al ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients. ; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asselta et al ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients. |
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| COVID-19 research v0.140 | ACE2 |
Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. ; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.12.037580v1 - Asseleta et al ACE2 SNP rs2285666 (also called G8790A), more common in Italians and Europeans that East Asians. This variant was extensively studied as a potential risk factor for hypertension, type 2 diabetes, and coronary artery disease hence possibly constituting a predisposing factor also for the comorbidities observed in COVID-19 patients. |
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| COVID-19 research v0.140 | DMBT1 |
Eleanor Williams gene: DMBT1 was added gene: DMBT1 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: DMBT1 was set to Unknown Review for gene: DMBT1 was set to RED Added comment: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.16.045617v1 - Han et al Found using single cell transcriptomics that DMBT1 (a viral binding scavenger) was highly expressed in alveolar type II cells relative to other lung epithelial subsets and its expression positively correlated with ACE2. Sources: Literature |
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| COVID-19 research v0.138 | ACE2 |
Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. Preprint - https://www.medrxiv.org/content/10.1101/2020.04.03.20047977v1 - Renieri et al Using the Network of Italian Genomes (NIG), they mined around 7000 exomes from 5 different Centers looking for ACE2 variants. Identified variants with a potential impact on protein stability. 3 missense changed identified that have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants that are likely to interfere with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. |
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| COVID-19 research v0.138 | TRIB3 |
Eleanor Williams gene: TRIB3 was added gene: TRIB3 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: TRIB3 was set to Unknown Publications for gene: TRIB3 were set to 27252525; https://www.biorxiv.org/content/10.1101/2020.04.07.030767v1 Added comment: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.030767v1 - de Moraes et al Analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. Identified TRIB3 expression was decreased in older males. Found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. PMID: 27252525 - Tran et al 2016- Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased Hepatitis C viral replication Sources: Literature |
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| COVID-19 research v0.137 | ACE2 |
Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.07.024752v1 - Stawiski et al Aassessed ACE2 protein-altering variations from a number of databases including the gnomAD, RotterdamStudy, ALSPAC, GenomeAsia100k, HGDP, TOMMO-3.5kjpnv2, IndiGen, and HGDP. Identified variants that are likely to either increase or decrease the binding affinity of ACE2 to the S-protein and thereby alter the ability of the virus to infect the host cell. Preprint - https://www.biorxiv.org/content/10.1101/2020.03.16.994236v1 Procko Made a library of coding sequence of ACE2 containing all possible single amino acid substitutions at 117 sites spanning the interface with S and lining the substrate cavity. The ACE2 library was transiently expressed in human Expi293F cells and cells were then incubated in medium containing the receptor binding domain of SARS-CoV-2 fused C-terminallyto superfolder GFP. Sorted cells with high and low binding and the transcripts sequenced to identify the variants. |
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| COVID-19 research v0.137 | ACE2 |
Eleanor Williams changed review comment from: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations.; to: Preprint - https://www.biorxiv.org/content/10.1101/2020.04.14.041434v1 - Li et al Total death rate is higher in Spain compared to China, so looked differences between the Asian and Caucasian populations for ACE2 polymorphisms using gnomAD v2.1 exomes and compare the variability of hACE2 expression in peripheral blood among eight different populations. Four genetic variants reached statistical significance for differences in MAF between the two populations N720D, K26R, N638S, I468V. Found small differences in expression of hACE2 among various populations. Preprint - https://www.biorxiv.org/content/10.1101/2020.04.05.026633v1 - Gibson et al Analyse ACE2 variants in the gnomAD database and identify 15 missense variants likely to affect the affinity of the human ACE2 protein for the viral spike protein and estimated the change in binding energy of the 15 missense variants. |
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| COVID-19 research v0.137 | ACE2 | Eleanor Williams commented on gene: ACE2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.111 | TMPRSS2 |
Catherine Snow changed review comment from: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2. This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878 Sources: Literature; to: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2. Papers identified include: PMID: 25904605 which reported that higher TMPRSS2 expression variant, rs2070788 GG genotype, was associated with higher susceptibility to severe illness in patients with A(H1N1)pdm09 influenza. PMID: 24600012 showed that TMPRSS2 is the key host protease that activates IAVs in vivo through proteolytic cleavage of their HA proteins PMID: 24522916 looked at knockout mice that do not express TMPRSS2 that are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878 Sources: Literature |
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| COVID-19 research v0.110 | TMPRSS2 |
Catherine Snow gene: TMPRSS2 was added gene: TMPRSS2 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: TMPRSS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMPRSS2 were set to 31488196 Review for gene: TMPRSS2 was set to AMBER Added comment: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2. This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878 Sources: Literature |
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| COVID-19 research v0.101 | ACE2 | Rebecca Foulger commented on gene: ACE2: Added ACE2 to the panel as an Amber gene: many papers demonstrate that ACE2 acts as a cell receptor for Coronaviruses (e.g. PMIDs 32142651, 15897467, 14647384). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.101 | ACE2 | Rebecca Foulger Classified gene: ACE2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.101 | ACE2 | Rebecca Foulger Gene: ace2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.100 | ACE2 |
Rebecca Foulger gene: ACE2 was added gene: ACE2 was added to Viral susceptibility. Sources: Other Mode of inheritance for gene: ACE2 was set to Unknown Publications for gene: ACE2 were set to 14647384; 15897467; 16007097; 32142651 Review for gene: ACE2 was set to AMBER Added comment: Sources: Other |
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