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| COVID-19 research v1.62 | TMPRSS2 | Arina Puzriakova Tag treatable tag was added to gene: TMPRSS2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v1.62 | TMPRSS2 | Arina Puzriakova commented on gene: TMPRSS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.331 | TMPRSS2 | Catherine Snow Mode of inheritance for gene: TMPRSS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.304 | TMPRSS2 | Eleanor Williams reviewed gene: TMPRSS2: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.15.098616; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.304 | SLC6A19 |
Eleanor Williams gene: SLC6A19 was added gene: SLC6A19 was added to COVID-19 research. Sources: Literature Mode of inheritance for gene: SLC6A19 was set to Unknown Added comment: Preprint: Gupta et al https://doi.org/10.1101/2020.05.15.098616 Using the Viral Integrated Structural Evolution Dynamic Database and population genomic databases they identified 47 potential functional missense variants within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Sources: Literature |
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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 v0.230 | TMPRSS2 | Eleanor Williams Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843; 25904605; 24600012; 24522916; 32327758 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.229 | TMPRSS2 | Eleanor Williams Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.229 | TMPRSS2 | Eleanor Williams Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.227 | TMPRSS2 | Eleanor Williams Added comment: Comment on publications: Adding pubmed:32327758 - using single cell RNA-sequencing they confirmed the expression of ACE2 in multiple tissues shown in previous studies with added information on tissues not previously investigated, including nasal epithelium and cornea and its co-expression with TMPRSS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.227 | TMPRSS2 | Eleanor Williams Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843; 25904605; 24600012; 24522916 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.217 | MX1 |
Sarah Leigh gene: MX1 was added gene: MX1 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: MX1 was set to Unknown Publications for gene: MX1 were set to 3162334; 14872030; 21935451; https://doi.org/10.1101/2020.05.04.075911 Review for gene: MX1 was set to AMBER Added comment: MX1 is an interferon-induced protein with antiviral activity (PMID 3162334). PMID 14872030 c.-88G>T was more frequent in 40 unrelated Japanese patients with subacute sclerosing panencephalitisis (associated with CNS infection with measles virus), than in 90 controls (0.42 in patients vs 0.29 in controls). Variant c.-88G>T results increased MX1 expression, the authors suggest that MX1 may paradoxically enable persistence of the virus in the CNS by attenuating viral gene expression and preventing complete immunologic clearance. PMID 21935451 concluded that genetic variation in the interferon response pathway is associated with risk for symptomatic West Nile viru infection and disease progression. Preprint https://doi.org/10.1101/2020.05.04.075911 Reports that rs35074065 of TMPRSS2 results in increased expression of the nearby gene MX1. Sources: Literature |
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| COVID-19 research v0.214 | TMPRSS2 | Sarah Leigh changed review comment from: Preprint https://doi.org/10.1101/2020.05.04.075911 reports rs35074065 of TMPRSS2 results in the overexpression of both TMPRSS2 and a nearby gene MX1. rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.; to: Preprint https://doi.org/10.1101/2020.05.04.075911 reports rs35074065 of TMPRSS2 results in the overexpression of both TMPRSS2 and a nearby gene MX1. rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele of rs35074065, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G variant viral Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.204 | TMPRSS2 | Sarah Leigh reviewed gene: TMPRSS2: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.1101/2020.05.04.075911; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.203 | TMPRSS2 | Sophie Hambleton reviewed gene: TMPRSS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | TMPRSS2 | Rebecca Foulger commented on gene: TMPRSS2: Preprint http://biorxiv.org/cgi/content/short/2020.04.23.057190 analysed coding region variants in TMPRSS2 and the eQTL variants which may affect gene experssion. They suggest that lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations. In particular, we found that the regulatory region variant rs35074065 is associated with high expression of TMPRSS2 (but lower expression of MX1). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | ACE2 | Rebecca Foulger commented on gene: ACE2: Preprint https://www.biorxiv.org/content/10.1101/2020.04.24.050534v1 conclude that higher expression of ACE2 facilitated by natural variations (with different frequencies in different populations) results in ACE2 homo-dimerization which is disadvantageous for TMPRSS2 mediated cleavage of ACE2. They propose that monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.165 | 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 v0.148 | TMPRSS2 | Rebecca Foulger Classified gene: TMPRSS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.148 | TMPRSS2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green on this research panel: Known mechanisms for involvement in viral infection (including proteolytic cleavage of the viral receptor, ACE2) plus variants identified in preprints as candidates for COVID-19 severity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.148 | TMPRSS2 | Rebecca Foulger Gene: tmprss2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.147 | TMPRSS2 | Rebecca Foulger commented on gene: TMPRSS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.147 | TMPRSS2 | Rebecca Foulger Publications for gene: TMPRSS2 were set to 31488196; 32142651; 24227843 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.146 | TMPRSS2 | Rebecca Foulger Publications for gene: TMPRSS2 were set to 31488196 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.111 | 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 v0.111 | TMPRSS2 | Catherine Snow Classified gene: TMPRSS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.111 | TMPRSS2 | Catherine Snow Gene: tmprss2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COVID-19 research v0.110 | TMPRSS2 |
Catherine Snow gene: TMPRSS2 was added gene: TMPRSS2 was added to Viral susceptibility. Sources: Literature Mode of inheritance for gene: TMPRSS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMPRSS2 were set to 31488196 Review for gene: TMPRSS2 was set to AMBER Added comment: PMID: 31488196 - Host susceptibility to severe influenza A virus infection, this paper reviews genes involved and identified TMPRSS2. This gene has also been identified in this preprint - ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy https://doi.org/10.1101/2020.03.30.20047878 Sources: Literature |
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