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COVID-19 research

Gene: CLEC4M

Amber List (moderate evidence)

CLEC4M (C-type lectin domain family 4 member M)
EnsemblGeneIds (GRCh38): ENSG00000104938
EnsemblGeneIds (GRCh37): ENSG00000104938
OMIM: 605872, Gene2Phenotype
CLEC4M is in 2 panels

3 reviews

Alison Coffey (Illumina Clinical Services Laboratory, Illumina Inc.)

Red List (low evidence)

Mode of inheritance
Unknown

Publications

Sarah Leigh (Genomics England Curator)

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.
Created: 11 Jun 2020, 6:10 p.m. | Last Modified: 12 Jun 2020, 10:11 a.m.
Panel Version: 1.17

Rebecca Foulger (Genomics England curator)

Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 2 Jun 2020, 1:53 p.m. | Last Modified: 2 Jun 2020, 1:53 p.m.
Panel Version: 1.1

Details

Mode of Inheritance
Unknown
Sources
Phenotypes
  • SARS infection, protection against, 605872
OMIM
605872
Clinvar variants
Variants in CLEC4M
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Jun 2020, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CLEC4M were set to

2 Jun 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: CLEC4M was added gene: CLEC4M was added to COVID-19 research. Sources: OMIM,Expert list,Expert Review Amber Mode of inheritance for gene: CLEC4M was set to Unknown Phenotypes for gene: CLEC4M were set to SARS infection, protection against, 605872