CLEC4M

protein-coding

C-type lectin domain family 4 member M, the group of CD molecules

Gene summary

This gene encodes a C-type lectin that functions in cell adhesion and pathogen recognition. This receptor recognizes a wide range of evolutionarily divergent pathogens with a large impact on public health, including tuberculosis mycobacteria, and viruses including Ebola, hepatitis C, HIV-1, influenza A, West Nile virus and the SARS-CoV acute respiratory syndrome coronavirus. The protein is organized into four distinct domains: a C-terminal carbohydrate recognition domain, a flexible tandem-repeat neck domain of variable length, a transmembrane region and an N-terminal cytoplasmic domain involved in internalization. This gene is closely related in terms of both sequence and function to a neighboring gene, CD209 (Gene ID: 30835), also known as DC-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression in endothelial cells of the liver, lymph node and placenta. Polymorphisms in the tandem repeat neck domain are associated with resistance to SARS infection. [provided by RefSeq, May 2020]

Previous symbols:

CD209L
CD299

MANE transcript

NM_014257.5

Inheritance

—

ClinVar variants

U:29B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr19:7,763,210-7,769,605

External References & Databases

Ensembl (ENSG00000104938)

Transcript & Mutation Effects

hg38 • Region Span ~6.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLEC4M variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014257.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense			29 clinvar	3 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	7	0	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014257.5	RefSeq	NP_055072.3	7	MANE Select
ENST00000327325.10	Ensembl	ENSP00000316228.4	7	MANE Select
NM_001144911.2	RefSeq	NP_001138383.1	5	Standard
NM_001416369.1	RefSeq	NP_001403298.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phagosome - Homo sapiens (human)
C-type lectin receptor signaling pathway - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
Measles - Homo sapiens (human)
Human Complement System

Biological Process

adaptive immune response
endocytosis
leukocyte cell-cell adhesion
cell-cell recognition
modulation by virus of host morphology or physiology

Molecular Function

virus receptor activity
mannose binding
carbohydrate binding
ICAM-3 receptor activity
signaling receptor activity

Cellular Component

extracellular region
cytoplasm
integral component of plasma membrane
membrane
host cell

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327325
Coding exons: 7
Length: 6457
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.916	166	203	0.819	0.0000114	2586
Missense (PolyPhen)		91	111.11	0.81903		1493
Synonymous	-0.0652	90	89.2	1.01	0.00000551	766
Loss of Function	1.18	12	17.3	0.693	7.51e-7	212

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates. {ECO:0000269|PubMed:11257134}.; FUNCTION: (Microbial infection) Acts as an attachment receptor for Hepatitis C virus. {ECO:0000269|PubMed:15371595, ECO:0000269|PubMed:16816373}.; FUNCTION: (Microbial infection) Acts as an attachment receptor for Human coronavirus 229E. {ECO:0000269|PubMed:17037540}.; FUNCTION: (Microbial infection) Acts as an attachment receptor for Influenzavirus. {ECO:0000269|PubMed:21191006}.; FUNCTION: (Microbial infection) Acts as an attachment receptor for West-nile virus. {ECO:0000269|PubMed:15479853}.; FUNCTION: (Microbial infection) Acts as an attachment receptor for Marburg virus glycoprotein. {ECO:0000269|PubMed:15479853}.;

Intolerance Scores

LoFtool: 0.909
RVIS EVS: 0.07
RVIS percentile EVS: 58.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.358

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium