CLEC4M C-type lectin domain family 4 member M [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLEC4Mprovided by HGNC
Official Full Name: C-type lectin domain family 4 member Mprovided by HGNC
Primary source: HGNC:HGNC:13523
See related: Ensembl:ENSG00000104938 MIM:605872; AllianceGenome:HGNC:13523
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD299; LSIGN; CD209L; L-SIGN; DCSIGNR; HP10347; DC-SIGN2; DC-SIGNR
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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 prognosis.
Expression: Biased expression in liver (RPKM 15.4), lymph node (RPKM 9.8) and 3 other tissues See more
Orthologs: all
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Genomic context

Location:: 19p13.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (7763243..7769605)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (7764262..7770624)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (7828129..7834491)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Relationship between the Number of Repeats in the Neck Regions of L-SIGN and Augmented Virus Replication and Immune Responses in Dengue Hemorrhagic Fever.
Title: Relationship between the Number of Repeats in the Neck Regions of L-SIGN and Augmented Virus Replication and Immune Responses in Dengue Hemorrhagic Fever.
ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy-Implications for SARS-CoV-2 Placental Infection.
Title: ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy-Implications for SARS-CoV-2 Placental Infection.
CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma.
Title: CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma.
CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
Title: The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
heterozygous VNTR genotypes 57 and 67 of CLEC4M were highly enriched and are the most likely mechanism through which CLEC4M contributes to disease in the Swedish type 1 VWD population
Title: Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients.
DC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.
Title: DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis.
the neck domains of DC-SIGN and DC-SIGNR can contribute to the different functions of these receptors by presenting the sugar-binding sites in different contexts.
Title: Oligomerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR: Sequence variation and stability differences.
Together, these studies confirm a role for C-type lectin receptors DC-SIGN and L-SIGN as attachment factors and entry receptors for human metapneumovirus infection.
Title: DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans.
DC-SIGNR VNTR and DC-SIGN VNTR were not associated with the risk of pulmonary tuberculosis in a sample of Iranian population
Title: Association of DC-SIGN and DC-SIGNR Repeat Regions with Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeastern Iran.
CD209L variation may influence susceptibility to HIV-1, response to treatment, and disease progression.
Title: Association of CD209L tandem repeats polymorphism with susceptibility to human immunodeficiency virus-1 infection, disease progression, and treatment outcomes: a Moroccan cohort study.

Submit: New GeneRIF Correction See all GeneRIFs (74)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR in combination with binding studies reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides of HIV-1 gp120	PubMed
	env	HIV-1 gp120 binds to a membrane-associated mannose-binding lectin in a CD4-independent manner	PubMed
	env	L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

RH65100 (e-PCR)
- UniSTS:85320

PMC140574P1 (e-PCR)
- UniSTS:270942

PMC140574P2 (e-PCR)
- UniSTS:270943

D1S1423 (e-PCR)
- UniSTS:149619

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables D-mannose binding	IBA Inferred from Biological aspect of Ancestor more info
enables ICAM-3 receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables calcium-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables carbohydrate binding	NAS Non-traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables pattern recognition receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables peptide antigen binding	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables virion binding	TAS Traceable Author Statement more info	PubMed
enables virus receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables virus receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in antigen processing and presentation	NAS Non-traceable Author Statement more info	PubMed
involved_in cell-cell recognition	TAS Traceable Author Statement more info	PubMed
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in intracellular transport of virus	TAS Traceable Author Statement more info	PubMed
involved_in leukocyte cell-cell adhesion	NAS Non-traceable Author Statement more info	PubMed
involved_in peptide antigen transport	NAS Non-traceable Author Statement more info	PubMed
involved_in receptor-mediated endocytosis of virus by host cell	NAS Non-traceable Author Statement more info	PubMed
involved_in receptor-mediated virion attachment to host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in symbiont entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in viral genome replication	NAS Non-traceable Author Statement more info	PubMed
involved_in virion attachment to host cell	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in host cell	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: C-type lectin domain family 4 member M

Names: CD209 antigen-like protein 1; CD299 antigen; DC-SIGN-related protein; dendritic cell-specific ICAM-3-grabbing non-integrin 2; liver/lymph node-specific ICAM-3 grabbing non-integrin; mannose binding C-type lectin DC-SIGNR

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029190.1 RefSeqGene

Range

5095..11457

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001144911.2 → NP_001138383.1 C-type lectin domain family 4 member M isoform 3

See identical proteins and their annotated locations for NP_001138383.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences in the coding region, compared to variant 1, one of which results in a translational frameshift. The resulting protein (isoform 3) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AB015629, BC038851

Consensus CDS

CCDS59348.1

UniProtKB/Swiss-Prot

Q9H2X3

Related

ENSP00000471125.1, ENST00000596363.5

Conserved Domains (1) summary

cl02432
Location:240 → 284

CLECT; C-type lectin (CTL)/C-type lectin-like (CTLD) domain
NM_001416369.1 → NP_001403298.1 C-type lectin domain family 4 member M isoform 6

Status: REVIEWED

Source sequence(s)

AC008812

UniProtKB/TrEMBL

A0A7P0MMK7, E7ENS9

Related

ENSP00000351954.6, ENST00000359059.10
NM_001416370.1 → NP_001403299.1 C-type lectin domain family 4 member M isoform 7

Status: REVIEWED

Source sequence(s)

AC008812

UniProtKB/TrEMBL

E7ENS9
NM_014257.5 → NP_055072.3 C-type lectin domain family 4 member M isoform 1

See identical proteins and their annotated locations for NP_055072.3

Status: REVIEWED

Source sequence(s)

BC038851

Consensus CDS

CCDS12187.1

UniProtKB/Swiss-Prot

A6NKI4, A8K8B3, Q69F40, Q969M4, Q96QP3, Q96QP4, Q96QP5, Q96QP6, Q9BXS3, Q9H2Q9, Q9H2X3, Q9H8F0, Q9Y2A8

UniProtKB/TrEMBL

E7ENS9

Related

ENSP00000316228.4, ENST00000327325.10

Conserved Domains (2) summary

cd03590
Location:268 → 391

CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)

cl19219
Location:140 → 251

DUF342; Protein of unknown function (DUF342)

RNA

NR_026707.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences in the coding region, compared to variant 1. This variant 4 replaces NM_214677 and is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AA431250, AY042235, BC038851, BX102225, DB048428
NR_026708.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) has multiple differences in the coding region, compared to variant 1. This variant 5 replaces NM_214678 and is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AA431250, AY042236, BC038851, BX102225, DB048428

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

7763243..7769605

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

7764262..7770624

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001144904.2: Suppressed sequence

Description

NM_001144904.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144905.2: Suppressed sequence

Description

NM_001144905.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144906.2: Suppressed sequence

Description

NM_001144906.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144907.2: Suppressed sequence

Description

NM_001144907.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144908.2: Suppressed sequence

Description

NM_001144908.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144909.2: Suppressed sequence

Description

NM_001144909.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_001144910.2: Suppressed sequence

Description

NM_001144910.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome in the number of repeats within the neck domain.
NM_214675.1: Suppressed sequence

Description

NM_214675.1: This RefSeq was permanently suppressed because it is redundant.
NM_214676.1: Suppressed sequence

Description

NM_214676.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NR_026709.2: Suppressed sequence

Description

NR_026709.2: This RefSeq was removed because it represents a haplotype that differs from the reference genome.