CLEC4A
protein-codingC-type lectin domain family 4 member A, the group of C-type lectin domain containing|CD molecules
Gene summary
This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]
- CLECSF6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.0 kbGenCC 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 CLEC4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016184.4. 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 | 0 | |||||
| missense | 30 | 6 | 36 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 32 | 6 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057268.1 | 6 | MANE Select | |
| Ensembl | ENSP00000229332.5 | 6 | MANE Select | |
| RefSeq | NP_919429.2 | 5 | Standard | |
| RefSeq | NP_919430.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Dectin-2 family
- C-type lectin receptors (CLRs)
- Innate Immune System
- Immune System
Biological Process
- negative regulation of cytokine production
- stimulatory C-type lectin receptor signaling pathway
- adaptive immune response
- plasmacytoid dendritic cell antigen processing and presentation
- cell adhesion
Molecular Function
- transmembrane signaling receptor activity
- calcium ion binding
- mannose binding
- carbohydrate binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000229332
- Coding exons
- 6
- Length
- 14976
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125747
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.545 | 107 | 124 | 0.862 | 0.00000620 | 1571 |
| Missense (PolyPhen) | 25 | 28.052 | 0.89121 | 396 | ||
| Synonymous | -0.484 | 48 | 43.9 | 1.09 | 0.00000223 | 418 |
| Loss of Function | 0.849 | 8 | 11.0 | 0.724 | 5.65e-7 | 135 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner (PubMed:27015765). Involved in regulating immune reactivity (PubMed:18258799, PubMed:10438934). Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13 (PubMed:18258799, PubMed:20530286). In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production (PubMed:18258799). May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation (PubMed:10438934). {ECO:0000269|PubMed:10438934, ECO:0000269|PubMed:18258799, ECO:0000269|PubMed:20530286, ECO:0000269|PubMed:27015765}.;
Recessive Scores
- pRec
- 0.0810
Intolerance Scores
- LoFtool
- 0.991
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.144
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |