CLEC6A
protein-codingC-type lectin domain containing 6A, the group of C-type lectin domain containing
Gene summary
The protein encoded by this gene is a type II membrane receptor with an extracellular C-type lectin-like domain fold. The extracellular portion binds structures with a high mannose content and has been shown to recognize several pathogens, including C. elegans, S. cerevisiae, M. tuberculosis, C. neoformans, and house dust mite. When stimulated, the encoded protein initiates signalling through the CARD9-Bcl10-Malt1 pathway, leading to the induction of cytokines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]
- CLECSF10
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.4 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 CLEC6A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001007033.2. 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 | 23 | 4 | 27 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 23 | 4 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001007034.1 | 6 | MANE Select | |
| Ensembl | ENSP00000371505.3 | 6 | MANE Select | |
| RefSeq | NP_001304928.1 | 5 | Standard | |
| Ensembl | ENSP00000811294.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- C-type lectin receptor signaling pathway - Homo sapiens (human)
- Ebola Virus Pathway on Host
- Ebola Virus Pathway on Host
- Dectin-2 family
- C-type lectin receptors (CLRs)
Biological Process
- stimulatory C-type lectin receptor signaling pathway
- adaptive immune response
- positive regulation of I-kappaB kinase/NF-kappaB signaling
- innate immune response
- positive regulation of cytokine secretion
Molecular Function
- calcium ion binding
- mannose binding
- carbohydrate binding
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382073
- Coding exons
- 6
- Length
- 22405
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125746
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0265 | 104 | 103 | 1.01 | 0.00000434 | 1377 |
| Missense (PolyPhen) | 25 | 27.38 | 0.91306 | 377 | ||
| Synonymous | 0.131 | 33 | 34.0 | 0.971 | 0.00000146 | 354 |
| Loss of Function | 0.472 | 10 | 11.7 | 0.851 | 5.01e-7 | 133 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000066 | 0.000046 | rare |
| European (Non-Finnish) | 0.000090 | 0.000088 | rare |
| South Asian | 0.00019 | 0.00016 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds high-mannose carbohydrates in a Ca(2+)-dependent manner (PubMed:28652405). Functional receptor for alpha-mannans on C.albicans hypheas. Plays an important role in the host defense against C.albicans infection by inducing TH17 cell differentiation. Recognizes also, in a mannose-dependent manner, allergens from house dust mite and fungi, by promoting cysteinyl leukotriene production. Recognizes soluble elements from the eggs of Shistosoma mansoni altering adaptive immune responses. Transduces signals through an Fc receptor gamma chain /FCER1G and Syk-CARD9-NF-kappa-B-dependent pathway (By similarity). {ECO:0000250|UniProtKB:Q9JKF4, ECO:0000269|PubMed:28652405}.;
Recessive Scores
- pRec
- 0.0596
Intolerance Scores
- RVIS EVS
- 0.95
- RVIS percentile EVS
- 89.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0696
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |