CLEC10A

Chr 17

C-type lectin domain containing 10A

Also known as: CD301, CLECSF13, CLECSF14, DC-ASGPR, HML, HML2, MGL

The protein is a C-type lectin receptor that recognizes specific sugar structures on cell surfaces and plays a critical role in immune cell communication and antigen presentation by dendritic cells. Mutations in this gene cause autosomal recessive ataxia-telangiectasia-like disorder, characterized by progressive cerebellar ataxia, immunodeficiency, and increased cancer susceptibility typically beginning in early childhood. This gene is not highly constrained against loss-of-function variants, and the disorder primarily affects the nervous and immune systems.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.14
Clinical SummaryCLEC10A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 36 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.14LOEUF
pLI 0.000
Z-score 1.18
OE 0.67 (0.411.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.36Z-score
OE missense 0.92 (0.811.05)
154 obs / 167.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.411.14)
00.351.4
Missense OE0.92 (0.811.05)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 10 / 14.9Missense obs/exp: 154 / 167.1Syn Z: 0.93
DN
0.81top 10%
GOF
0.72top 25%
LOF
0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS36
Likely Benign5
Benign1
18
Pathogenic
1
Likely Pathogenic
36
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
29
7
0
36
Likely Benign
0
5
0
0
5
Benign
0
1
0
0
1
Total03526061

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CLEC10A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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