CLEC3A

Chr 16

C-type lectin domain family 3 member A

Also known as: CLECSF1

The CLEC3A protein binds carbohydrates and promotes cell adhesion to laminin-332 and fibronectin in the extracellular space, where it contributes to bone ossification. Loss-of-function mutations cause autosomal recessive osteosclerotic metaphyseal dysplasia, a skeletal disorder characterized by increased bone density and metaphyseal abnormalities. The extremely low pLI score indicates this gene is highly tolerant to loss-of-function variants in the general population.

Summary from RefSeq, UniProt
0
Active trials
8
Pubs (1 yr)
30
P/LP submissions
P/LP missense
1.91
LOEUF
DN
Mechanism· predicted
Clinical SummaryCLEC3A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 46 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.91LOEUF
pLI 0.000
Z-score -1.22
OE 1.42 (0.921.91)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.65Z-score
OE missense 1.69 (1.501.89)
198 obs / 117.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.42 (0.921.91)
00.351.4
Missense OE1.69 (1.501.89)
00.61.4
Synonymous OE1.42
01.21.6
LoF obs/exp: 14 / 9.9Missense obs/exp: 198 / 117.4Syn Z: -2.22
DN
0.6453th %ile
GOF
0.5465th %ile
LOF
0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

83 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS46
Likely Benign5
27
Pathogenic
3
Likely Pathogenic
46
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
Likely Pathogenic
3
VUS
46
Likely Benign
5
Benign
0
Total81

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CLEC3A · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →