CLEC3A

Chr 16

C-type lectin domain family 3 member A

Also known as: CLECSF1

NCBI Gene: 10143 ENSG00000166509 UniProt: O75596 OMIM: 613588

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable carbohydrate binding activity. Predicted to be involved in ossification. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— CLEC3A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 VUS of 9 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.000

Z-score -1.22

OE 1.42 (0.92–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.65Z-score

OE missense 1.69 (1.50–1.89)

198 obs / 117.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.42 (0.92–1.91)

0≤0.351.4

Missense OE?1.69 (1.50–1.89)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

LoF obs/exp: 14 / 9.9Missense obs/exp: 198 / 117.4Syn Z: -2.22

This gene — mechanism propensity

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

9 submitted variants in ClinVar

ClinVar

Classification Summary

VUS8

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	8	8
Likely Benign	0	0
Benign	0	0
Total	8	8

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 77) ClinVar copy-number / structural variants overlap CLEC3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →