CLEC3B

Chr 3AD

C-type lectin domain family 3 member B

Also known as: MCDR4, TN, TNA

NCBI Gene: 7123ENSG00000163815UniProt: P05452OMIM: 187520

The CLEC3B protein (tetranectin) binds calcium and plasminogen, functions in bone mineralization, and plays a role in retinal function. Mutations cause retinal macular dystrophy 4 with autosomal dominant inheritance. The gene shows tolerance to loss-of-function variants (pLI 0.002, LOEUF 1.34), suggesting the pathogenic variants may work through other mechanisms.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.341 OMIM phenotype
Clinical Summary— CLEC3B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 28 VUS of 37 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
1.34LOEUF
pLI 0.002
Z-score 0.94
OE 0.64 (0.33–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.33Z-score
OE missense 0.67 (0.56–0.80)
87 obs / 129.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.33–1.34)
0≤0.351.4
Missense OE0.67 (0.56–0.80)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 5 / 7.8Missense obs/exp: 87 / 129.8Syn Z: 1.05
DN
0.6455th %ile
GOF
0.6735th %ile
LOF
0.2385th %ile

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

GOFprediction above median
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

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS28
7
Pathogenic
1
Likely Pathogenic
28
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
6
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
26
2
0
28
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0279036

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

View in ClinVar →

Protein Context — Lollipop Plot

CLEC3B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients