VWA3B

Chr 2AR

von Willebrand factor A domain containing 3B

Also known as: SCAR22

NCBI Gene: 200403ENSG00000168658UniProt: Q502W6OMIM: 614884

The protein contains a von Willebrand factor type A domain and functions in cellular processes including transcription, DNA repair, ribosomal transport, membrane transport, and proteasome activity. Mutations cause spinocerebellar ataxia, autosomal recessive 22, which follows autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive disease pattern.

OMIMResearchSummary from RefSeq, OMIM
MultiplemechanismARLOEUF 0.941 OMIM phenotype
Clinical Summary— VWA3B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 147 VUS of 211 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
0.94LOEUF
pLI 0.000
Z-score 1.97
OE 0.75 (0.60–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.26Z-score
OE missense 0.97 (0.91–1.04)
678 obs / 697.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.60–0.94)
0≤0.351.4
Missense OE0.97 (0.91–1.04)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 52 / 69.7Missense obs/exp: 678 / 697.2Syn Z: 0.34
DN
0.6065th %ile
GOF
0.6540th %ile
LOF
0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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
LOF33% of P/LP variants are LoF

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

211 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic6
VUS147
Likely Benign27
Benign6
9
Pathogenic
6
Likely Pathogenic
147
VUS
27
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
8
0
9
Likely Pathogenic
5
0
1
0
6
VUS
10
131
6
0
147
Likely Benign
0
16
4
7
27
Benign
1
2
3
0
6
Total16150227195

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

View in ClinVar →

Protein Context — Lollipop Plot

VWA3B · 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 2 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