VWA1

Chr 1AR

von Willebrand factor A domain containing 1

Also known as: HMNMYO, HMNR7, WARP

NCBI Gene: 64856ENSG00000179403UniProt: Q6PCB0

VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

Primary Disease Associations & Inheritance

Neuronopathy, distal hereditary motor, autosomal recessive 7MIM #619216
AR
UniProtNeuronopathy, hereditary motor, autosomal recessive 7
0
Active trials
146
Pathogenic / LP
337
ClinVar variants
10
Pubs (1 yr)
-0.1
Missense Z
1.07
LOEUF
Clinical Summary— VWA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
146 Pathogenic / Likely Pathogenic· 152 VUS of 337 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.005
Z-score 1.43
OE 0.51 (0.26–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.15Z-score
OE missense 1.03 (0.92–1.15)
219 obs / 212.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.26–1.07)
0≤0.351.4
Missense OE1.03 (0.92–1.15)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 5 / 9.9Missense obs/exp: 219 / 212.9Syn Z: 0.32
GOFDN
DN
0.7326th %ile
GOF
0.83top 10%
LOF
0.2582th %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

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic20
VUS152
Likely Benign21
Benign12
Conflicting6
126
Pathogenic
20
Likely Pathogenic
152
VUS
21
Likely Benign
12
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
122
1
126
Likely Pathogenic
11
0
9
0
20
VUS
2
122
27
1
152
Likely Benign
0
9
2
10
21
Benign
0
3
5
4
12
Conflicting
—6
Total1613416516337

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

View in ClinVar →

VWA1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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