VWF
Chr 12ADARvon Willebrand factor
Also known as: F8VWF, VWD
This gene encodes von Willebrand factor, a glycoprotein that promotes platelet adhesion at sites of vascular injury and serves as a chaperone for coagulation factor VIII. Mutations cause von Willebrand disease, the most common inherited bleeding disorder, with subtypes including type 1 (mild bleeding), type 2 variants (2A, 2B, 2M, 2N with specific functional defects), and type 3 (severe bleeding with absence of von Willebrand factor). The gene shows high tolerance to loss-of-function variants and inheritance can be autosomal dominant or autosomal recessive depending on the subtype.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative 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.
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.
Literature Evidence
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
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 25 | 2 | 20 | 0 | 47 |
Likely Pathogenic | 17 | 13 | 6 | 0 | 36 |
VUS | 2 | 322 | 19 | 13 | 356 |
Likely Benign | 0 | 4 | 16 | 26 | 46 |
Benign | 0 | 0 | 54 | 1 | 55 |
Conflicting | — | 9 | |||
| Total | 44 | 341 | 115 | 40 | 549 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
VWF · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Cushing's Syndrome Before and After Treatment (CORRECT)
RECRUITINGA Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
NOT YET RECRUITINGFontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
RECRUITINGEffect of Sirolimus on Molecular Alterations in Cerebral Aneurysms
RECRUITINGGenotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)
RECRUITINGItalian Digital Primary Cardiovascular Prevention Study
ACTIVE NOT RECRUITINGA Study to Learn More About the Treatment of People With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Who Received Recombinant ADAMTS13 (rADAMTS13) as Part of the Early Access Program
NOT YET RECRUITINGEndoNAFLD: Relationship Between Fatty Liver Disease and Cardiovascular Diseases
RECRUITINGExternal Resources
Links to major genomics databases and tools