VKORC1
Chr 16ARADvitamin K epoxide reductase complex subunit 1
Also known as: EDTP308, MST134, MST576, VKCFD2, VKOR
The protein is the catalytic subunit of vitamin K epoxide reductase complex, which reduces inactive vitamin K 2,3-epoxide to active vitamin K required for gamma-carboxylation of clotting factors and normal blood coagulation. Mutations cause combined deficiency of vitamin K-dependent clotting factors type 2, presenting with bleeding disorders that can manifest in infancy or childhood. The condition follows autosomal recessive inheritance.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
VKORC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools