VKORC1: Vitamin K Epoxide Reductase Complex Subunit 1
Key regulator of vitamin K recycling and target of warfarin anticoagulation
Gene Information Card
| Symbol | VKORC1 |
|---|---|
| Full Name | Vitamin K Epoxide Reductase Complex Subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 79001 ncbi.nlm.nih.gov/gene/79001 |
| Ensembl ID | ENSG00000167397 |
| UniProt ID | Q9BQB6 |
| OMIM ID | 608547 |
| HGNC ID | 18963 |
| Aliases | VKOR, VKORC1A, MST134, MSTP134 |
Description
VKORC1 encodes the catalytic subunit of the vitamin K epoxide reductase (VKOR) complex, which reduces vitamin K 2,3-epoxide to vitamin K hydroquinone, a critical cofactor for the gamma-carboxylation of vitamin K-dependent proteins, including clotting factors II, VII, IX, and X. This enzyme is the molecular target of warfarin, a widely used oral anticoagulant. Genetic variants in VKORC1 influence warfarin sensitivity and resistance, affecting dosing requirements and risk of bleeding or thrombosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warfarin sensitivity | Reduced VKORC1 activity due to promoter polymorphisms (e.g., -1639G>A) decreases vitamin K recycling, enhancing warfarin effect and requiring lower doses. | ClinVar, NCBI |
| Warfarin resistance | Missense mutations (e.g., p.Val66Met, p.Arg58Gly) reduce warfarin binding affinity, requiring higher doses for anticoagulation. | ClinVar, OMIM |
| Vitamin K-dependent clotting factor deficiency 2 (VKCFD2) | Biallelic loss-of-function mutations impair vitamin K recycling, leading to combined deficiency of factors II, VII, IX, X and bleeding diathesis. | OMIM #607473 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 6.8 | Medium |
| Heart | 3.2 | Low |
| Lung | 2.1 | Low |
| Brain | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocyte line, high expression |
| HEK293 | 8.7 | Embryonic kidney line, moderate |
| A549 | 4.1 | Lung carcinoma line, low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.-1639G>A (rs9923231) | Promoter SNP | ~40% in Asians, ~15% in Europeans | Reduced promoter activity, increased warfarin sensitivity |
| c.196G>A (p.Val66Met) | Missense | Rare | Warfarin resistance, reduced warfarin binding |
| c.172A>G (p.Arg58Gly) | Missense | Rare | Warfarin resistance |
| c.106C>T (p.Arg36Trp) | Missense | Rare | Loss of function, VKCFD2 |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or nonsense mutations (e.g., p.Arg36Trp) impair vitamin K epoxide reductase activity, causing VKCFD2 with bleeding tendency.
Gain of Function (GOF)
Not described; increased activity would theoretically reduce warfarin effect but no confirmed gain-of-function variants reported.
Dominant Negative (DN)
Not established; warfarin resistance mutations are typically recessive or co-dominant in effect.
View complete mutation data：
Gene Ontology (GO)
| • retinoid binding (GO:0005501) | • endoplasmic reticulum (GO:0005783) |
| • isomerase activity (GO:0016853) | • vitamin K epoxide reductase (warfarin-sensitive) activity (GO:0047053) |
| • blood coagulation (GO:0007596) |
Pathways
• Vitamin K cycle (Reactome: R-HSA-6806667)
• Gamma-carboxylation of vitamin K-dependent proteins (Reactome: R-HSA-159854)
• Warfarin pharmacodynamics (PharmGKB: PA166104994)
Protein Summary
VKORC1 is a small integral membrane protein (163 amino acids) located in the endoplasmic reticulum. It contains four transmembrane domains and a conserved active site cysteine motif (Cys132-Cys135) essential for vitamin K epoxide reduction. The protein forms the catalytic core of the VKOR complex, which also includes accessory subunits such as VKORC1L1. Warfarin inhibits VKORC1 by binding to the reduced form of the enzyme, preventing vitamin K recycling and thereby reducing clotting factor activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VKORC1L1 Knockout HEK293 Cell Line | EDJ-KQ16102 | Human | 154807 | Details Get a Quote |
| VKORC1L1 Knockout A-549 Cell Line | EDJ-KQ47254 | Human | 154807 | Details Get a Quote |
| VKORC1L1 Knockout HCT 116 Cell Line | EDJ-KQ47255 | Human | 154807 | Details Get a Quote |
| VKORC1L1 Knockout HeLa Cell Line | EDJ-KQ47256 | Human | 154807 | Details Get a Quote |
| VKORC1 Knockout HEK293 Cell Line | EDJ-KQ51651 | Human | 79001 | Details Get a Quote |
| VKORC1 Knockout HeLa Cell Line | EDJ-KQ57126 | Human | 79001 | Details Get a Quote |
| VKORC1 Knockout A-549 Cell Line | EDJ-KQ65639 | Human | 79001 | Details Get a Quote |
| VKORC1 Knockout HCT 116 Cell Line | EDJ-KQ74062 | Human | 79001 | Details Get a Quote |
| VKORC1 Knockout HAP1 Cell Line | EDC08035 | Human | 79001 | Details Get a Quote |
