Protein / target

Vitamin K epoxide reductase complex subunit 1

VKORC1Q9BQB6Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
8
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Vitamin-K-epoxide reductase (warfarin-insensitive) activity

Strongest disease association

Hereditary combined deficiency of vitamin K-dependent clotting factors

Genetic literature evidence · score 0.80

Therapeutic maturity

Clinically validated target

6 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

6 approved · 1 in clinical development

8 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development

Subcellular location

Endoplasmic reticulum membrane
Domains and Gene Ontology detail (11)

Gene Ontology

  • Cendoplasmic reticulum
  • Cendoplasmic reticulum lumen
  • Cendoplasmic reticulum membrane
  • Fquinone binding
  • Fvitamin-K-epoxide reductase (warfarin-insensitive) activity
  • Fvitamin-K-epoxide reductase (warfarin-sensitive) activity
  • Pblood coagulation
  • Pbone development
  • Ppeptidyl-glutamic acid carboxylation
  • Pvitamin K metabolic process
  • Pxenobiotic metabolic process

163 aa · 18 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

HaemostasisUniProt · GOMetabolic enzyme activityGO
View supporting evidence

Haemostasis

  • ·Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (…
  • ·blood coagulation

Metabolic enzyme activity

  • ·vitamin K metabolic process
  • ·xenobiotic metabolic process
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GGCXCYP2C9CYP4F2VKORC1…NQO1CYP2C19PROS1MGPF2ABCC6VKORC1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Acenocoumarol
Narrow target profileApprovedInhibitor

Vitamin k epoxide reductase complex subunit 1 isoform 1 inhibitor

Appears in clinical studies involving Recurrent thrombophlebitis, thrombotic disease, pulmonary embolism, cervical artery dissection

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

Hereditary combined deficiency of vitamin K-dependent clotting factors0.80

Genetic literature · overall 0.72

vitamin K-dependent clotting factors, combined deficiency of, type 20.80

Genetic literature · overall 0.72

venous thromboembolism0.55

Genetic · overall 0.45

thrombotic disease0.24

Genetic · overall 0.60

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

atrial fibrillation1.00

Clinical · overall 0.61

pulmonary embolism0.91

Clinical · overall 0.56

Recurrent thrombophlebitis0.89

Clinical · overall 0.54

myocardial infarction0.85

Clinical · overall 0.52

Venous thrombosis0.80

Clinical · overall 0.49

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

stroke disorder0.50

Clinical

Show all associations
Hereditary combined deficiency of vitamin K-dependent clotting factors0.72
vitamin K-dependent clotting factors, combined deficiency of, type 20.72
atrial fibrillation0.61
thrombotic disease0.60
pulmonary embolism0.56
Recurrent thrombophlebitis0.54
myocardial infarction0.52
stroke disorder0.50
Venous thrombosis0.49
venous thromboembolism0.45

Open Targets ranks 862 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 7 total

PHENPROCOUMONApproval

Recurrent thrombophlebitis · thrombotic disease · hemorrhage

PHENINDIONEApproval

Recurrent thrombophlebitis · blood coagulation disease · pulmonary embolism

TECARFARINPhase 3

thrombotic disease

DICUMAROLApproval

Recurrent thrombophlebitis · hemorrhagic disease · thrombotic disease

ACENOCOUMAROLApproval

Recurrent thrombophlebitis · thrombotic disease · pulmonary embolism

WARFARINApproval

Recurrent thrombophlebitis · atrial fibrillation · thrombotic disease

WARFARIN SODIUMApproval

atrial fibrillation · Thromboembolism · Venous thrombosis

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Safety liabilities

over-anticoagulationhemorrhageHemorrhageadverse eventsbleeding

Clinical trials

8

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

thrombotic diseaseWell supported
0.77
agreement 0.660.87
Clinical74%Genetic26%Literature0%

Open Targets aggregate 0.60 · 3 independent evidence families

atrial fibrillationWell supported
0.76
agreement 0.600.91
Clinical95%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

venous thromboembolismWell supported
0.76
agreement 0.650.86
Genetic54%Clinical45%Literature1%

Open Targets aggregate 0.45 · 3 independent evidence families

Hereditary combined deficiency of vitamin K-dependent clotting factorsModerately supported
0.70
agreement 0.570.84
Genetic literature79%Animal model21%Geneticdup

Open Targets aggregate 0.72 · 2 independent evidence families · 1 not counted as duplicate

pulmonary embolismModerately supported
0.69
agreement 0.530.84
Clinical97%Literature3%

Open Targets aggregate 0.56 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

1

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2003-07-01
    Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

    The New England journal of medicine · 2003 · 1,599 citations · Europe PMC · via Acenocoumarol

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.