VKORC1

Chr 16ARAD

vitamin K epoxide reductase complex subunit 1

NCBI Gene: 79001ENSG00000167397UniProt: Q9BQB6

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

Primary Disease Associations & Inheritance

Vitamin K-dependent clotting factors, combined deficiency of, 2MIM #607473
AR
Warfarin resistanceMIM #122700
AD
UniProtCoumarin resistance
75
ClinVar variants
19
Pathogenic / LP
0.16
pLI score
1
Active trials
Clinical Summary— VKORC1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 30 VUS of 75 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.02LOEUF
pLI 0.162
Z-score 1.55
OE 0.32 (0.13–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.31Z-score
OE missense 0.91 (0.76–1.09)
85 obs / 93.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.32 (0.13–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.76–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 2 / 6.2Missense obs/exp: 85 / 93.3Syn Z: 0.54

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic5
VUS30
Likely Benign6
Benign6
Conflicting1
14
Pathogenic
5
Likely Pathogenic
30
VUS
6
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
11
0
14
Likely Pathogenic
0
2
3
0
5
VUS
0
12
13
5
30
Likely Benign
0
2
3
1
6
Benign
0
3
2
1
6
Conflicting
—1
Total02232762

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Vitamin K-dependent clotting factors, combined deficiency of, 2

MIM #607473

Molecular basis of disorder known

Autosomal recessive

Warfarin resistance

MIM #122700

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Warfarin pharmacogenetics.
Johnson JA et al.·Trends Cardiovasc Med
2015Review
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.
Johnson JA et al.·Clin Pharmacol Ther
2017Guideline
[Cardiovascular pharmacogenomics].
Scibona P et al.·Arch Cardiol Mex
2014Review
Warfarin pharmacogenomics.
Cavallari LH et al.·Curr Opin Mol Ther
2009Review
Pharmacogenetics-based coumarin therapy.
Gage BF·Hematology Am Soc Hematol Educ Program
2006Review
Warfarin pharmacogenetics.
Limdi NA et al.·Pharmacotherapy
2008Review
Application of rapid genotyping of Warfarin individualized pharmacogenetic variants in Warfarin therapy.
Huang D et al.·Sci Rep
2024
Genomics of bleeding disorders.
Goodeve AC et al.·Haemophilia
2014Review
Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.
Piriyapongsa J et al.·Sci Rep
2024
Cardiovascular pharmacogenomics: expectations and practical benefits.
Turner RM et al.·Clin Pharmacol Ther
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Association Between VKORC1 Gene Polymorphisms and Osteopenia and Osteoporosis: A Systematic Review and Meta-Analysis.
Vesa ŞC et al.·Medicina (Kaunas)
2026🔓 Open AccessReview
Incidence of Vkorc1 gene mutations in brown rat (Rattus norvegicus) populations from downtown Madrid and their role in resistance to anticoagulant rodenticide: Implications for rodenticide management.
Bermejo-Nogales A et al.·Ecotoxicol Environ Saf
2026
Rapid population expansion drives the widespread spread of a dominant anticoagulant-resistance Vkorc1 allele in Asian house rats (Rattus tanezumi) across China.
Sun T et al.·Pest Manag Sci
2025
Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Gene Polymorphisms Predict Arterial Stiffness and Serum MGP Levels in Chronic Kidney Disease Patients.
Chen DH et al.·Genes (Basel)
2025🔓 Open AccessCohort
A new nuclear marker, the "VKORC1 gene exon 3 region", for the identification of Anatolian Rattus spp.
Çetintürk D et al.·BMC Zool
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Atrial Fibrillation

REGistry of Long-term AnTithrombotic TherApy-2

RECRUITING
NCT04347187National Medical Research Center for Cardiology, Ministry of Health of Russian FederationStarted 2015-01-15
Anticoagulants

External Resources

Links to major genomics databases and tools