VKORC1

Protein identityUniProt · HPA

UniProt accession

Q9BQB6

Gene

VKORC1

Ensembl

ENSG00000167397

Chromosome

16

Canonical length

163 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Endoplasmic reticulum

OverviewNCBI Gene

This gene encodes the catalytic subunit of the vitamin K epoxide reductase complex, which is responsible for the reduction of inactive vitamin K 2,3-epoxide to active vitamin K in the endoplasmic reticulum membrane. Vitamin K is a required co-factor for carboxylation of glutamic acid residues by vitamin K-dependent gamma-carboxylase in blood-clotting enzymes. Allelic variation in this gene is associated with vitamin k-dependent clotting factors combined deficiency of 2, and increased resistance or sensitivity to warfarin, an inhibitor of vitamin K epoxide reductase. Pseudogenes of this gene are located on chromosomes 1 and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

163 residues, UniProt reviewed canonical sequence.

>Q9BQB6|VKORC1
     1  MGSTWGSPGW VRLALCLTGL VLSLYALHVK AARARDRDYR ALCDVGTAIS CSRVFSSRWG
    61  RGFGLVEHVL GQDSILNQSN SIFGCIFYTL QLLLGCLRTR WASVLMLLSS LVSLAGSVYL
   121  AWILFFVLYD FCIVCITTYA INVSLMWLSF RKVQEPQGKA KRH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VKORC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

526 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VKORC1.

Disease | AllUniProt

Conditions VKORC1 is implicated in, by any mechanism.

• Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) MIM:607473
• Coumarin resistance (CMRES) MIM:122700

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 54 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Warfarin response
• Vitamin K-dependent clotting factors, combined deficiency of, type 2
• Hereditary combined deficiency of vitamin K-dependent clotting factors

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.02

gnomAD pLI

0.16

gnomAD missense Z

0.31

DepMap mean gene effect

-0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• bone development
• peptidyl-glutamic acid carboxylation
• positive regulation of coagulation
• vitamin K metabolic process
• xenobiotic metabolic process

Molecular functions

• quinone binding
• vitamin-K-epoxide reductase (warfarin-sensitive) activity
• vitamin-K-epoxide reductase (warfarin-insensitive) activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum lumen
• endoplasmic reticulum membrane

Protein domainsUniProt · Pfam · InterPro

• Vitamin K epoxide reductase
• VKOR domain superfamily
• Vitamin K epoxide reductase complex subunit 1
• Vitamin K epoxide reductase family

KeywordsUniProt

• Disulfide bond
• Endoplasmic reticulum
• Membrane
• Oxidoreductase
• Quinone
• Redox-active center
• Transmembrane
• Transmembrane helix