VKORC1 vitamin K epoxide reductase complex subunit 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: VKORC1provided by HGNC
Official Full Name: vitamin K epoxide reductase complex subunit 1provided by HGNC
Primary source: HGNC:HGNC:23663
See related: Ensembl:ENSG00000167397 MIM:608547; AllianceGenome:HGNC:23663
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: VKOR; MST134; MST576; VKCFD2; EDTP308
Summary: 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]
Expression: Ubiquitous expression in liver (RPKM 74.3), fat (RPKM 26.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p11.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (31090854..31094797, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (31478282..31482234, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (31102175..31106118, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.
Title: New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.
Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.
Title: Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.
Frequency of polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes related to the metabolism of Warfarin in healthy donors from Cali, Colombia.
Title: Frequency of polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes related to the metabolism of Warfarin in healthy donors from Cali, Colombia.
FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
Title: FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state.
Title: Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state.
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.
Title: The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.
Association of VKORC1 polymorphisms and major bleedings in patients who are treated with vitamin K antagonists.
Title: Association of VKORC1 polymorphisms and major bleedings in patients who are treated with vitamin K antagonists.
Frequency Distribution of CYP2C9 and VKORC1 Mutations among Bulgarian Patients and their Importance for Anticoagulant Therapy.
Title: Frequency Distribution of CYP2C9 and VKORC1 Mutations among Bulgarian Patients and their Importance for Anticoagulant Therapy.
Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.
Title: Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.
VKORC1 gene polymorphism (-1639G>A) in warfarin therapy patients of Pakistani population.
Title: VKORC1 gene polymorphism (-1639G>A) in warfarin therapy patients of Pakistani population.

Submit: New GeneRIF Correction See all GeneRIFs (337)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Vitamin K-dependent clotting factors, combined deficiency of, type 2 MedGen: C1843832 OMIM: 607473 GeneReviews: Not available	Compare labs
Warfarin response MedGen: C0750384 OMIM: 122700 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D16S419 (e-PCR), detects polymorphism
- UniSTS:21834

D16S3131 (e-PCR), detects polymorphism
- UniSTS:35933

D1S1425 (e-PCR)
- UniSTS:149621

G35510 (e-PCR)
- UniSTS:44150

RH64898 (e-PCR)
- UniSTS:90748

RH69900 (e-PCR)
- UniSTS:91088

GDB:631813 (e-PCR)
- UniSTS:158430

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables quinone binding	IEA Inferred from Electronic Annotation more info
enables vitamin-K-epoxide reductase (warfarin-insensitive) activity	IDA Inferred from Direct Assay more info	PubMed
enables vitamin-K-epoxide reductase (warfarin-sensitive) activity	IBA Inferred from Biological aspect of Ancestor more info
enables vitamin-K-epoxide reductase (warfarin-sensitive) activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bone development	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-glutamic acid carboxylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-glutamic acid carboxylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of coagulation	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in response to organonitrogen compound	IEA Inferred from Electronic Annotation more info
involved_in vitamin K metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in vitamin K metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in xenobiotic metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
is_active_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: vitamin K epoxide reductase complex subunit 1

Names: phylloquinone epoxide reductase; vitamin K dependent clotting factors deficiency 2; vitamin K1 2,3-epoxide reductase subunit 1; vitamin K1 epoxide reductase (warfarin-sensitive)

NP_001298240.1

EC 1.17.4.4

NP_076869.1

EC 1.17.4.4

NP_996560.1

EC 1.17.4.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011564.1 RefSeqGene

Range

5159..9102

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_582

mRNA and Protein(s)

NM_001311311.2 → NP_001298240.1 vitamin K epoxide reductase complex subunit 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).

Source sequence(s)

AK312005, BM663008, CN484751

UniProtKB/Swiss-Prot

Q9BQB6

Related

ENSP00000326135.7, ENST00000319788.11

Conserved Domains (1) summary

cd12917
Location:10 → 177

VKOR_euk; Vitamin K epoxide reductase family in eukaryotes, excluding plants
NM_024006.6 → NP_076869.1 vitamin K epoxide reductase complex subunit 1 isoform 1

See identical proteins and their annotated locations for NP_076869.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) lacks an alternate in-frame exon compared to variant 3. It encodes isoform 1, which is shorter than isoform 3.

Source sequence(s)

AY358456, AY423044, BC002911, BI822140

Consensus CDS

CCDS10703.1

UniProtKB/Swiss-Prot

A6NIQ6, B2R4Z6, Q6UX90, Q7Z2R4, Q9BQB6

UniProtKB/TrEMBL

A0A0S2Z6I4

Related

ENSP00000378426.2, ENST00000394975.3

Conserved Domains (1) summary

cd12917
Location:10 → 149

VKOR_euk; Vitamin K epoxide reductase family in eukaryotes, excluding plants
NM_206824.3 → NP_996560.1 vitamin K epoxide reductase complex subunit 1 isoform 2

See identical proteins and their annotated locations for NP_996560.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two alternate internal exons, resulting in a frame-shift compared to variant 3. It encodes isoform 2, which is shorter than and has a distinct C-terminus compared to isoform 3.

Source sequence(s)

AK129513, BI822140, BM663008

Consensus CDS

CCDS10704.1

UniProtKB/TrEMBL

A0A0S2Z5X7

Related

ENSP00000346969.4, ENST00000354895.4

Conserved Domains (1) summary

cl01729
Location:10 → 58

VKOR; Vitamin K epoxide reductase (VKOR) family