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

Gene ID: 79001, updated on 5-Mar-2024

Summary

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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
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Genomic context

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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_000016.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:31074971-31075598 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:31075599-31076226 Neighboring gene zinc finger protein 668 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:31084437-31085237 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:31085443-31085976 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:31085977-31086509 Neighboring gene zinc finger protein 646 Neighboring gene serine protease 53 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:31099941-31100441 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:31104343-31105051 Neighboring gene zinc finger protein ENSP00000375192-like Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10745 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10746 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10747 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10748 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:31117007-31117823 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:31119431-31120324 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:31120325-31121217 Neighboring gene branched chain keto acid dehydrogenase kinase Neighboring gene ReSE screen-validated silencer GRCh37_chr16:31128803-31129029

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state. Li S, et al. Blood Adv, 2023 May 23. PMID 36508285, Free PMC Article
  2. Association of VKORC1 polymorphisms and major bleedings in patients who are treated with vitamin K antagonists. van Heteren DM, et al. J Intern Med, 2023 Jan. PMID 36125842, Free PMC Article
  3. VKORC1 gene polymorphism (-1639G>A) in warfarin therapy patients of Pakistani population. Ghafoor MB, et al. J Pak Med Assoc, 2022 Mar. PMID 35320217
  4. Variation in VKORC1 Is Associated with Vascular Dementia. Mur J, et al. J Alzheimers Dis, 2021. PMID 33682710, Free PMC Article
  5. Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity. Janssen R, et al. Med Hypotheses, 2020 Nov. PMID 33254525, Free PMC Article

See all (451) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
    Title: FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose.
EBI GWAS Catalog
Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC2694, FLJ00289, IMAGE3455200

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
NP_076869.1
NP_996560.1

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

  1. NG_011564.1 RefSeqGene

    Range
    5159..9102
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_582

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    31090854..31094797 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    31478282..31482234 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BQB6.1 GenPept UniProtKB/Swiss-Prot:Q9BQB6

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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