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

    Gene ID: 79001, updated on 3-Nov-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
    mouse all
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    Genomic context

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    See VKORC1 in Genome Data Viewer
    Location:
    16p11.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (31090854..31094797, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (31478282..31482234, complement)
    RS_2024_09 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 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. VKORC1 genetic polymorphism and risk of venous thromboembolism in postmenopausal women: new findings and meta-analysis. Verstuyft C, et al. J Thromb Haemost, 2009 Jun. PMID 19320825
    2. VKORC1 polymorphisms in Amerindian populations of Brazil. Perini JA, et al. Pharmacogenomics, 2008 Nov. PMID 19018718
    3. The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype. Nimptsch K, et al. Br J Nutr, 2009 Jun. PMID 19025725
    4. VKORC1 variant genotypes influence warfarin response in patients undergoing total joint arthroplasty: a pilot study. González Della Valle A, et al. Clin Orthop Relat Res, 2009 Jul. PMID 19034590, Free PMC Article
    5. The Arg98Trp mutation in human VKORC1 causing VKCFD2 disrupts a di-arginine-based ER retention motif. Czogalla KJ, et al. Blood, 2014 Aug 21. PMID 24963046

    See all (458) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Is a Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism a Risk Factor for Nephrolithiasis in Sarcoidosis?
      Title: Is a Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism a Risk Factor for Nephrolithiasis in Sarcoidosis?
    2. 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.
    3. 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.
    4. 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.
    5. FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
      Title: FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (338)

    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
    		not available
    Warfarin response
    MedGen: C0750384 OMIM: 122700 GeneReviews: Not available
    		not available

    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 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 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_2024_08

    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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