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Aliases for VKORC1 Gene

Aliases for VKORC1 Gene

  • Vitamin K Epoxide Reductase Complex Subunit 1 2 3 5
  • Vitamin K Dependent Clotting Factors Deficiency 2 2 3
  • Vitamin K1 2,3-Epoxide Reductase Subunit 1 3 4
  • VKOR 3 4
  • Vitamin K1 Epoxide Reductase (Warfarin-Sensitive) 3
  • Vitamin K Epoxide Reductase Complex, Subunit 1 3
  • Phylloquinone Epoxide Reductase 3
  • EC 1.17.4.4 4
  • EC 1.1.4.1 63
  • EDTP308 3
  • MST134 3
  • MST576 3
  • VKCFD2 3

External Ids for VKORC1 Gene

Previous HGNC Symbols for VKORC1 Gene

  • VKCFD2

Previous GeneCards Identifiers for VKORC1 Gene

  • GC16M031138
  • GC16M031009
  • GC16M028663

Summaries for VKORC1 Gene

Entrez Gene Summary for VKORC1 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]

GeneCards Summary for VKORC1 Gene

VKORC1 (Vitamin K Epoxide Reductase Complex Subunit 1) is a Protein Coding gene. Diseases associated with VKORC1 include Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, 2 and Coumarin Resistance. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Ubiquinol biosynthesis. GO annotations related to this gene include quinone binding and vitamin-K-epoxide reductase (warfarin-sensitive) activity. An important paralog of this gene is ENSG00000255439.

UniProtKB/Swiss-Prot for VKORC1 Gene

  • 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.

Gene Wiki entry for VKORC1 Gene

PharmGKB "VIP" Summary for VKORC1 Gene

No data available for Tocris Summary , fRNAdb sequence ontologies and piRNA Summary for VKORC1 Gene

Genomics for VKORC1 Gene

Regulatory Elements for VKORC1 Gene

Enhancers for VKORC1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around VKORC1 on UCSC Golden Path with GeneCards custom track

Genomic Location for VKORC1 Gene

Chromosome:
16
Start:
31,090,842 bp from pter
End:
31,096,337 bp from pter
Size:
5,496 bases
Orientation:
Minus strand

Genomic View for VKORC1 Gene

Genes around VKORC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
VKORC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for VKORC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VKORC1 Gene

Proteins for VKORC1 Gene

  • Protein details for VKORC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BQB6-VKOR1_HUMAN
    Recommended name:
    Vitamin K epoxide reductase complex subunit 1
    Protein Accession:
    Q9BQB6
    Secondary Accessions:
    • A6NIQ6
    • B2R4Z6
    • Q6UX90
    • Q7Z2R4

    Protein attributes for VKORC1 Gene

    Size:
    163 amino acids
    Molecular mass:
    18235 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • The location of two cysteine active-site residues within a proposed transmembrane is consistent both with the known hydrophobic environment of the thiol redox site of the enzyme and with the lipophilicity of vitamin K and warfarin (coumadin).
    SequenceCaution:
    • Sequence=AAQ88821.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for VKORC1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VKORC1 Gene

Proteomics data for VKORC1 Gene at MOPED

Selected DME Specific Peptides for VKORC1 Gene

Post-translational modifications for VKORC1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

Domains & Families for VKORC1 Gene

Protein Domains for VKORC1 Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q9BQB6

UniProtKB/Swiss-Prot:

VKOR1_HUMAN :
  • The number of transmembrane domains and the membrane topology are controversial; supporting evidence is available both for models with three transmembrane domains (PubMed:15716279 and PubMed:22923610) and four transmembrane domains (PubMed:20696932 and PubMed:20978134). According to PubMed:15716279 and PubMed:22923610 the N-terminus of the protein is in the endoplasmic reticulum lumen, while the C-terminus is in the cytosol, which is in favor of three transmembrane domains. According to PubMed:20696932, both N-terminus and C-terminus are in the cytosol, indicating the presence of four transmembrane domains. Besides, the 3D-structure of a bacterial ortholog shows four transmembrane domains. Moreover, proteins that reside in the endoplasmic reticulum lumen can catalyze the reduction of the active site cysteines, possibly via Cys-43 and Cys-51 (PubMed:20696932 and PubMed:20978134), but less efficiently than the synthetic compound dithiothreitol (in vitro). Location of Cys-43 and Cys-51 in the endoplasmic reticulum lumen would be in agreement with four transmembrane domains. Again, these data are controversial, and papers do not agree on the effects of mutating Cys-43 and Cys-51, probably because of differences in the assay systems.
  • Belongs to the VKOR family.
Domain:
  • The number of transmembrane domains and the membrane topology are controversial; supporting evidence is available both for models with three transmembrane domains (PubMed:15716279 and PubMed:22923610) and four transmembrane domains (PubMed:20696932 and PubMed:20978134). According to PubMed:15716279 and PubMed:22923610 the N-terminus of the protein is in the endoplasmic reticulum lumen, while the C-terminus is in the cytosol, which is in favor of three transmembrane domains. According to PubMed:20696932, both N-terminus and C-terminus are in the cytosol, indicating the presence of four transmembrane domains. Besides, the 3D-structure of a bacterial ortholog shows four transmembrane domains. Moreover, proteins that reside in the endoplasmic reticulum lumen can catalyze the reduction of the active site cysteines, possibly via Cys-43 and Cys-51 (PubMed:20696932 and PubMed:20978134), but less efficiently than the synthetic compound dithiothreitol (in vitro). Location of Cys-43 and Cys-51 in the endoplasmic reticulum lumen would be in agreement with four transmembrane domains. Again, these data are controversial, and papers do not agree on the effects of mutating Cys-43 and Cys-51, probably because of differences in the assay systems.
Family:
  • Belongs to the VKOR family.
genes like me logo Genes that share domains with VKORC1: view

No data available for Gene Families for VKORC1 Gene

Function for VKORC1 Gene

Molecular function for VKORC1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Phylloquinone + oxidized dithiothreitol + H(2)O = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + 1,4-dithiothreitol.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by warfarin (coumadin).
UniProtKB/Swiss-Prot Function:
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.

Enzyme Numbers (IUBMB) for VKORC1 Gene

genes like me logo Genes that share phenotypes with VKORC1: view

Human Phenotype Ontology for VKORC1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for VKORC1 Gene

MGI Knock Outs for VKORC1:

Animal Model Products

No data available for Gene Ontology (GO) - Molecular Function , Transcription Factor Targets and HOMER Transcription for VKORC1 Gene

Localization for VKORC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for VKORC1 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for VKORC1 Gene COMPARTMENTS Subcellular localization image for VKORC1 gene
Compartment Confidence
endoplasmic reticulum 5
chloroplast 2
extracellular 2
plasma membrane 2

No data available for Gene Ontology (GO) - Cellular Components for VKORC1 Gene

Pathways & Interactions for VKORC1 Gene

genes like me logo Genes that share pathways with VKORC1: view

Pathways by source for VKORC1 Gene

Interacting Proteins for VKORC1 Gene

Gene Ontology (GO) - Biological Process for VKORC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007596 blood coagulation IMP 16270630
GO:0017187 peptidyl-glutamic acid carboxylation IMP,TAS 20978134
GO:0042373 vitamin K metabolic process IDA,TAS --
GO:0043687 post-translational protein modification TAS --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with VKORC1: view

No data available for SIGNOR curated interactions for VKORC1 Gene

Drugs & Compounds for VKORC1 Gene

(75) Drugs for VKORC1 Gene - From: DrugBank, PharmGKB, ClinicalTrials, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Warfarin Approved Pharma inhibitor, Target 435
Acenocoumarol Approved Pharma inhibitor, Target 27
Phenprocoumon Approved Pharma inhibitor, Target 28
Menadione Approved Nutra inhibitor, Target, cofactor 207
Dicumarol Approved Pharma inhibitor, Target 0

(18) Additional Compounds for VKORC1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
vitamin k1
  • 2',3'-trans-Vitamin K1
  • 2-Methyl-3-phythyl-1,4-naphthochinon
  • 2-Methyl-3-phytyl-1,4-naphthochinon
  • 2-Methyl-3-phytyl-1,4-naphthoquinone
  • 2-Methyl-3-phytyl-1,4-napthoquinone
12001-79-5
2,3-Butanediol
  • 2,3-Butandiol
  • 2,3-Butanediol
  • 2,3-Butanodiol
  • 2,3-Butylene glycol
  • 2,3-Dihydroxybutane
513-85-9
2,3-Epoxymenaquinone
Glucosylceramide (d18:1/16:0)
  • 1-O-b-D-Glucopyranosyl-Ceramide
  • 1-O-beta-delta-Glucopyranosyl-Ceramide
  • Ganglioside GL1a
  • Gaucher cerebroside
  • Glc-beta1->1'Cer
85305-87-9
Oxidized dithiothreitol
genes like me logo Genes that share compounds with VKORC1: view

Transcripts for VKORC1 Gene

Unigene Clusters for VKORC1 Gene

Vitamin K epoxide reductase complex, subunit 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for VKORC1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b · 4c · 4d
SP1: - -
SP2: - - -
SP3: - -
SP4: - - - -
SP5: -

Relevant External Links for VKORC1 Gene

GeneLoc Exon Structure for
VKORC1
ECgene alternative splicing isoforms for
VKORC1

Expression for VKORC1 Gene

mRNA expression in normal human tissues for VKORC1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for VKORC1 Gene

This gene is overexpressed in Liver (x4.3).

Protein differential expression in normal tissues from HIPED for VKORC1 Gene

This gene is overexpressed in Pancreas (10.5) and Islet of Langerhans (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for VKORC1 Gene



SOURCE GeneReport for Unigene cluster for VKORC1 Gene Hs.324844

mRNA Expression by UniProt/SwissProt for VKORC1 Gene

Q9BQB6-VKOR1_HUMAN
Tissue specificity: Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.
genes like me logo Genes that share expression patterns with VKORC1: view

Protein tissue co-expression partners for VKORC1 Gene

Primer Products

Orthologs for VKORC1 Gene

This gene was present in the common ancestor of animals.

Orthologs for VKORC1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia VKORC1 35
  • 87.73 (n)
  • 90.18 (a)
VKORC1 36
  • 90 (a)
OneToMany
dog
(Canis familiaris)
Mammalia VKORC1 35
  • 87.93 (n)
  • 90.8 (a)
VKORC1 36
  • 91 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Vkorc1 35
  • 83.02 (n)
  • 85.71 (a)
Vkorc1 16
Gm21974 36
  • 85 (a)
ManyToMany
Vkorc1 36
  • 85 (a)
ManyToMany
chimpanzee
(Pan troglodytes)
Mammalia VKORC1 35
  • 99.59 (n)
  • 100 (a)
VKORC1 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Vkorc1 35
  • 83.96 (n)
  • 84.37 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 52 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 52 (a)
OneToMany
African clawed frog
(Xenopus laevis)
Amphibia LOC398467 35
zebrafish
(Danio rerio)
Actinopterygii vkorc1 35
  • 56.04 (n)
  • 53.75 (a)
vkorc1 36
  • 50 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Vkor 35
  • 47.49 (n)
  • 39.04 (a)
Vkor 36
  • 37 (a)
OneToMany
Species with no ortholog for VKORC1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for VKORC1 Gene

ENSEMBL:
Gene Tree for VKORC1 (if available)
TreeFam:
Gene Tree for VKORC1 (if available)

Paralogs for VKORC1 Gene

Paralogs for VKORC1 Gene

(1) SIMAP similar genes for VKORC1 Gene using alignment to 9 proteins:

Pseudogenes.org Pseudogenes for VKORC1 Gene

genes like me logo Genes that share paralogs with VKORC1: view

Variants for VKORC1 Gene

Sequence variations from dbSNP and Humsavar for VKORC1 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type
rs104894539 Coumarin resistance (CMRES) 31,094,645(-) TGCAC(G/T)TGAAG nc-transcript-variant, reference, missense
rs104894540 Coumarin resistance (CMRES) 31,094,596(-) CGACG(C/T)GGGCA nc-transcript-variant, reference, missense
rs104894541 Coumarin resistance (CMRES) 31,094,558(-) CCTCC(A/G)GGTGT nc-transcript-variant, reference, missense
VAR_021824 Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2)
VAR_021825 Coumarin resistance (CMRES)

Structural Variations from Database of Genomic Variants (DGV) for VKORC1 Gene

Variant ID Type Subtype PubMed ID
nsv905729 CNV Loss 21882294
dgv2670n71 CNV Loss 21882294
nsv457483 CNV Loss 19166990
nsv833193 CNV Gain+Loss 17160897
dgv2672n71 CNV Loss 21882294
esv999616 CNV Gain 20482838

Variation tolerance for VKORC1 Gene

Residual Variation Intolerance Score: 88.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.21; 4.80% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for VKORC1 Gene

Human Gene Mutation Database (HGMD)
VKORC1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VKORC1 Gene

Disorders for VKORC1 Gene

MalaCards: The human disease database

(9) MalaCards diseases for VKORC1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
vitamin k-dependent clotting factors, combined deficiency of, 2
  • combined deficiency of vitamin k-dependent clotting factors 2
coumarin resistance
  • warfarin sensitivity
hereditary combined deficiency of vitamin k-dependent clotting factors
  • hereditary combined deficiency of factors ii, vii, ix and x
vkorc1-related altered drug metabolism
  • coumarin resistance
vitamin k antagonists toxicity or dose selection
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

VKOR1_HUMAN
  • Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM:607473]: VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. {ECO:0000269 PubMed:14765194}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Coumarin resistance (CMRES) [MIM:122700]: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. {ECO:0000269 PubMed:14765194, ECO:0000269 PubMed:20946155}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for VKORC1

Genetic Association Database (GAD)
VKORC1
Human Genome Epidemiology (HuGE) Navigator
VKORC1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
VKORC1
genes like me logo Genes that share disorders with VKORC1: view

No data available for Genatlas for VKORC1 Gene

Publications for VKORC1 Gene

  1. Pharmacodynamic resistance to warfarin is associated with nucleotide substitutions in VKORC1. (PMID: 18680536) Harrington D.J. … Mumford A.D. (J. Thromb. Haemost. 2008) 3 23 48 67
  2. The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. (PMID: 16611310) Montes R. … Hermida J. (Br. J. Haematol. 2006) 3 23 25 26
  3. Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. (PMID: 16677080) Oldenburg J. … Watzka M. (Antioxid. Redox Signal. 2006) 3 23 25 26
  4. Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. (PMID: 15790782) Bodin L. … Loriot M.A. (Blood 2005) 3 23 25 26
  5. A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. (PMID: 16201835) Reitsma P.H. … BA1ller H.R. (PLoS Med. 2005) 3 23 25 26

Products for VKORC1 Gene

Sources for VKORC1 Gene

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