VKORC1

Vitamin K epoxide reductase complex, subunit 1
Identifiers
Symbols	VKORC1; EDTP308; FLJ00289; IMAGE3455200; MGC2694; MST134; MST576; VKCFD2; VKOR
External IDs	OMIM: 608547 MGI: 106442 HomoloGene: 11416 GeneCards: VKORC1 Gene
EC number	1.1.4.1
Gene Ontology Molecular function • oxidoreductase activity • vitamin-K-epoxide reductase (warfarin-sensitive) activity Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • membrane • integral to membrane Biological process • peptidyl-glutamic acid carboxylation • post-translational protein modification • cellular protein metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	79001	27973
Ensembl	ENSG00000167397	ENSMUSG00000030804
UniProt	Q9BQB6	Q9CRC0
RefSeq (mRNA)	NM_024006.4	NM_178600.2
RefSeq (protein)	NP_076869.1	NP_848715.1
Location (UCSC)	Chr 16: 31.09 – 31.11 Mb	Chr 7: 135.03 – 135.04 Mb
PubMed search	[1]	[2]

Vitamin K epoxide reductase complex subunit 1 is an enzyme that in humans is encoded by the VKORC1 gene.

Vitamin K is essential for blood clotting but must be enzymatically activated. This enzymatically activated form of vitamin K is a reduced form required for the carboxylation of glutamic acid residues in some blood-clotting proteins. The product of this gene encodes the enzyme that is responsible for reducing vitamin K 2,3-epoxide to the enzymatically activated form. Fatal bleeding can be caused by vitamin K deficiency and by the vitamin K antagonist warfarin, and it is the product of this gene that is sensitive to warfarin. In humans, mutations in this gene can be associated with deficiencies in vitamin-K-dependent clotting factors. In humans and rats it has also been associated with warfarin resistance - but these mutations are rare except in Ethiopian and certain Jewish populations. Two pseudogenes have been identified on chromosome 1 and the X chromosome. Two alternatively spliced transcripts encoding different isoforms have been described.

Further reading

• Oldenburg J, Bevans CG, Müller CR, Watzka M (2006). "Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.". Antioxid. Redox Signal. 8 (3-4): 347–53. doi:10.1089/ars.2006.8.347. PMID 16677080. 
• Oldenburg J, Bevans CG, Fregin A, et al. (2007). "Current pharmacogenetic developments in oral anticoagulation therapy: the influence of variant VKORC1 and CYP2C9 alleles.". Thromb. Haemost. 98 (3): 570–8. PMID 17849045. 
• Oldenburg J, von Brederlow B, Fregin A, et al. (2001). "Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex.". Thromb. Haemost. 84 (6): 937–41. PMID 11154138. 
• Fregin A, Rost S, Wolz W, et al. (2002). "Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K-dependent clotting factors to the centromeric region of chromosome 16.". Blood 100 (9): 3229–32. doi:10.1182/blood-2002-03-0698. PMID 12384421. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=403697. 
• Rost S, Fregin A, Ivaskevicius V, et al. (2004). "Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.". Nature 427 (6974): 537–41. doi:10.1038/nature02214. PMID 14765194. 
• Li T, Chang CY, Jin DY, et al. (2004). "Identification of the gene for vitamin K epoxide reductase.". Nature 427 (6974): 541–4. doi:10.1038/nature02254. PMID 14765195. 
• Goodstadt L, Ponting CP (2004). "Vitamin K epoxide reductase: homology, active site and catalytic mechanism.". Trends Biochem. Sci. 29 (6): 289–92. doi:10.1016/j.tibs.2004.04.004. PMID 15276181. 
• D'Andrea G, D'Ambrosio RL, Di Perna P, et al. (2005). "A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin.". Blood 105 (2): 645–9. doi:10.1182/blood-2004-06-2111. PMID 15358623. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Harrington DJ, Underwood S, Morse C, et al. (2005). "Pharmacodynamic resistance to warfarin associated with a Val66Met substitution in vitamin K epoxide reductase complex subunit 1.". Thromb. Haemost. 93 (1): 23–6. doi:10.1267/THRO05010023. PMID 15630486. 
• Tie JK, Nicchitta C, von Heijne G, Stafford DW (2005). "Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation.". J. Biol. Chem. 280 (16): 16410–6. doi:10.1074/jbc.M500765200. PMID 15716279. 
• Bodin L, Verstuyft C, Tregouet DA, et al. (2005). "Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity.". Blood 106 (1): 135–40. doi:10.1182/blood-2005-01-0341. PMID 15790782. 
• Wadelius M, Chen LY, Downes K, et al. (2005). "Common VKORC1 and GGCX polymorphisms associated with warfarin dose.". Pharmacogenomics J. 5 (4): 262–70. doi:10.1038/sj.tpj.6500313. PMID 15883587. 
• Rieder MJ, Reiner AP, Gage BF, et al. (2005). "Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose.". N. Engl. J. Med. 352 (22): 2285–93. doi:10.1056/NEJMoa044503. PMID 15930419. 
• Sconce EA, Khan TI, Wynne HA, et al. (2005). "The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen.". Blood 106 (7): 2329–33. doi:10.1182/blood-2005-03-1108. PMID 15947090. 
• Wang Y, Zhen Y, Shi Y, et al. (2005). "Vitamin k epoxide reductase: a protein involved in angiogenesis.". Mol. Cancer Res. 3 (6): 317–23. doi:10.1158/1541-7786.MCR-04-0221. PMID 15972850. 
• Bodin L, Horellou MH, Flaujac C, et al. (2005). "A vitamin K epoxide reductase complex subunit-1 (VKORC1) mutation in a patient with vitamin K antagonist resistance.". J. Thromb. Haemost. 3 (7): 1533–5. doi:10.1111/j.1538-7836.2005.01449.x. PMID 15978113. 
• Wajih N, Hutson SM, Owen J, Wallin R (2005). "Increased production of functional recombinant human clotting factor IX by baby hamster kidney cells engineered to overexpress VKORC1, the vitamin K 2,3-epoxide-reducing enzyme of the vitamin K cycle.". J. Biol. Chem. 280 (36): 31603–7. doi:10.1074/jbc.M505373200. PMID 16030016.