VKORC1

Vitamin K epoxide reductase complex, subunit 1, also known as VKORC1, is a human gene.cite web | title = Entrez Gene: VKORC1 vitamin K epoxide reductase complex, subunit 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79001| accessdate = ]

PBB_Summary
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summary_text = 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 and, in humans and rats, with warfarin resistance. Two pseudogenes have been identified on chromosome 1 and the X chromosome. Two alternatively spliced transcripts encoding different isoforms have been described.cite web | title = Entrez Gene: VKORC1 vitamin K epoxide reductase complex, subunit 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79001| accessdate = ]

References

Further reading

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

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