242:
219:
1032:
physiological process of vitamin K recycling. The availability of reduced vitamin K is of importance for activation vitamin K 2,3-epoxide. The reduction of vitamin K epoxide is then responsible for the carboxylation of glutamic acid residues in some blood-clotting proteins, including factor VII, factor IX, and factor X. VKORC1 is of therapeutic interest both for its role in contributing to high interpatient variability in coumarin anticoagulant dose requirements and as a potential player in vitamin K deficiency disorders.
116:
141:
493:
1152:, the common ("wild-type") G allele is replaced by the A allele. People with an A allele (or the "A haplotype") produce less VKORC1 than do those with the G allele (or the "non-A haplotype"). The prevalence of these variants also varies by race, with 90–95% of Asians, 37% of Caucasians and 14% of Africans carrying the A allele. The end result is a decreased amount of clotting factors and therefore, a decreased ability to clot.
248:
147:
1066:
1036:
activities and leads to a reduced amount of vitamin K available to serve as a cofactor for clotting proteins. Inappropriate dosing of warfarin has been associated with a substantial risk of both major and minor hemorrhage. As the pharmacological target of warfarin, VKORC1 is considered a candidate gene for the variability in warfarin response. Previous researches have shown that the
1158:
is an anticoagulant that opposes the procoagulant effect of vitamin K by inhibiting the VKORC enzyme. If these patients are prescribed warfarin for another medical purpose, they will require lower doses than usual because the patient is already deficient in VKORC. They may experience severe bleeding
1035:
Warfarin is a commonly prescribed oral anticoagulant, or blood thinner used to treat blood clots such as deep vein thrombosis and pulmonary embolism and to prevent stroke in people who have atrial fibrillation, valvular heart disease or artificial heart valves. Warfarin causes inhibition on VKORC1
1170:
Two alternatively spliced transcripts encoding different isoforms have also been described. These isoforms result in warfarin resistance (requiring higher doses) in humans and rats, because the amount and effectiveness of the VKORC enzyme has not changed, but the ability of warfarin to exert its
1031:
cycle. VKORC1 is a 163 amino acid integral membrane protein associated with the endoplasmic reticulum and VKORC1 mRNA is broadly expressed in many different tissues. VKORC1 is involved in the vitamin K cycle by reduction of vitamin K epoxide to vitamin K, which is the rate-limiting step in the
1788:
Yang J, Chen Y, Li X, Wei X, Chen X, Zhang L, Zhang Y, Xu Q, Wang H, Li Y, Lu C, Chen W, Zeng C, Yin T (October 2013). "Influence of CYP2C9 and VKORC1 genotypes on the risk of hemorrhagic complications in warfarin-treated patients: a systematic review and meta-analysis".
1341:
Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Müller CR, Strom TM, Oldenburg J (February 2004). "Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2".
1641:
Zhang J, Tian L, Zhang Y, Shen J (November 2015). "The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis".
255:
154:
1598:"Effect of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin maintenance dose in children aged less than 18 years: a protocol for systematic review and meta-analysis"
1137:
gene encodes a subunit of the enzyme that is responsible for reducing vitamin K 2,3-epoxide to the activated form, a reduction reaction. A genetic polymorphism on the
1914:
Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB (October 2011).
1555:"Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin dosage in Han-Chinese patients: A systematic review and meta-analysis"
721:
702:
77:
1524:
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".
1967:
1247:
1229:
1481:"A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity"
1126:
In humans, mutations in this gene are associated with deficiencies in vitamin-K-dependent clotting factors. Fatal bleeding (internal) and
1011:. This enzymatic protein complex is responsible for reducing vitamin K 2,3-epoxide to its active form, which is important for effective
241:
944:
937:
1314:
1159:
and bruising. Lower warfarin doses are needed to inhibit VKORC1 and to produce an anticoagulant effect in carriers of the A allele.
1113:
218:
1268:
1171:
effect (antagonize the enzyme) has changed. These isoform mutations are rare except in
Ethiopian and certain Jewish populations.
1216:
1195:
1282:
Ryan P., Owen; Li, Gong; Hersh, Sagreiya; Teri E., Klein; Russ B., Altmana (October 2010). "VKORC1 Pharmacogenomics
Summary".
1149:
1091:
140:
115:
1212:
1191:
57:
254:
153:
1076:
1916:"Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing"
1479:
Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, Wu JY, Chen YT (July 2005).
247:
146:
1095:
1080:
1019:). In humans, mutations in this gene can be associated with deficiencies in vitamin-K-dependent clotting factors.
766:
65:
1715:
Shaw K, Amstutz U, Kim RB, Lesko LJ, Turgeon J, Michaud V, Hwang S, Ito S, Ross C, Carleton BC (August 2015).
1818:
Fung E, Patsopoulos NA, Belknap SM, O'Rourke DJ, Robb JF, Anderson JL, Shworak NW, Moore JH (November 2012).
1759:
Gaikwad T, Ghosh K, Shetty S (September 2014). "VKORC1 and CYP2C9 genotype distribution in Asian countries".
1087:
747:
1717:"Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy"
129:
1863:"Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis"
1874:
1351:
44:
48:, EDTP308, IMAGE3455200, MST134, MST576, VKCFD2, VKOR, vitamin K epoxide reductase complex subunit 1
891:
836:
1411:
Wadelius M, Sörlin K, Wallerman O, Karlsson J, Yue QY, Magnusson PK, Wadelius C, Melhus H (2004).
1747:
1375:
89:
920:
899:
895:
865:
844:
840:
492:
1945:
1902:
1849:
1806:
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1739:
1716:
1703:
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1629:
1584:
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1502:
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1434:
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1310:
37:
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1882:
1839:
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1609:
1574:
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1533:
1492:
1424:
1359:
1302:
334:
265:
209:
164:
85:
1820:"Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin"
1160:
309:
1878:
1355:
1141:
gene results in a patient having less available VKORC enzyme to complete this reaction.
1940:
1915:
1897:
1862:
1844:
1819:
1698:
1671:
1624:
1597:
1579:
1554:
1393:
1306:
636:
631:
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621:
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534:
1961:
521:
1751:
1772:
1654:
1452:
Yamamura, M.; Yamamoto, M. (1989). "Tumor metastasis and the fibrinolytic system".
1379:
327:
106:
69:
1887:
1802:
1735:
93:
1570:
1413:"Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors"
1252:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1234:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1065:
1049:
1016:
410:
1614:
1127:
1012:
226:
123:
73:
1040:
genotype of patients also played a role in warfarin metabolism and response.
1028:
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470:
348:
293:
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192:
179:
81:
1949:
1906:
1853:
1835:
1810:
1780:
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1707:
1662:
1633:
1588:
1545:
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1506:
1438:
1429:
1412:
1371:
1324:
1931:
1465:
984:
979:
1861:
Jorgensen AL, FitzGerald RJ, Oyee J, Pirmohamed M, Williamson PR (2012).
1497:
1480:
1155:
968:
811:
792:
1363:
778:
733:
1688:
1037:
1004:
952:
688:
1269:"Entrez Gene: VKORC1 vitamin K epoxide reductase complex, subunit 1"
651:
647:
1297:
Garcia AA, Reitsma PH (2008). "VKORC1 and the vitamin K cycle".
997:
501:
61:
1167:
recommends lower starting doses of warfarin in these patients.
1164:
1059:
1672:"Structural Modeling Insights into Human VKORC1 Phenotypes"
1052:
have been identified on chromosome 1 and the X chromosome.
550:
vitamin-K-epoxide reductase (warfarin-insensitive) activity
1301:. Vitamins & Hormones. Vol. 78. pp. 23–33.
540:
vitamin-K-epoxide reductase (warfarin-sensitive) activity
1596:
Takeuchi M, Kobayashi T, Brandão LR, Ito S (June 2016).
317:
1009:
Vitamin K epOxide
Reductase Complex (VKORC) subunit 1
482:
1163:
can reveal the presence of the genetic mutation and
1130:can result from a decreased ability to form clots.
913:
884:
858:
829:
1670:Czogalla KJ, Watzka M, Oldenburg J (August 2015).
1208:
1206:
1204:
1187:
1185:
1183:
264:
163:
1048:The human gene is located on chromosome 16. Two
16:Protein-coding gene in the species Homo sapiens
1213:GRCm38: Ensembl release 89: ENSMUSG00000096145
8:
1336:
1334:
1192:GRCh38: Ensembl release 89: ENSG00000167397
1094:. Unsourced material may be challenged and
1553:Zhang J, Chen Z, Chen C (September 2016).
1027:The VKORC1 protein is a key enzyme in the
662:
517:
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101:
1939:
1896:
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1843:
1697:
1687:
1623:
1613:
1578:
1496:
1428:
1114:Learn how and when to remove this message
1263:
1261:
586:intracellular membrane-bounded organelle
1179:
1920:Clinical Pharmacology and Therapeutics
18:
1824:Seminars in Thrombosis and Hemostasis
269:
230:
225:
168:
127:
122:
7:
1092:adding citations to reliable sources
602:peptidyl-glutamic acid carboxylation
1791:International Journal of Cardiology
627:response to organic cyclic compound
622:response to organonitrogen compound
1526:Antioxidants & Redox Signaling
910:
881:
855:
826:
802:
783:
757:
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693:
487:
405:
343:
322:
14:
1064:
491:
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145:
139:
114:
632:regulation of blood coagulation
1773:10.1016/j.thromres.2014.05.028
1655:10.1016/j.thromres.2015.09.018
1150:single-nucleotide polymorphism
571:endoplasmic reticulum membrane
566:integral component of membrane
502:More reference expression data
471:More reference expression data
1:
1307:10.1016/S0083-6729(07)00002-7
238:
137:
1968:Genes on human chromosome 16
1888:10.1371/journal.pone.0044064
1803:10.1016/j.ijcard.2013.07.151
1736:10.1097/FTD.0000000000000192
1417:The Pharmacogenomics Journal
1724:Therapeutic Drug Monitoring
1571:10.1016/j.mgene.2016.07.002
617:vitamin K metabolic process
359:stromal cell of endometrium
1984:
1615:10.1186/s13643-016-0280-y
1248:"Mouse PubMed Reference:"
1230:"Human PubMed Reference:"
983:
978:
974:
967:
951:
945:Chr 7: 127.49 – 127.49 Mb
932:
917:
888:
877:
862:
833:
822:
809:
805:
790:
786:
777:
764:
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687:
672:
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520:
516:
499:
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468:
417:
408:
375:Descending thoracic aorta
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316:
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304:
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274:
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207:
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186:
173:
136:
113:
104:
100:
55:
52:
42:
35:
30:
26:
21:
1485:Human Molecular Genetics
938:Chr 16: 31.09 – 31.1 Mb
535:oxidoreductase activity
1836:10.1055/s-0032-1328891
1538:10.1089/ars.2006.8.347
1430:10.1038/sj.tpj.6500220
1284:Pharmacogenet Genomics
637:response to antibiotic
1932:10.1038/clpt.2011.185
1460:(4 Pt 2–1): 1246–54.
1144:Specifically, in the
581:endoplasmic reticulum
379:right coronary artery
130:Chromosome 16 (human)
1088:improve this section
457:white adipose tissue
387:left coronary artery
271:7 F3|7 69.81 cM
232:Chromosome 7 (mouse)
1879:2012PLoSO...744064J
1761:Thrombosis Research
1643:Thrombosis Research
1454:Gan to Kagaku Ryoho
1364:10.1038/nature02214
1356:2004Natur.427..537R
1133:The product of the
433:islet of Langerhans
363:right lobe of liver
1602:Systematic Reviews
1498:10.1093/hmg/ddi180
1056:Clinical relevance
767:ENSMUSG00000096145
595:Biological process
559:Cellular component
528:Molecular function
94:VKORC1 - orthologs
1689:10.3390/nu7085313
1491:(13): 1745–1751.
1394:"Warfarin Sodium"
1350:(6974): 537–541.
1124:
1123:
1116:
994:
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990:
989:
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962:
928:
927:
907:
906:
873:
872:
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818:
817:
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773:
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754:
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728:
727:
709:
708:
657:
656:
607:blood coagulation
512:
511:
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507:
477:
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464:
463:
402:
401:
300:
299:
199:
198:
1975:
1953:
1943:
1910:
1900:
1890:
1857:
1847:
1814:
1797:(4): 4234–4243.
1784:
1755:
1721:
1711:
1701:
1691:
1682:(8): 6837–6851.
1666:
1637:
1627:
1617:
1592:
1582:
1549:
1532:(3–4): 347–353.
1511:
1510:
1500:
1476:
1470:
1469:
1449:
1443:
1442:
1432:
1408:
1402:
1401:
1390:
1384:
1383:
1338:
1329:
1328:
1294:
1288:
1287:
1279:
1273:
1272:
1265:
1256:
1255:
1244:
1238:
1237:
1226:
1220:
1210:
1199:
1189:
1119:
1112:
1108:
1105:
1099:
1068:
1060:
1003:encodes for the
976:
975:
947:
940:
923:
911:
902:
882:
878:RefSeq (protein)
868:
856:
847:
827:
803:
784:
758:
739:
713:
694:
663:
612:bone development
518:
504:
495:
488:
473:
425:secondary oocyte
413:
411:Top expressed in
406:
383:body of pancreas
351:
349:Top expressed in
344:
323:
306:
296:
283:
272:
257:
250:
244:
233:
221:
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171:
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118:
102:
96:
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40:
19:
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1913:
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1517:Further reading
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1161:Genetic testing
1148:1639 (or 3673)
1120:
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1085:
1069:
1058:
1046:
1025:
985:View/Edit Mouse
980:View/Edit Human
943:
936:
933:Location (UCSC)
919:
898:
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843:
839:
835:
748:ENSG00000167397
641:
590:
554:
545:quinone binding
500:
469:
460:
455:
453:proximal tubule
451:
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441:urinary bladder
439:
435:
431:
427:
423:
409:
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395:pituitary gland
393:
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371:ascending aorta
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208:Gene location (
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105:Gene location (
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36:
17:
12:
11:
5:
1981:
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1954:
1926:(4): 625–629.
1911:
1858:
1830:(8): 893–904.
1815:
1785:
1767:(3): 537–544.
1756:
1730:(4): 428–436.
1712:
1667:
1649:(5): 955–961.
1638:
1593:
1550:
1520:
1518:
1515:
1513:
1512:
1471:
1444:
1403:
1385:
1330:
1315:
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421:primary oocyte
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397:
396:
392:
388:
384:
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376:
372:
368:
367:thoracic aorta
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313:
310:RNA expression
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98:
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54:
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49:
41:
33:
32:
28:
27:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1980:
1969:
1966:
1965:
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1951:
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1937:
1933:
1929:
1925:
1921:
1917:
1912:
1908:
1904:
1899:
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1889:
1884:
1880:
1876:
1873:(8): e44064.
1872:
1868:
1864:
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1829:
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1073:This section
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842:
838:
832:
828:
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823:RefSeq (mRNA)
821:
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795:
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782:
780:
776:
769:
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557:
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526:
523:
522:Gene ontology
519:
515:
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498:
494:
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472:
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456:
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444:
440:
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20:
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1601:
1562:
1558:
1529:
1525:
1488:
1484:
1474:
1457:
1453:
1447:
1423:(1): 40–48.
1420:
1416:
1406:
1397:
1388:
1347:
1343:
1298:
1292:
1283:
1277:
1251:
1242:
1233:
1224:
1169:
1154:
1145:
1143:
1138:
1134:
1132:
1125:
1110:
1104:October 2016
1101:
1086:Please help
1074:
1047:
1034:
1026:
1008:
1000:
995:
918:
892:NP_001298240
889:
863:
837:NM_001311311
834:
810:
791:
765:
746:
720:
701:
681:
676:
449:right kidney
333:
326:
292:127,494,789
279:127,492,235
53:External IDs
1565:: 197–209.
1050:pseudogenes
1017:coagulation
391:right ovary
191:31,095,980
178:31,090,842
31:Identifiers
1608:(1): 105.
1286:: 642–644.
1219:, May 2017
1198:, May 2017
1175:References
1128:hemorrhage
996:The human
337:(ortholog)
74:HomoloGene
1676:Nutrients
1559:Meta Gene
1398:Drugs.com
1299:Vitamin K
1075:does not
1029:vitamin K
921:NP_848715
900:NP_996560
896:NP_076869
866:NM_178600
845:NM_206824
841:NM_024006
667:Orthologs
82:GeneCards
1962:Category
1950:21900891
1907:22952875
1867:PLOS ONE
1854:23041981
1811:23932037
1781:24908449
1752:20381277
1744:26186657
1708:26287237
1663:26433837
1634:27334984
1589:27617219
1546:16677080
1507:15888487
1439:14676821
1372:14765194
1325:18374188
1215:–
1194:–
1156:Warfarin
1023:Function
1013:clotting
969:Wikidata
646:Sources:
576:membrane
437:yolk sac
1941:3187550
1898:3430615
1875:Bibcode
1845:4134937
1699:4555152
1625:4917995
1580:5006145
1466:2730023
1380:4424197
1352:Bibcode
1217:Ensembl
1196:Ensembl
1096:removed
1081:sources
779:UniProt
734:Ensembl
673:Species
652:QuickGO
312:pattern
170:16p11.2
38:Aliases
1948:
1938:
1905:
1895:
1852:
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1809:
1779:
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1587:
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1544:
1505:
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1437:
1378:
1370:
1344:Nature
1323:
1313:
1146:VKORC1
1139:VKORC1
1135:VKORC1
1038:CYP2C9
1005:enzyme
1001:VKORC1
955:search
953:PubMed
812:Q9CRC0
793:Q9BQB6
689:Entrez
483:BioGPS
429:zygote
86:VKORC1
70:106442
62:608547
45:VKORC1
22:VKORC1
1748:S2CID
1720:(PDF)
1376:S2CID
722:27973
703:79001
682:Mouse
677:Human
648:Amigo
445:liver
335:Mouse
328:Human
275:Start
210:Mouse
174:Start
107:Human
78:11416
1946:PMID
1903:PMID
1850:PMID
1807:PMID
1777:PMID
1740:PMID
1704:PMID
1659:PMID
1630:PMID
1585:PMID
1542:PMID
1503:PMID
1462:PMID
1435:PMID
1368:PMID
1321:PMID
1311:ISBN
1079:any
1077:cite
1044:Gene
998:gene
318:Bgee
266:Band
227:Chr.
165:Band
124:Chr.
58:OMIM
1936:PMC
1928:doi
1893:PMC
1883:doi
1840:PMC
1832:doi
1799:doi
1795:168
1769:doi
1765:134
1732:doi
1694:PMC
1684:doi
1651:doi
1647:136
1620:PMC
1610:doi
1575:PMC
1567:doi
1534:doi
1493:doi
1425:doi
1360:doi
1348:427
1303:doi
1165:FDA
1090:by
1007:,
288:End
187:End
90:OMA
66:MGI
1964::
1944:.
1934:.
1924:90
1922:.
1918:.
1901:.
1891:.
1881:.
1869:.
1865:.
1848:.
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1828:38
1826:.
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1489:14
1487:.
1483:.
1458:16
1456:.
1433:.
1419:.
1415:.
1396:.
1374:.
1366:.
1358:.
1346:.
1333:^
1319:.
1309:.
1260:^
1250:.
1232:.
1203:^
1182:^
650:/
294:bp
281:bp
193:bp
180:bp
88:;
84::
80:;
76::
72:;
68::
64:;
60::
1952:.
1930::
1909:.
1885::
1877::
1871:7
1856:.
1834::
1813:.
1801::
1783:.
1771::
1754:.
1734::
1710:.
1686::
1680:7
1665:.
1653::
1636:.
1612::
1606:5
1591:.
1569::
1563:9
1548:.
1536::
1530:8
1509:.
1495::
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1421:4
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1362::
1354::
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1271:.
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1117:)
1111:(
1106:)
1102:(
1098:.
1084:.
1015:(
212:)
109:)
92::
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