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FLASH GENE

Symbol

VKORC1

contributors: mct - updated : 07-04-2014

HGNC name	vitamin K epoxide reductase complex, subunit 1
HGNC id	23663

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	VKCFD2 vitamin K-dependent clotting factors, combined deficiency 2
Location	16p11.2      Physical location : 31.102.175 - 31.106.276
Synonym name	vitamin K dependent clotting factors deficiency 2
Synonym symbol(s)	VKOR, MST134, MST576, UNQ308, VKCFD2, MGC2694, FLJ00289
EC.number	1.1.4.1

DNA

TYPE	functioning gene
STRUCTURE	4.10 kb     3 Exon(s)

regulatory sequence	Promoter
text structure	promoter polymorphism (-1639 G>A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients, and associated with inter-individual and inter-ethnic differences

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_024006 3 - 1042 NP_076869 18 163 - 2005 15947090 NM_206824 2 - 907 NP_996560 - 92 - 2005 15947090 has a distinct C-terminus

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       predominantly Rattus norvegicus Nervous brain       lowly Rattus norvegicus Reproductive male system testis     lowly Rattus norvegicus Respiratory lung       highly Rattus norvegicus Urinary kidney       moderately Rattus norvegicus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	pancreas, liver, heart, kidney, lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a C-terminal endoplasmic membrane retention signal (Lys-Lys-X-X or Lys-X-Lys-X-X )
	a transmembrane domain

HOMOLOGY

interspecies	ortholog to murine Vkorc1
	ortholog to rattus vkorc1

intraspecies

paralog to VKORC1L1

Homologene

FAMILY

VKOR family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic

basic FUNCTION	acting as a target of warfarin
	essential role of VKORC1 in vitamin K-dependent gamma-glutamyl carboxylation
	may play a role in osteoporosis
	both VKORC1 and SERP1, might have a synergistic function in eliminating reactive oxygen species generated during the vitamin K 2,3-epoxide reductase (VKOR) redox process
	relevant molecule for cardiovascular diseases, since it is the target of oral anticoagulant drugs and plays a role in soft tissue calcification
	main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK)
	in liver, quasi-exclusive participation of VKORC1 in the VKOR activity
	exclusive involvement of VKORC1 in the liver
	VKORC1L1 and VKORC1 might potentially have different physiological functions

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

vitamin

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	VKORC1 interacting with SERP1, and both might have a synergistic function in eliminating reactive oxygen species generated during the VKOR redox process
	MIR133A1 appears to have a direct regulatory effect on expression of VKORC1, and this regulation may have potential importance for anticoagulant therapy or aortic calcification

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

VKCFD2

Susceptibility

to warfarin sensitivity to systemic lupus erythematosus (SLE) to coronary artery disease in the presence of coronary calcification

Variant & Polymorphism other	promoter polymorphism (-1639 G>A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients
	genetic variants in VKORC1, which are involved in vitamin K reduction and associated with DVT, correlate with SLE development
	rs2359612C allele is associated with increased risk of coronary artery disease in the presence of coronary calcification

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	homozygous Vkorc1-deficient mice developed normally until birth, but within 2-20 days after birth, the knockout mice died due to extensive, predominantly intracerebral haemorrhage
	homozygous Vkorc1-/- mice die in 2–20 days after birth by extensive bleeding due to a total deficiency of the gamma-carboxylation of the clotting factors in liver