[VKORC1] 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. [provided by RefSeq].
RefSeq annotates 3 representative transcripts from 2 genes that we see as a complex (NM included in AceView variants .a, .i and .o), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 18 spliced variants
AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap, and it merges 2 different NCBI genes.
According to AceView, this gene is expressed at very high level
, 4.6 times the average gene in this release. The sequence
of this gene is defined by 548 GenBank accessions
from 464 cDNA clones, some from brain (seen 43 times), lung (32), pancreas (32), purified pancreatic islet (23), kidney (21), prostate (20), eye (19) and 158 other tissues
. We annotate structural defects or features
in 107 cDNA clones.
Alternative mRNA variants and regulation:
The gene contains 24 distinct introns
(23 gt-ag, 1 gc-ag). Transcription produces 19 different mRNAs
, 18 alternatively spliced variants and 1 unspliced form. There are 6 probable alternative promotors
, 2 non overlapping alternative last exons and 10 validated alternative polyadenylation sites
(see the diagram
). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 8 cassette exons
, overlapping exons with different boundaries, splicing versus retention of 10 introns. 495 bp of this gene are antisense to spliced gene ZNF646
, raising the possibility of regulated alternate expression.
Note that mRNA .cAug10 was found in vivo
, although it is a predicted target of nonsense mediated mRNA decay
There are 173 articles
specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases
(Cerebrovascular Disorders; Coagulation Protein Disorders; Coronary Disease; Coumarin resistance; Hemorrhage; Hemorrhagic Disorders; Lung Diseases; Thrombosis; Vitamin K-dependent clotting factors, combined deficiency of, 2; Warfarin resistance) and proposed to participate in processes
(oxidation reduction, positive regulation of coagulation, proteolysis, regulation of blood coagulation, response to antibiotic, response to organic cyclic substance, response to organic nitrogen, vitamin K metabolic process). Proteins are expected to have molecular functions
(oxidoreductase activity, peptidase activity, serine-type endopeptidase activity, vitamin-K-epoxide reductase (warfarin-insensitive) activity, vitamin-K-epoxide reductase (warfarin-sensitive) activity) and to localize
in various compartments (extracellular space, membrane, endoplasmic reticulum, endoplasmic reticulum membrane and 4 others
Protein coding potential:
15 spliced and the unspliced mRNAs putatively encode good proteins
, altogether 16 different isoforms (9 complete, 4 COOH complete, 3 partial
), some containing domains
Trypsin, Vitamin K epoxide reductase family [Pfam]; 1 of the 9 complete proteins appears to be secreted
. The remaining 3 mRNA variants (3 spliced) appear not to encode good proteins.
2 isoforms are annotated using as Met a Kozak-compatible
non-AUG start, thereby gaining a minimum of 154 amino acids N-terminal to the first AUG.
Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12
Map on chromosome 16, links to other databases and other names
This gene VKORC1andPRSS53 maps on chromosome 16, at 16p11.2 according to Entrez Gene. In AceView, it covers 12.93 kb
, from 31107264 to 31094335 (NCBI 37, August 2010), on the reverse strand.
manual annotations from OMIM_122700
, the SNP
view, gene overviews from Entrez Gene 339105
, expression data from ECgene
, UniGene Hs.324844
, molecular and other annotations from UCSC
, or our GOLD
The previous AceView annotation is here
The gene is also known as VKORC1andPRSS53, MSTP134, VKOR, MST134, MST576, VKCFD2, EDTP308, MGC2694, FLJ00289, IMAGE3455200, POL3S, UNQ308, VKORC1, PRSS53 or LOC339105, LOC79001. It has been described as vitamin K epoxide reductase complex subunit 1, phylloquinone epoxide reductase, vitamin K1 2,3-epoxide reductase subunit 1, vitamin K dependent clotting factors deficiency 2, vitamin K1 epoxide reductase (warfarin-sensitive), serine protease 53, EDTP308, polyserase 3, polyserase-3, polyserine protease 3.
This gene encodes proteins number: 184.108.40.206, 3.4.21.-.
Closest AceView homologs in other species
The closest mouse gene
, according to BlastP, is the AceView gene BC039632
The closest C.elegans gene
, according to BlastP, is the AceView/WormGene try-1
(e=6 10^-21), which may contain interesting functional annotation.
The closest A.thaliana gene
, according to BlastP, is the AceView gene AT4G21650andAT4G21630
(e=0.52), which may contain interesting functional annotation