GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00001175
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Rattus norvegicus
Trait State in Taxon B
Rattus norvegicus -Denmark; UK; Germany
Ancestral State
Data not curated
Taxonomic Status
Taxon A
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
Show more ... omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
Show more ... omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
Yes
Taxon B Description
Rattus norvegicus -Denmark; UK; Germany
GENOTYPIC CHANGE
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Y139C
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Rost S; Fregin A; Ivaskevicius V; Conzelmann E; Hörtnagel K; Pelz HJ; Lappegard K; Seifried E; et al. ... show more
Abstract
Coumarin derivatives such as warfarin represent the therapy of choice for the long-term treatment and prevention of thromboembolic events. Coumarins target blood coagulation by inhibiting the vitamin K epoxide reductase multiprotein complex (VKOR). This complex recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a cofactor that is essential for the post-translational gamma-carboxylation of several blood coagulation factors. Despite extensive efforts, the components of the VKOR complex have not been identified. The complex has been proposed to be involved in two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2; Online Mendelian Inheritance in Man (OMIM) 607473), and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR; OMIM 122700). Here we identify, by using linkage information from three species, the gene vitamin K epoxide reductase complex subunit 1 (VKORC1), which encodes a small transmembrane protein of the endoplasmic reticulum. VKORC1 contains missense mutations in both human disorders and in a warfarin-resistant rat strain. Overexpression of wild-type VKORC1, but not VKORC1 carrying the VKCFD2 mutation, leads to a marked increase in VKOR activity, which is sensitive to warfarin inhibition.
Additional References
RELATED GEPHE
Related Haplotypes
7
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