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Structural Modeling Insights into Human VKORC1 Phenotypes.

Authors: Czogalla, KJ  Watzka, M  Oldenburg, J 
Citation: Czogalla KJ, etal., Nutrients. 2015 Aug 14;7(8):6837-51. doi: 10.3390/nu7085313.
Pubmed: (View Article at PubMed) PMID:26287237
DOI: Full-text: DOI:10.3390/nu7085313

Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain gamma-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2.

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RGD Object Information
RGD ID: 11354881
Created: 2016-07-28
Species: All species
Last Modified: 2016-07-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.