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Gene: VKORC1

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The level of evidence to support the gene-disease relationship of VKORC1 and autosomal recessive combined deficiency of vitamin K-dependent clotting factors, type 2, is moderate. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

There is only one mutation known to result in the VKCFD2 phenotype. VKORC1:p.Arg98Trp causes diminished vitamin K epoxide reductase (VKOR) activity compared to that of the wild-type enzyme. VKORC1 function is not completely understood, but it localizes to the ER and its mislocalization due to the Arg98Trp variant is reported to be the mechanism of disease in VKCFD2 (PMID: 14765194, 24963046). At least 3 patients from 3 families in 5 publications have been reported with the same homozygous missense variant, Arg98Trp, which is considered a mutational hotspot (PMID: 12704386).

(ClinGen 2023)

VKORC1 is also associated with AD Warfarin resistance, MIM#122700, not included in screening.

Created: 6 Feb 2025, 5:16 a.m. | Last Modified: 6 Feb 2025, 5:16 a.m.

Panel Version: 1.1459

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM#607473

Publications

• 12704386
• 14765194
• 24963046
• 18315553