Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1)

Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) is an endoplasmic reticulum membrane-bound enzyme in the vitamin K cycle, catalyzing the reduction of vitamin K 2,3-epoxide to vitamin K, thereby supporting γ-carboxylation of vitamin K-dependent proteins required for coagulation and cellular antioxidation[1][2][3]. VKORC1L1 is structurally and mechanistically distinct from its paralog VKORC1 and shows much lower sensitivity to inhibition by classic vitamin K antagonists such as warfarin[1][3]. VKORC1L1 is upregulated under oxidative stress and contributes to antioxidant protection, particularly in extrahepatic tissues such as vasculature, testis, lung, and osteoblasts[1][3]. Genetic variants have been linked to inter-individual differences in warfarin dose requirement. While VKORC1L1 deficiency or downregulation is associated with enhanced oxidative stress, inflammation, and vascular smooth muscle proliferation—potentially contributing to cardiovascular disease—VKORC1L1 is not a major direct target for anticoagulant therapy due to its low inhibitor sensitivity[1][3].

Other names

Vitamin K epoxide reductase complex subunit 1-like protein 1VKORC1-like protein 1VKORC1L1 protein

Inhibition of VKORC1L1 by vitamin K antagonists blocks the reduction of vitamin K epoxide to its active form, impairing the carboxylation of vitamin K-dependent clotting factors and antioxidant proteins[1][3]. Polymorphisms in VKORC1L1 can affect individual responses to warfarin[1].