Under normal physiological conditions, activated protein C (APC) regulates clotting by cleaving factor Va (FVa) at residues R534 and R334, thereby preventing excessive clot formation. This Reactome event describes two missense variants, FV R334T (FV Cambridge) and FV I387T (FV Liverpool), which interfere with APC-mediated cleavage at R334. This disrupted FVa proteolysis leads to prolonged clotting activity of FVa, potentially increasing the risk of venous thromboembolism (VTE) in individuals carrying either of these mutations (Williamson D et al., 1998; Franco RF et al., 1998; Norström E et al., 2002; Mumford AD et al., 2003; Steen M et al., 2004; reviewed by Moore GW et al., 2023).
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