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Defective cleavage of FV variant at a.a.534

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9930449

PubChem

R-HSA-9930449

Description

Factor V Leiden (the most common) and Factor V Bonn thrombophilias are inherited conditions caused by the missense variants FV R534Q and FV A540V, respectively. These genetic mutations lead to resistance to activated protein C (APC), impairing its ability to inactivate factor Va (FVa) by cleaving it at residue R534 (Bertina RM et al., 1994; van Stralen KJ et al., 2008; Pezeshkpoor B et al., 2016). The defective cleavage of these FV variants may also interfere with APC-mediated inactivation of factor VIIIa (FVIIIa), where non-activated but APC-cleaved FV functions as an APC cofactor (Váradi K et al., 1996; Pezeshkpoor B et al., 2016). In addition to APC resistance, FVa Bonn (A540V) exhibits increased affinity for factor Xa (FXa) (Pezeshkpoor B et al., 2016), which diminishes APC-mediated cleavage at R534, as FXa and APC share a common exosite on FV (reviewed by Bernardi F, 2016). These conditions result in prolonged FVa activity, enhanced function of the prothrombinase FVa:FXa complex, and sustained thrombin generation, which may increase the risk of developing deep venous thrombosis in individuals carrying the FV Leiden or FV Bonn mutation (reviewed by Pastori et al., 1999; Perez-Pujol S et al., 2012; van Cott EM et al., 2016; Albagoush SA et al., 2023; Moore GW et al., 2023).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 3** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P04070	Vitamin K-dependent protein C	PROC	view
P07225	Vitamin K-dependent protein S	PROS PROS1	view
P12259	Coagulation factor V	F5	view

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