Factor V Leiden (FVL) results from a single point mutation in the F5 gene (guanine to adenine at nucleotide 1691), which leads to a single amino acid change (replacement of the normal arginine [Arg] with glutamine [Gln] at amino acid 506).
(Panel A) Normal factor V physiology. Activated protein C (aPC) cleaves factor Va at the Arg506 cleavage site, resulting in inactivation. The cleavage at Arg506 exposes additional cleavage sites at Arg306 and Arg679.
(Panel B) FVL. In heterozygous carriers of FVL, Arg506 is replaced by Gln, making factor Va resistant to the initial cleavage by aPC. This is the basis for aPC resistance.
Refer to UpToDate for a more detailed discussion of the mechanism and physiology, including cleavage of unactivated factor V by aPC.