General Information, Educational Resources
The genetic variation or polymorphism (G1691A or R506Q) is from a single nucleotide substitution at position 1691 where a guanine (G) is substituted for an adenine (A). This type of nucleotide substitution results in a missense mutation. This single change in the nucleotide sequence (or missense mutation) causes a change in the amino acid placed at position 506 on the protein molecule; the amino acid changes from an arginine (R; Arg) to a glutamine (Q; Gln), thus the reason the polymorphism is identified as R506Q. This single change in an amino acid can alter the activity and binding characteristics of factor V because at normal pH (7.35-7.45), Gln is not charged however Arg is positively charged. In fact, this is one of the sites where activated protein C cleaves factor V to inactivate it, but now it can’t because of this change. Thus, the mutated protein structure of factor V is now less responsive to the inhibitory action of activated protein C. This allows factor V to continue to be available for use in the propagation and formation of a clot.