Structure

         FVIII is synthesized as a single polypeptide chain, later cleaved to form a hetero dimer protein. This dimer has two polypeptide subunits, the factor VIII light chain and factor VIII heavy chain.  The polypeptide has six evolutionarily conserved domains; three A (A1, A2, and A3), one B (B), and two C (C1 and C2).  It is homologous to coagulation factor V.

Function

Genetics

         FVIII is encoded by the F8 gene, located on Xq28 (28th position on the q arm of the X chromosome).  Mutations in this gene are associated with hemophilia A, a X-linked recessive disorder.  There are 1,300 mutations associated with Hemophilia A in the F8 gene, ranging from single base substitutions to multi base indels.  These mutations typically lower the concentration of or inactivate the FVIII protein.  As it can no longer participate in the coagulation processes, blood clotting does not occur properly, leading to the excessive bleeding commonly seen in hemophilia.  The severity of hemophilia depends largely on the mutation, with loss-of-function mutations resulting in more severe hemophilia than those lowing FVIII'c concentration.