This gene encodes coagulation factor XII which circulates
in blood as a zymogen. This single chain zymogen is converted to a
two-chain serine protease with an heavy chain (alpha-factor XIIa)
and a light chain. The heavy chain contains two fibronectin-type
domains, two epidermal growth factor (EGF)-like domains, a kringle
domain and a proline-rich domain, whereas the light chain contains
only a catalytic domain. On activation, further cleavages takes
place in the heavy chain, resulting in the production of
beta-factor XIIa light chain and the alpha-factor XIIa light chain
becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by
factor XII to form kallikrein, which then cleaves factor XII first
to alpha-factor XIIa and then to beta-factor XIIa. The active
factor XIIa participates in the initiation of blood coagulation,
fibrinolysis, and the generation of bradykinin and angiotensin. It
activates coagulation factors VII and XI. Defects in this gene do
not cause any clinical symptoms and the sole effect is that
whole-blood clotting time is prolonged.
