F12 Gene

The F12 gene (F12 stands for coagulation factor XII) is a protein-coding gene located on chromosome 5q35.3.

The F12 gene encodes coagulation factor XII (Hageman factor), which circulates in the blood as a zymogen. This single-chain zymogen is converted into a two-chain serine protease with a heavy chain (alpha factor XIIa) and a light chain. The heavy chain contains two fibronectin-like domains, two epidermal growth factor (EGF)-like domains, a kringle domain, and a proline-rich domain, whereas the light chain contains only one catalytic domain.

Upon activation, further cleavage occurs in the heavy chain leading to the formation of beta factor XIIa light chain, and 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.

Active factor XIIa is involved in the initiation of blood clotting, fibrinolysis, and the formation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause clinical symptoms, and the only effect is to prolong blood clotting time.

Diseases associated with F12 include:

• Factor XII deficiency

and

• Angioedema hereditary mutation in F12 (Hereditary Angioedema Type III).

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