F12 Gene – Coagulation Factor XII (Hageman Factor) | Function, Mutations & Disease

The F12 gene encodes coagulation factor XII (FXII, Hageman factor), a serine protease zymogen that initiates the intrinsic pathway of coagulation and the contact activation system. FXII is activated upon contact with negatively charged surfaces, leading to activation of factor XI and prekallikrein, and triggering bradykinin production. The gene is located on chromosome 5q35.3 and spans approximately 12 kb. Mutations in F12 are associated with hereditary angioedema type III (HAE3) and FXII deficiency (Hageman trait).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Intrinsic pathway of coagulation (Reactome: R-HSA-140837)

• Contact activation system (Reactome: R-HSA-166658)

• Kallikrein-kinin system (Reactome: R-HSA-166662)

Coagulation factor XII (FXII) is a 596-amino-acid glycoprotein synthesized primarily in the liver and secreted into plasma as a zymogen. It contains an N-terminal fibronectin type II domain, two EGF-like domains, a kringle domain, a proline-rich region, and a C-terminal trypsin-like serine protease domain. Upon contact with anionic surfaces (e.g., glass, kaolin, polyphosphates), FXII undergoes autoactivation to FXIIa, which then activates factor XI and prekallikrein. FXIIa also cleaves high-molecular-weight kininogen to release bradykinin, a potent vasodilator. The protein is essential for the contact activation pathway but not for hemostasis in vivo; deficiency does not cause bleeding.