F9 Gene: Coagulation Factor IX – Hemophilia B, Structure, and Variants

The F9 gene encodes coagulation factor IX, a vitamin K-dependent serine protease that circulates as an inactive zymogen. Upon activation by factor XIa or tissue factor/factor VIIa, factor IXa forms the tenase complex with factor VIIIa to activate factor X, a critical step in the intrinsic coagulation pathway. Mutations in F9 cause hemophilia B (Christmas disease), an X-linked recessive bleeding disorder. The gene spans approximately 34 kb on chromosome Xq27.1 and contains 8 exons.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa04610: Complement and coagulation cascades

• Reactome R-HSA-140837: Intrinsic pathway of fibrin clot formation

• Reactome R-HSA-140877: Formation of fibrin clot (clotting cascade)

Coagulation factor IX (UniProt P00740) is a 461-amino-acid glycoprotein synthesized in the liver as a preproprotein. After removal of the signal peptide and propeptide, the mature protein circulates as a zymogen. It contains an N-terminal Gla domain (γ-carboxyglutamic acid residues) for calcium-dependent membrane binding, two epidermal growth factor (EGF)-like domains, and a C-terminal trypsin-like serine protease domain. Activation by cleavage at Arg145-Ala146 and Arg180-Val181 yields the active factor IXa, which, in complex with factor VIIIa, converts factor X to Xa. The protein is vitamin K-dependent and undergoes post-translational γ-carboxylation.