F2 Gene: Coagulation Factor II (Thrombin) – Function, Mutations & Disease

The F2 gene encodes prothrombin (coagulation factor II), a vitamin K-dependent glycoprotein that is proteolytically converted to thrombin in the coagulation cascade. Thrombin converts fibrinogen to fibrin, activates platelets, and regulates coagulation factors V, VIII, XI, and XIII. Mutations in F2 can cause thrombophilia (gain-of-function) or hypoprothrombinemia/dysprothrombinemia (loss-of-function).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG: hsa04610 – Complement and coagulation cascades

• Reactome: R-HSA-140877 – Formation of Fibrin Clot (Clotting Cascade)

• Reactome: R-HSA-76002 – Platelet activation

• signaling and aggregation

• Reactome: R-HSA-109582 – Hemostasis

Prothrombin (UniProt P00734) is a 622-amino-acid vitamin K-dependent glycoprotein synthesized in the liver. It circulates as a zymogen and is activated to thrombin by factor Xa in the presence of factor Va, calcium, and phospholipids. Thrombin is a serine protease that cleaves fibrinogen to fibrin, activates platelets, and amplifies coagulation via feedback activation of factors V, VIII, XI, and XIII. The protein contains a Gla domain (calcium binding), two kringle domains, and a trypsin-like serine protease domain. Post-translational gamma-carboxylation of glutamic acid residues is essential for function.