KLKB1 Gene: Plasma Prekallikrein – Function, Mutations & Disease

The KLKB1 gene encodes plasma prekallikrein, a serine protease zymogen that circulates in the blood as a complex with high-molecular-weight kininogen. Upon activation by factor XIIa, plasma kallikrein cleaves kininogen to release bradykinin, a potent vasoactive peptide. KLKB1 plays a critical role in the intrinsic coagulation pathway, fibrinolysis, and the kallikrein-kinin system, contributing to inflammation and blood pressure regulation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa04610: Complement and coagulation cascades

• KEGG hsa04742: Taste transduction

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

• Reactome R-HSA-1474228: Bradykinin signaling

Plasma prekallikrein (UniProt P03952) is a 638-amino-acid glycoprotein synthesized primarily in the liver. It consists of four apple domains (A1–A4) and a serine protease domain. The zymogen is activated by factor XIIa via cleavage at Arg371-Ile372, yielding a heavy chain (A1–A4) and a light chain (catalytic domain). The active enzyme (plasma kallikrein) cleaves high-molecular-weight kininogen to release bradykinin, a key mediator of vasodilation and inflammation. KLKB1 also participates in the activation of factor XII, factor IX, and plasminogen, linking coagulation, fibrinolysis, and innate immunity.