Kininogen-1 (KNG1)

Kininogen-1 is a multidomain plasma glycoprotein encoded by the KNG1 gene in humans. Through alternative splicing, KNG1 encodes both high-molecular-weight kininogen (HMWK) and low-molecular-weight kininogen (LMWK). HMWK acts as a crucial cofactor in the intrinsic (contact) pathway of blood coagulation, serving as a carrier for prekallikrein and coagulation factor XI, and is necessary for the generation of the nonapeptide bradykinin when cleaved by kallikrein. Bradykinin, released from kininogen-1, is a potent mediator of vasodilation, vascular permeability, pain, and inflammation. While LMWK is not involved in coagulation, both forms act as protease inhibitors of the cystatin type and can modulate inflammation and vascular responses. Loss or dysfunction of kininogen-1 is linked to rare hereditary coagulopathies as well as diseases involving heightened inflammation or vascular permeability

Other names

High-molecular-weight kininogenLow-molecular-weight kininogenAlpha-2-thiol proteinase inhibitorWilliams-Fitzgerald-Flaujeac factorHMWK-kallikrein factorFitzgerald factorHMWK (for high-molecular-weight kininogen)LMWK (for low-molecular-weight kininogen)

Inhibition of kallikrein prevents cleavage of kininogen-1 to bradykinin (reducing inflammation, swelling) Bradykinin receptor antagonism blocks downstream effects (vasodilation, pain, edema) Replacement therapy in deficiency states restores pathway control