Fibroblast growth factor 12 (FGF12)

Fibroblast growth factor 12 (FGF12) is an intracellular member of the fibroblast growth factor family, classified as a fibroblast growth factor homologous factor (FHF), also called FHF1. Unlike most FGFs, FGF12 does not have a classical secretion signal and acts predominantly inside excitable cells like neurons and cardiomyocytes. Its most studied role is the regulation of voltage-gated sodium channels—especially Nav1.5 in the heart—affecting channel availability and cardiac action potential, with mutations linked to arrhythmogenic phenotypes such as Brugada syndrome. In neurons, pathogenic mutations in FGF12 disrupt sodium channel inactivation and are associated with severe epileptic encephalopathies, such as EIEE47. FGF12 is also expressed in auditory neurons, essential for hearing and balance. Although not traditionally considered a receptor, FGF12 has recently been shown to be secreted and internalized, influencing apoptosis and cytoskeletal regulation, and is under investigation as a genetic or therapeutic target in some cardiac and neurological diseases[1][3][5][7][11].

Other names

FGF-12FHF1EIEE47FGF12B

Modulation of sodium channel gating (not drug-mediated, but FGF12 itself regulates Nav1.5 and neuronal Na+ channels)[3][5] Apoptosis inhibition (by cell-internalized FGF12 protein)[3]