FGF14 Gene - Fibroblast Growth Factor 14: Function, Mutations, and Associated Diseases

FGF14 (Fibroblast Growth Factor 14) is a member of the fibroblast growth factor (FGF) family, but unlike canonical FGFs, it functions primarily as an intracellular protein (iFGF) that modulates voltage-gated sodium channels (Nav) and other ion channels in neurons. It is highly expressed in the central nervous system, particularly in the cerebellum, and is critical for neuronal excitability, synaptic transmission, and motor coordination. Mutations in FGF14 cause spinocerebellar ataxia 27 (SCA27), a neurodegenerative disorder characterized by progressive ataxia, tremor, and cognitive impairment.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACT:13685 – Voltage gated sodium channel complex

• WP:WP2848 – Spinocerebellar ataxia pathways

• WP:WP3932 – Fibroblast growth factor signaling

FGF14 (also known as FHF4) is a 247-amino acid intracellular fibroblast growth factor homologous factor (iFHF) that lacks a classical signal peptide and does not act as a secreted growth factor. Instead, it binds directly to the C-terminal tail of voltage-gated sodium channels (Nav1.1, Nav1.2, Nav1.6) and modulates their gating properties, including inactivation kinetics and resurgent current. FGF14 is essential for normal cerebellar Purkinje cell firing and motor coordination. Loss of FGF14 function leads to impaired sodium channel activity, reduced neuronal excitability, and progressive ataxia.