FGF12: Fibroblast Growth Factor 12
A key regulator of neuronal excitability and cardiac function
Gene Information Card
| Symbol | FGF12 |
|---|---|
| Full Name | Fibroblast Growth Factor 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q28-q29 |
| NCBI Gene ID | 2257 ncbi.nlm.nih.gov/gene/2257 |
| Ensembl ID | ENSG00000183778 |
| UniProt ID | P61328 |
| OMIM ID | 601513 |
| HGNC ID | 3670 |
| Aliases | FHF1, FGF12B, FHF-1 |
Description
FGF12 (fibroblast growth factor 12) is a member of the fibroblast growth factor homologous factor (FHF) subfamily. Unlike canonical FGFs, FGF12 lacks a signal peptide and is not secreted; it functions intracellularly as a voltage-gated sodium channel (Nav) interacting protein. FGF12 modulates neuronal and cardiac excitability by binding to the C-terminal tail of Nav channels, influencing channel gating and trafficking. Mutations in FGF12 are associated with early infantile epileptic encephalopathy (EIEE) and cardiac arrhythmias.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early infantile epileptic encephalopathy 47 (EIEE47) | Loss-of-function mutations impair Nav channel modulation, leading to neuronal hyperexcitability and seizures. | ClinVar, OMIM |
| Cardiac arrhythmia (e.g., Brugada syndrome-like phenotype) | Altered Nav1.5 channel gating due to FGF12 mutations disrupts cardiac action potential propagation. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal muscle | 6.1 | Low |
| Testis | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous expression |
| H9c2 (cardiomyoblast) | 7.8 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.334C>T (p.Arg112*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.431G>A (p.Arg144Gln) | Missense | Rare | Impaired Nav binding; associated with EIEE47 |
| c.509T>C (p.Leu170Pro) | Missense | Rare | Altered channel modulation; cardiac phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce FGF12 protein levels or disrupt Nav channel binding, leading to neuronal hyperexcitability and epilepsy.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported in FGF12.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg144Gln) may act dominant-negative by competing with wild-type FGF12 for Nav binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated sodium channel complex assembly
• Cardiac conduction
• Neuronal action potential propagation
Protein Summary
FGF12 (FHF1) is a 268-amino acid intracellular protein that belongs to the FHF subfamily. It contains a conserved FGF core domain but lacks a signal peptide. FGF12 directly binds to the C-terminal domain of voltage-gated sodium channels (Nav1.1, Nav1.2, Nav1.5), modulating channel inactivation kinetics and membrane trafficking. It is highly expressed in brain and heart, where it fine-tunes excitability. Mutations cause severe neurological and cardiac disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGF12 Knockout HEK293 Cell Line | EDJ-KQ2137 | Human | 2257 | Details Get a Quote |
| FGF12 Knockout HeLa Cell Line | EDJ-KQ22299 | Human | 2257 | Details Get a Quote |
| FGF12 Knockout H9 Cell Line | EDJ-KZ251 | Human | 2257 | Details Get a Quote |
| FGF12 Knockout A-549 Cell Line | EDJ-KQ61708 | Human | 2257 | Details Get a Quote |
| FGF12 Knockout HCT 116 Cell Line | EDJ-KQ70193 | Human | 2257 | Details Get a Quote |
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