What Is FGF14? Definition and What Research Reports
FGF14 (fibroblast growth factor 14, also called FHF4) is an intracellular protein of the fibroblast growth factor homologous factor subfamily, encoded by the human FGF14 gene and expressed mainly in neurons. It is not a secreted signalling peptide and is not used as an injectable research compound. In current literature the term most often refers to the gene locus: a deep intronic GAA repeat expansion in FGF14 was reported as a cause of late-onset cerebellar ataxia, now labelled SCA27B.
Definition
FGF14 (fibroblast growth factor 14) is a protein of the fibroblast growth factor homologous factor (FHF) subfamily, also designated FHF4, and the name of the human gene that encodes it. Despite the “growth factor” label, FGF14 is an intracellular protein: it is not secreted and does not signal through cell-surface FGF receptors in the way that classical FGFs such as FGF1 or FGF21 do. Instead it is described as a neuronal protein that associates with the cytoplasmic tails of voltage-gated sodium channels, with prominent expression in the cerebellum. In most contemporary publications the term FGF14 refers to the gene locus rather than to a purified protein, because a deep intronic GAA repeat expansion in intron 1 of FGF14 was reported as a cause of late-onset cerebellar ataxia (PMID 36516086).
Molecule Class and Origin
FGF14 belongs to the fibroblast growth factor superfamily by sequence homology, but it is grouped with the intracellular FHF branch (FHF1–FHF4) rather than the paracrine or endocrine branches. It is a full protein of a few hundred amino acids, not a short synthetic peptide, and it is produced endogenously from the FGF14 gene in human and animal tissue. Its best-characterised setting is the central nervous system, where cerebellar Purkinje neurons are the cell type most often discussed in the ataxia literature (PMID 36516086). There is no approved FGF14 drug product, and FGF14 is not one of the synthetic peptides that appear in research-chemical catalogues; readers who encounter the term almost always encounter it as a genetic finding.
How the Term Is Used in Peptide and Biomedical Research
Three distinct usages appear in the published record:
- As a gene and repeat locus. The dominant usage. Papers refer to “GAA-FGF14” expansions, “the FGF14 repeat locus,” or the disease label SCA27B (spinocerebellar ataxia type 27B) (PMID 37165652).
- As an intracellular protein partner of ion channels. Here FGF14 is treated as a structural and regulatory protein of neuronal excitability rather than as a secreted growth factor.
- As a signalling-pathway node outside the nervous system. One study examined FGF14 in colorectal cancer cells and reported that it acted as a tumour suppressor through inhibition of the PI3K/AKT/mTOR pathway (PMID 31949485).
None of the verified literature below describes FGF14 being administered to humans or animals as a peptide therapeutic. Discussion of the molecule in the clinical literature is genetic and observational.
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The 2023 report in The New England Journal of Medicine described a deep intronic GAA repeat expansion in FGF14 in patients with late-onset cerebellar ataxia, and researchers identified this expansion as a frequent genetic cause in the cohorts they examined (PMID 36516086). A companion 2023 study in Brain characterised the phenotypic profile and natural-history progression of GAA-FGF14 ataxia (SCA27B) and also reported on 4-aminopyridine treatment response in affected individuals (PMID 37165652). Since then the locus has been examined in multiple populations: a large Chinese cohort study described the genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia (PMID 38513302), and a 2025 study in Indian ataxia patients reported unstable FGF14 GAA expansions, a broader phenotype and possible involvement of modifier loci (PMID 40835733).
Repeat stability and genetic modifiers
Because the pathogenic element is a tandem repeat, several papers have focused on how stable that repeat is across generations and within tissues. A 2024 Nature Genetics study reported that a common flanking variant was associated with enhanced stability of the FGF14–SCA27B repeat locus (PMID 38937606). A 2025 Brain paper asked whether repeat length and mosaic interruptions act as modifiers of SCA27B (PMID 40379261), and a 2024 study examined characteristics of tandem repeat inheritance alongside sympathetic nerve involvement in GAA-FGF14 ataxia (PMID 38866925).
Beyond classic ataxia
The locus has also been examined in other neurological conditions. Researchers reported that intronic FGF14 GAA repeat expansions had an impact on progression and survival in multiple system atrophy (PMID 40239008). A 2025 report described phenotypic overlap between GAA-FGF14 expansions and CACNA1A variants, together with the diagnostic implications of that overlap (PMID 40879304). A further paper described a complex FGF14 (TTC)/(TGC) repeat expansion identified in Parkinson's disease (PMID 41277530).
| Study focus | Journal, year | What researchers reported |
|---|---|---|
| Deep intronic GAA expansion | NEJM, 2023 | Identified a deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia (PMID 36516086) |
| Phenotype and natural history | Brain, 2023 | Described the SCA27B phenotypic profile, progression and 4-aminopyridine treatment response (PMID 37165652) |
| Chinese cohort | EBioMedicine, 2024 | Mapped the genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia (PMID 38513302) |
| Repeat stability | Nature Genetics, 2024 | A common flanking variant was associated with enhanced repeat-locus stability (PMID 38937606) |
| Multiple system atrophy | Brain, 2025 | Intronic GAA expansions impacted progression and survival in MSA (PMID 40239008) |
| Colorectal cancer cells | Journal of Cancer, 2020 | FGF14 functioned as a tumour suppressor through PI3K/AKT/mTOR inhibition (PMID 31949485) |
Associated Clinical Features and Adverse Events: What Studies Report
Because FGF14 is not administered as a compound in the verified literature, there are no administration-related adverse events to summarise. What the studies describe instead are clinical features associated with the expanded repeat. The 2023 Brain natural-history study reported the phenotypic profile and progression of GAA-FGF14 ataxia and included data on 4-aminopyridine treatment response (PMID 37165652). A 2025 European Journal of Neurology study examined neuropathy in GAA-FGF14 late-onset cerebellar ataxia and reported its prevalence and characteristics in the cohort studied (PMID 40579842). Autonomic involvement has also been examined, with one study reporting sympathetic nerve involvement alongside tandem repeat inheritance patterns (PMID 38866925). Broader or atypical presentations were described in the Indian cohort report (PMID 40835733) and in the paper on overlap with CACNA1A variants (PMID 40879304).
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Readers arriving from other fibroblast growth factor entries should note the distinction. Endocrine FGFs such as FGF21 circulate and bind receptors; FGF14 belongs to the intracellular FHF group and is not described that way in the literature cited here. Practically, this means FGF14 does not appear in the literature as a compound with a dose, a route of administration or a duration of exposure, and no such figures are reported in the papers listed on this page. Where the name appears in a clinical report, it almost always refers to genotyping of the repeat locus (PMID 36516086).
Scope and Limitations
This entry is definitional. It does not describe eligibility for testing, interpretation of a genetic result, prognosis, or any treatment decision. Repeat-expansion findings vary by population and by laboratory method, and the cited studies were conducted in different cohorts with different ascertainment, so results in one population should not be assumed to transfer to another (PMID 38513302). This page is for educational purposes only and is not medical advice; consult a licensed physician or qualified genetic counsellor about any medical or genetic question.
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- Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia (The New England Journal of Medicine, 2023)
- GAA-FGF14 ataxia (SCA27B): phenotypic profile, natural history progression and 4-aminopyridine treatment response (Brain, 2023)
- The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study (EBioMedicine, 2024)
- A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus (Nature Genetics, 2024)
- FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B? (Brain, 2025)
- Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia (Journal of Human Genetics, 2024)
- Unstable FGF14 GAA repeat expansions in Indian ataxia patients: a broader phenotype and involvement of modifier loci? (Journal of Human Genetics, 2025)
- Neuropathy in GAA-FGF14 Late-Onset Cerebellar Ataxia (SCA27B): Prevalence and Characteristics (European Journal of Neurology, 2025)
- Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy (Brain, 2025)
- GAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications (Movement Disorders, 2025)
- A Complex FGF14 (TTC)/(TGC) Repeat Expansion in Parkinson's Disease (Movement Disorders, 2026)
- FGF14 Functions as a Tumor Suppressor through Inhibiting PI3K/AKT/mTOR Pathway in Colorectal Cancer (Journal of Cancer, 2020)
Frequently asked questions
Is FGF14 a peptide?▾
Not in the sense used for synthetic research peptides. FGF14 is a full intracellular protein of the fibroblast growth factor homologous factor subfamily, encoded by the human FGF14 gene. It is not secreted and is not administered as a compound in the literature cited here, where it appears mainly as a repeat-expansion locus in late-onset cerebellar ataxia (PMID 36516086).},
What is SCA27B?▾
SCA27B is the disease label applied to ataxia caused by a deep intronic GAA repeat expansion in the FGF14 gene, first described in a 2023 report on late-onset cerebellar ataxia (PMID 36516086). A 2023 study in Brain characterised its phenotypic profile, natural-history progression and 4-aminopyridine treatment response (PMID 37165652).
Has FGF14 been studied outside the nervous system?▾
Yes. A 2020 laboratory study in colorectal cancer reported that FGF14 functioned as a tumour suppressor by inhibiting the PI3K/AKT/mTOR pathway (PMID 31949485). That work concerned endogenous FGF14 expression in cancer cells rather than administration of FGF14 as a therapeutic agent, and it sits apart from the neurological literature.
Why do studies focus on repeat stability at the FGF14 locus?▾
Because the pathogenic element is a tandem repeat whose length can change. Researchers reported that a common flanking variant was associated with enhanced stability of the FGF14-SCA27B repeat locus (PMID 38937606), while another 2025 analysis examined whether repeat length and mosaic interruptions act as modifiers of SCA27B (PMID 40379261).
Has FGF14 been linked to conditions other than cerebellar ataxia?▾
Published reports have examined it in several settings. One study reported that intronic FGF14 GAA repeat expansions impacted progression and survival in multiple system atrophy (PMID 40239008), and a separate paper described a complex FGF14 (TTC)/(TGC) repeat expansion in Parkinson's disease (PMID 41277530). These are observational genetic findings, not treatment studies.
What non-cerebellar features have studies described?▾
A 2025 study examined neuropathy in GAA-FGF14 late-onset cerebellar ataxia and reported its prevalence and characteristics (PMID 40579842). A 2024 paper reported sympathetic nerve involvement alongside tandem repeat inheritance patterns (PMID 38866925), and a cohort from India described a broader phenotype with possible modifier loci (PMID 40835733).
Do findings differ between populations?▾
The cited cohorts differ in ascertainment and method. A large Chinese cohort study described the genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in that population (PMID 38513302), while a separate 2025 report described unstable expansions and a broader phenotype in Indian ataxia patients (PMID 40835733). Comparisons across such cohorts should be made cautiously.
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References
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.