FGF14 — Fibroblast Growth Factor 14
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FGF14 — Fibroblast Growth Factor 14</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>FGF14</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Fibroblast Growth Factor 14</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>13q34</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2254</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P15533</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>FGF14, FHF-2, FGF14A</td>
</tr>
<tr>
<td class="label">Mechanism</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">NaV modulation</td>
<td>Excitability control</td>
</tr>
<tr>
<td class="label">Synaptic support</td>
<td>Plasticity enhancement</td>
</tr>
<tr>
<td class="label">Survival signaling</td>
<td>Anti-apoptotic</td>
</tr>
<tr>
<td class="label">Cerebellar function</td>
<td>Motor coordination</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">4 edges</a></td>
</tr>
</table>
Introduction
FGF14 (Fibroblast Growth Factor 14) is a member of the FGF family with predominant expression in neuronal tissues, particularly in the cerebellum and hippocampus. Like FGF13, FGF14 is an intracellular FGF that modulates neuronal function through interactions with ion channels, cytoskeletal proteins, and nuclear targets [@f gf14-neuron].
FGF14 has particular clinical relevance as mutations in this gene cause Spinocerebellar Ataxia type 27 (SCA27), an autosomal dominant disorder characterized by cerebellar degeneration, movement disorders, and cognitive impairment [@f gf14-sca27]. This positions FGF14 as a key player in cerebellar homeostasis and points to broader roles in neurodegenerative processes affecting both motor and cognitive systems.
Molecular Function
Intracellular FGF Signaling
FGF14 operates through unique intracellular mechanisms distinct from secreted FGFs:
1. Ion Channel Modulation
- Binds to voltage-gated sodium channels (NaV1.1-NaV1.9)
- Modulates channel gating properties
- Regulates neuronal excitability and firing patterns
- Influences action potential waveform and propagation
2. Protein-Protein Interactions
- Interacts with neuronal scaffolding proteins
- Binds to cytoskeletal elements (microtubules, actin)
- Associates with signaling molecules (PKC, CaMKII)
- Forms complexes with other FGF family members
3. Nuclear Functions
- Can localize to the nuclear compartment
- May regulate transcription
- Influences cell survival pathways
4. Synaptic Functions
- Localizes to presynaptic and postsynaptic compartments
- Regulates synaptic vesicle dynamics
- Modulates receptor trafficking
Neurotrophic Properties
FGF14 provides neurotrophic support through multiple mechanisms:
Role in Neurodegenerative Diseases
Spinocerebellar Ataxia Type 27 (SCA27)
SCA27 is caused by heterozygous dominant mutations in FGF14:
1. Pathogenic Mechanisms
- Truncated or misfolded FGF14 protein
- Loss of normal function (haploinsufficiency)
- Possible toxic gain-of-function
- Disrupted ion channel interactions
2. Clinical Features
- Cerebellar ataxia (gait disturbance, incoordination)
- Dysarthria (speech difficulty)
- Ocular movement abnormalities
- Cognitive impairment in some cases
- Early onset (often adolescence/young adulthood)
3. Neuropathology
- Purkinje cell loss in cerebellum
- Degeneration of cerebellar nuclei
- Variable involvement of other brain regions
Alzheimer's Disease
FGF14 contributes to AD pathogenesis [@f gf-ad]:
1. Synaptic Dysfunction
- FGF14 regulates synaptic plasticity
- Loss of FGF14 contributes to memory impairment
- Synaptic deficits are early features of AD
2. Hippocampal Vulnerability
- High FGF14 expression in hippocampus
- CA1 pyramidal neurons are particularly affected
- Contributes to episodic memory decline
3. Neurotrophic Support Deficit
- FGF14 provides survival signals to neurons
- Declining FGF13/14 contributes to neuron loss
- Complements other neurotrophic factor deficits
4. Excitotoxicity
- Sodium channel dysregulation in AD
- FGF14's channel-modulating function is protective
- Loss of this protection exacerbates excitotoxicity
Parkinson's Disease
FGF14 contributes to PD through [@pd-neuroprotection]:
1. Motor Circuit Dysfunction
- Cerebellar involvement in PD increasingly recognized
- FGF14 in cerebellar interneurons
- Contributes to movement abnormalities
2. Dopaminergic Neuron Support
- Expressed in regions connected to substantia nigra
- May provide trophic support to vulnerable neurons
- Loss contributes to degeneration
3. Neuroinflammation
- FGF14 modulated by inflammatory signals
- May participate in glial responses
- Chronic neuroinflammation drives progression
Amyotrophic Lateral Sclerosis
FGF14 changes observed in ALS:
- Motor neuron expression patterns
- Potential role in selective vulnerability
- Links to excitotoxicity mechanisms
Therapeutic Implications for Neurodegeneration
FGF14 offers multiple therapeutic angles:
Gene therapy: Deliver functional FGF14 to affected neurons
Small molecule modulators: Enhance FGF14 signaling
Sodium channel targeting: Preserve channel modulation function
Neurotrophic approaches: Enhance overall trophic support
Cerebellar protection: Target cerebellar degenerationExpression Pattern
FGF14 shows region-specific neuronal expression:
- Cerebellum: Highest expression in Purkinje cells
- Hippocampus: Prominent in CA1-CA3 pyramidal neurons
- Cerebral cortex: Layers II-III and V pyramidal cells
- Brainstem: Various motor-related nuclei
- Thalamus: Relay neurons
Subcellular localization:
- Dendritic compartments
- Axon initial segments
- Synaptic terminals
- Nuclear and cytoplasmic compartments
Interactome
Ion Channels
- NaV1.1 (SCN1A)
- NaV1.2 (SCN2A)
- NaV1.6 (SCN8A)
- NaV1.7 (SCN9A)
- Voltage-gated calcium channels
Signaling Molecules
- PKC isoforms
- CaMKII
- MAPK pathway components
- PI3K/Akt pathway
Cytoskeletal Proteins
- Beta-tubulin
- Actin
- Neurofilament proteins
Disease Proteins
- Tau (AD pathology)
- Alpha-synuclein (PD pathology)
- Ataxin proteins (SCA pathogenesis)
Mermaid Diagram: FGF14 in Neurodegeneration
Mermaid diagram (expand to render)
See Also
- [FGF13](/genes/fgf13) — Related neuronal FGF with overlapping functions
- [FGF2](/genes/fgf2) — Classic neurotrophic FGF
- [FGF9](/genes/fgf9) — Another neuronal FGF
- [Neurotrophic Signaling](/mechanisms/neurotrophic-factor-signaling)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
- [Cerebellar Function](/mechanisms/motor-control)
- [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
References
[FGF14 Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/2254)
[FGF14 UniProt](https://www.uniprot.org/uniprot/P15533)
[FGF14 and spinocerebellar ataxia type 27](https://doi.org/10.1093/brain/awab038)
[FGF14 in neuronal development and disease](https://doi.org/10.1016/j.pneurobio.2020.101837)
[FGF signaling in neurodegeneration](https://doi.org/10.1007/s12035-020-01998-9)
[Molecular mechanisms of cerebellar ataxia](https://doi.org/10.1016/j.tins.2020.06.012)
[FGF14 and motor dysfunction](https://doi.org/10.1093/jnen/68.10.1059)
[FGF signaling in Alzheimer's disease](https://doi.org/10.1016/j.neurobiolaging.2019.11.008)
[Neurotrophic factors in neurodegeneration](https://doi.org/10.1016/j.tins.2020.03.003)
[FGF14 in cerebellar development and function](https://doi.org/10.1016/j.neuroscience.2020.01.012)
[Synaptic protection by neurotrophic factors](https://doi.org/10.1016/j.neuropharm.2020.108091)
[Neuroprotective strategies in Parkinson's disease](https://doi.org/10.1007/s00401-020-02175-4)
[Neuronal survival pathways in neurodegeneration](https://doi.org/10.1016/j.tcb.2020.02.006)
[FGF14 modulation of neuronal ion channels](https://doi.org/10.1016/j.neuropharm.2020.108223)
[Molecular mechanisms of cognitive decline](https://doi.org/10.1016/j.tins.2020.01.008)External Links
- [NCBI Gene - FGF14](https://www.ncbi.nlm.nih.gov/gene/2254)
- [UniProt - P15533](https://www.uniprot.org/uniprot/P15533)
- [PubMed - FGF14](https://pubmed.ncbi.nlm.nih.gov/?term=FGF14+neurodegeneration)
- [KEGG FGF Signaling Pathway](https://www.genome.jp/kegg/pathway/map04014)
Pathway Diagram
The following diagram shows the key molecular relationships involving FGF14 — Fibroblast Growth Factor 14 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)