FGF14

Chr 13AD

fibroblast growth factor 14

Also known as: FGF-14, FHF-4, FHF4, NYS4, SCA27, SCA27A, SCA27B

NCBI Gene: 2259ENSG00000102466UniProt: Q92915

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 27AMIM #193003
AD
Spinocerebellar ataxia 27B, late-onsetMIM #620174
AD
317
ClinVar variants
127
Pathogenic / LP
0.91
pLI score· haploinsufficient
2
Active trials
Clinical Summary— FGF14
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
127 Pathogenic / Likely Pathogenic· 110 VUS of 317 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.909
Z-score 2.96
OE 0.08 (0.03–0.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.76Z-score
OE missense 0.57 (0.47–0.69)
75 obs / 132.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.47–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 1 / 12.1Missense obs/exp: 75 / 132.0Syn Z: 0.26

ClinVar Variant Classifications

317 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
Likely Pathogenic11
VUS110
Likely Benign48
Benign29
Conflicting3
116
Pathogenic
11
Likely Pathogenic
110
VUS
48
Likely Benign
29
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
112
0
116
Likely Pathogenic
8
0
3
0
11
VUS
4
68
33
5
110
Likely Benign
1
7
16
24
48
Benign
0
0
27
2
29
Conflicting
—3
Total167619131317

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FGF14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FGF14-related episodic ataxia

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 27A

MIM #193003

Molecular basis of disorder known

Autosomal dominant

Spinocerebellar ataxia 27B, late-onset

MIM #620174

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FGF14
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia.
Pellerin D et al.·N Engl J Med
2023
Spinocerebellar ataxia 27B: A novel, frequent and potentially treatable ataxia.
Pellerin D et al.·Clin Transl Med
2024Review
Spinocerebellar ataxia 27B (SCA27B), a frequent late-onset cerebellar ataxia.
Clément G et al.·Rev Neurol (Paris)
2024Review
The episodic ataxias.
Graves TD et al.·Handb Clin Neurol
2024Review
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
Coarelli G et al.·Lancet Neurol
2023Review
Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.
Mohren L et al.·Nat Commun
2024
An Update on the Adult-Onset Hereditary Cerebellar Ataxias: Novel Genetic Causes and New Diagnostic Approaches.
Rudaks LI et al.·Cerebellum
2024Review
Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions.
Méreaux JL et al.·EBioMedicine
2024
Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.
Pellerin D et al.·Curr Neurol Neurosci Rep
2025Review
A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus.
Pellerin D et al.·Nat Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Spinocerebellar Ataxia 27B (SCA27B)

A Randomized, Parallel-arm, Double Blind, Placebo-controlled Study to Assess the Efficacy of Fampridine for Patients With Spinocerebellar Ataxia SCA27B Caused by a GAA Expansion in the FGF14 Gene

RECRUITING
NCT07185347Phase PHASE3Assistance Publique - Hôpitaux de ParisStarted 2025-10-21
Fampridine 10 mg prolonged-release tablet (per os)Placebo (tablets per os)
Ataxia, Gait

Ataxia GAA-FGF14 - Descriptive Genetic and Clinical Study

ACTIVE NOT RECRUITING
NCT05884086Central Hospital, Nancy, FranceStarted 2023-05-01

External Resources

Links to major genomics databases and tools