FGF14

Chr 13AD

fibroblast growth factor 14

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

NCBI Gene: 2259ENSG00000102466OMIM: 601515

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.392 OMIM phenotypes
Clinical Summary— FGF14
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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.
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ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 106 VUS of 212 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FGF14
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
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?
1.76Z-score
OE missense 0.57 (0.47–0.69)
75 obs / 132.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.08 (0.03–0.39)
0≤0.351.4
Missense OE?0.57 (0.47–0.69)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 1 / 12.1Missense obs/exp: 75 / 132.0Syn Z: 0.26
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFGF14-related episodic ataxiaLOFAD

This gene — mechanism propensity

DN
0.4586th %ile
GOF
0.6150th %ile
LOF
0.66top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 64% of P/LP variants are LoF · LOEUF 0.39
DN1 literature citation

Literature Evidence

DNIn vitro molecular studies in cultured neurons indicate that the FGF14 (F145S) SCA27 allele acts as a dominant negative mutant suppressing the FGF14 wild type function and resulting in inhibition of voltage-gated Na(+) and Ca(2+) channels.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 26089778 ↗

ClinVar Variant Classifications

212 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic9
VUS106
Likely Benign50
Benign29
Conflicting3
13
Pathogenic
9
Likely Pathogenic
106
VUS
50
Likely Benign
29
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
2
5
0
13
Likely Pathogenic
8
0
1
0
9
VUS
6
69
26
5
106
Likely Benign
1
7
18
24
50
Benign
0
0
27
2
29
Conflicting
—3
Total21787731210

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

View in ClinVar →

107 pathogenic / likely-pathogenic (of 113) ClinVar copy-number / structural variants overlap FGF14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FGF14 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients