FGF14
Chr 13ADfibroblast growth factor 14
Also known as: FGF-14, FHF-4, FHF4, NYS4, SCA27, SCA27A, SCA27B
This protein is a member of the fibroblast growth factor family involved in nervous system development and function. Mutations cause spinocerebellar ataxia 27A and 27B, with 27B being late-onset, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.39).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
325 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 2 | 110 | 0 | 118 |
Likely Pathogenic | 8 | 0 | 3 | 0 | 11 |
VUS | 6 | 69 | 32 | 5 | 112 |
Likely Benign | 1 | 7 | 18 | 24 | 50 |
Benign | 0 | 0 | 27 | 2 | 29 |
Conflicting | — | 3 | |||
| Total | 21 | 78 | 190 | 31 | 323 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Ataxia GAA-FGF14 - Descriptive Genetic and Clinical Study
ACTIVE NOT RECRUITINGA 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
RECRUITINGExternal Resources
Links to major genomics databases and tools