FGF11

Chr 17

fibroblast growth factor 11

Also known as: FGF-11, FHF-3, FHF3

NCBI Gene: 2256 ENSG00000161958 UniProt: Q92914 OMIM: 601514

The protein is probably involved in nervous system development and function. Mutations cause autosomal dominant episodic ataxia type 9, characterized by episodes of imbalance and incoordination. This gene is highly constrained against loss-of-function variants, suggesting intolerance to complete protein loss.

OMIM ResearchSummary from UniProt

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. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.27

Clinical Summary— FGF11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 47 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.96

OE 0.68 (0.38–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.91 (0.78–1.06)

115 obs / 126.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.38–1.27)

0≤0.351.4

Missense OE?0.91 (0.78–1.06)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 7 / 10.3Missense obs/exp: 115 / 126.6Syn Z: 0.74

This gene — mechanism propensity

0.6453th %ile

GOF

0.6932th %ile

LOF

0.3745th %ile

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

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Benign2

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	39	0	39
Likely Benign	0	0	0
Benign	0	2	2
Total	39	2	41

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap FGF11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →