FGF12

Chr 3AD

fibroblast growth factor 12

Also known as: DEE47, EIEE47, FGF12B, FHF1

The protein is a member of the fibroblast growth factor family that lacks a signal sequence and instead localizes to the nucleus rather than being secreted. Mutations cause developmental and epileptic encephalopathy 47 through an autosomal dominant inheritance pattern. The specific mechanism by which nuclear FGF12 dysfunction leads to seizures and developmental delay remains unclear.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.541 OMIM phenotype
Clinical SummaryFGF12
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.623
Z-score 2.63
OE 0.17 (0.070.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.52Z-score
OE missense 0.64 (0.540.76)
91 obs / 142.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.070.54)
00.351.4
Missense OE0.64 (0.540.76)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 2 / 11.7Missense obs/exp: 91 / 142.1Syn Z: 0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFGF12-related epileptic encephalopathyGOFAD
DN
0.5180th %ile
GOF
0.6442th %ile
LOF
0.59top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median · 1 literature citation

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.

Literature Evidence

GOFGain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophyPMID:27164707

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FGF12 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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