FGF12

Chr 3AD

fibroblast growth factor 12

Also known as: DEE47, EIEE47, FGF12B, FHF1

NCBI Gene: 2257ENSG00000114279UniProt: P61328

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. This growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 47MIM #617166
AD
341
ClinVar variants
45
Pathogenic / LP
0.62
pLI score
0
Active trials
Clinical Summary— FGF12
🧬
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.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 131 VUS of 341 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.54LOEUF
pLI 0.623
Z-score 2.63
OE 0.17 (0.07–0.54)
Moderately 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.
1.52Z-score
OE missense 0.64 (0.54–0.76)
91 obs / 142.1 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.0.17 (0.07–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.54–0.76)
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.0.92
0≤1.21.6
LoF obs/exp: 2 / 11.7Missense obs/exp: 91 / 142.1Syn Z: 0.45

ClinVar Variant Classifications

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic9
VUS131
Likely Benign105
Benign55
Conflicting5
36
Pathogenic
9
Likely Pathogenic
131
VUS
105
Likely Benign
55
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
35
0
36
Likely Pathogenic
1
3
5
0
9
VUS
4
84
42
1
131
Likely Benign
0
16
47
42
105
Benign
0
11
41
3
55
Conflicting
—5
Total511517046341

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

View 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.

Gene2Phenotype Curations

FGF12-related epileptic encephalopathy

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 47

MIM #617166

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FGF12
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss of macrophage fibroblast growth factor 12 attenuates cardiac fibrosis in pressure-overloaded myocardium.
Li S et al.·Int Immunopharmacol
2025
Biallelic structural variations within FGF12 detected by long-read sequencing in epilepsy.
Ohori S et al.·Life Sci Alliance
2023
Modulating effects of FGF12 variants on Na(V)1.2 and Na(V)1.6 being associated with developmental and epileptic encephalopathy and Autism spectrum disorder: A case series.
Seiffert S et al.·EBioMedicine
2022Cohort
FGF12 (Fibroblast Growth Factor 12) Inhibits Vascular Smooth Muscle Cell Remodeling in Pulmonary Arterial Hypertension.
Yeo Y et al.·Hypertension
2020Functional
Long-read sequencing of recurrent FGF12 duplications in epilepsy: Insights into structural mechanisms and aberrant isoforms.
Fauqueux J et al.·Epilepsia
2025Case report
Effective treatments for FGF12-related early-onset epileptic encephalopathies patients.
Tian Q et al.·Brain Dev
2021Case report
Tumorous congenital calcinosis cutis associated with early childhood epileptic encephalopathy with a pathogenic FGF12 gene variant.
Marín-Hernández E et al.·Bol Med Hosp Infant Mex
2020
Depletion of Fibroblast Growth Factor 12 Restrains the Viability, Stemness, and Motility of Colorectal Cancer.
Gao X et al.·Biomed Res Int
2022
FGF12 is a candidate Brugada syndrome locus.
Hennessey JA et al.·Heart Rhythm
2013
HMGN5 promotes invasion and migration of colorectal cancer through activating FGF/FGFR pathway.
Zhu GJ et al.·Eur Rev Med Pharmacol Sci
2021
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools