FGF4

Chr 11AR

fibroblast growth factor 4

Also known as: FGF-4, HBGF-4, HST, HST-1, HSTF-1, HSTF1, K-FGF, KFGF

NCBI Gene: 2249ENSG00000075388UniProt: P08620

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 gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Short-rib thoracic dysplasia 22 without polydactylyMIM #621260
AR
44
ClinVar variants
9
Pathogenic / LP
0.14
pLI score
1
Active trials
Clinical Summary— FGF4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 31 VUS of 44 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.09LOEUF
pLI 0.141
Z-score 1.45
OE 0.35 (0.14–1.09)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.00Z-score
OE missense 0.71 (0.59–0.87)
69 obs / 96.8 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.0.35 (0.14–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.59–0.87)
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.0.98
0≤1.21.6
LoF obs/exp: 2 / 5.8Missense obs/exp: 69 / 96.8Syn Z: 0.09

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS31
Likely Benign2
Benign2
7
Pathogenic
2
Likely Pathogenic
31
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
6
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
28
3
0
31
Likely Benign
0
1
0
1
2
Benign
0
0
2
0
2
Total03013144

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

View in ClinVar →

Protein Context — Lollipop Plot

FGF4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Short-rib thoracic dysplasia 22 without polydactyly

MIM #621260

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FGF4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets.
Schulze K et al.·Nat Genet
2015
Fibroblast Growth Factors in Cardiovascular Disease.
Morita H et al.·J Atheroscler Thromb
2024Review
TNFα prevents FGF4-mediated rescue of astrocyte dysfunction and reactivity in human ALS models.
Velasquez E et al.·Neurobiol Dis
2024Functional
Fibroblast Growth Factors for Nonalcoholic Fatty Liver Disease: Opportunities and Challenges.
Tian H et al.·Int J Mol Sci
2023Review
FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis.
Lin J et al.·J Transl Med
2024
Germ cell cancer.
Oliver RT·Curr Opin Oncol
1999Review
Senescent lung-resident mesenchymal stem cells drive pulmonary fibrogenesis through FGF-4/FOXM1 axis.
Liu Y et al.·Stem Cell Res Ther
2024
Fibroblast Growth Factor-Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications.
Jin L et al.·Annu Rev Pharmacol Toxicol
2023Review
De novo H3.3K27M-altered diffuse midline glioma in human brainstem organoids to dissect GD2 CAR T cell function.
Bessler N et al.·Nat Cancer
2026
Differences Between Sorafenib and Lenvatinib Treatment from Genetic and Clinical Perspectives for Patients with Hepatocellular Carcinoma.
Wang L et al.·Med Sci Monit
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FGF4 alleviates the lung cell damage caused by high glucose via AMPK‑PGC‑1 signaling axis in vitro and in vivo.
Fu Q et al.·Int J Mol Med
2026🔓 Open Access
FGF4-FGFR1 signaling promotes podocyte survival and glomerular function to ameliorate diabetic kidney disease in male mice.
Zhou J et al.·Nat Commun
2025🔓 Open Access
FGF4 drives tumor progression in triple-negative breast cancer via IL6/STAT3-mediated macrophage M2 polarization and immune suppression.
Zhang X et al.·Cell Div
2025🔓 Open Access
Absence of FGF4 Retrogene Insertion on Chromosome 18 Results in a Tall Phenotype in Grand Basset Griffon Vendéen Dogs.
Mhlanga-Mutangadura T et al.·Vet Sci
2025🔓 Open Access
FGF4 alleviates renal injury caused by ischemia-reperfusion(I/R) by inhibiting ferroptosis and pyroptosis.
Ding T et al.·Peptides
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Solid TumorPrecision Medicine

Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

RECRUITING
NCT06739395Phase PHASE2Tianjin Medical University Second HospitalStarted 2024-11-01
Olaparib tabletTemozolomide capsuleAnlotinib

External Resources

Links to major genomics databases and tools