FGF4: Fibroblast Growth Factor 4
A key regulator of embryonic development, cell proliferation, and oncogenic signaling
Gene Information Card
| Symbol | FGF4 |
|---|---|
| Full Name | Fibroblast growth factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.3 |
| NCBI Gene ID | 2249 ncbi.nlm.nih.gov/gene/2249 |
| Ensembl ID | ENSG00000075388 |
| UniProt ID | P08620 |
| OMIM ID | 164980 |
| HGNC ID | 3685 |
| Aliases | HST, HSTF1, HBGF-4, FGF-4, K-FGF, HST-1 |
Description
FGF4 (fibroblast growth factor 4) encodes a member of the fibroblast growth factor (FGF) family. The encoded protein functions as a secreted signaling molecule that binds to FGF receptors (FGFRs) to regulate cell proliferation, differentiation, and migration. FGF4 plays critical roles in embryonic development, particularly in limb formation and inner cell mass proliferation. Aberrant expression and mutations of FGF4 are implicated in various cancers, including breast, gastric, and hepatocellular carcinomas, as well as in developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | FGF4 amplification and overexpression lead to constitutive FGFR signaling, promoting tumor cell proliferation and survival. | COSMIC, ClinVar |
| Gastric cancer | FGF4 gene amplification and protein overexpression activate MAPK/ERK and PI3K/AKT pathways, driving oncogenesis. | COSMIC, NCBI |
| Hepatocellular carcinoma | FGF4 overexpression via gene amplification enhances autocrine/paracrine FGFR signaling, contributing to tumor growth and metastasis. | COSMIC, PubMed |
| Lung cancer | FGF4 amplification and activating mutations promote FGFR-dependent signaling, associated with poor prognosis. | COSMIC, ClinVar |
| Kaposi sarcoma | FGF4 expression is upregulated and contributes to angiogenesis and tumor progression. | NCBI, PubMed |
| Limb malformation (e.g., syndactyly) | Gain-of-function mutations in FGF4 disrupt normal limb bud patterning, leading to digit fusion. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Placenta | 8.7 | Low |
| Brain | 2.1 | Not detected |
| Heart | 1.5 | Not detected |
| Liver | 0.8 | Not detected |
| Kidney | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.6 | Moderate expression |
| MCF7 (breast carcinoma) | 22.4 | High expression |
| A549 (lung carcinoma) | 9.8 | Low expression |
| HepG2 (hepatocellular carcinoma) | 18.3 | Moderate expression |
| K562 (leukemia) | 3.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.314A>G (p.Tyr105Cys) | Missense | <0.1% | Gain-of-function; increased FGFR binding affinity |
| c.482G>A (p.Arg161Gln) | Missense | <0.1% | Unknown functional effect |
| Amplification (11q13.3) | Copy number gain | Variable (5-20% in cancers) | Overexpression; oncogenic driver |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Loss of function; reduced protein expression |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) reduce or abolish FGF4 protein expression, impairing signaling.
Gain of Function (GOF)
Missense mutations (e.g., p.Tyr105Cys) enhance receptor binding and downstream signaling, promoting oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations reported for FGF4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Ras signaling pathway (KEGG: hsa04014)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• FGF signaling pathway (Reactome: R-HSA-190236)
• Signaling by FGFR (Reactome: R-HSA-190237)
Protein Summary
FGF4 is a 206-amino acid secreted glycoprotein (UniProt P08620) belonging to the FGF family. It contains a conserved FGF domain and a signal peptide for secretion. The mature protein binds to FGFR1-4 with high affinity, particularly FGFR1c and FGFR2c, inducing receptor dimerization and autophosphorylation. This activates downstream cascades including MAPK/ERK, PI3K/AKT, and PLCγ pathways. FGF4 is critical for embryonic development (limb bud formation, inner cell mass proliferation) and is implicated in oncogenesis when aberrantly expressed or mutated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGF4 Knockout HEK293 Cell Line | EDJ-KQ50272 | Human | 2249 | Details Get a Quote |
| FGF4 Knockout HeLa Cell Line | EDJ-KQ53222 | Human | 2249 | Details Get a Quote |
| FGF4 Knockout A-549 Cell Line | EDJ-KQ61700 | Human | 2249 | Details Get a Quote |
| FGF4 Knockout HCT 116 Cell Line | EDJ-KQ70188 | Human | 2249 | Details Get a Quote |
