FGFR4: Fibroblast Growth Factor Receptor 4
A receptor tyrosine kinase involved in development, metabolism, and cancer
Gene Information Card
| Symbol | FGFR4 |
|---|---|
| Full Name | Fibroblast growth factor receptor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.2 |
| NCBI Gene ID | 2264 ncbi.nlm.nih.gov/gene/2264 |
| Ensembl ID | ENSG00000160867 |
| UniProt ID | P22455 |
| OMIM ID | 134935 |
| HGNC ID | 3691 |
| Aliases | CD334, JTK2, TKF |
Description
FGFR4 (fibroblast growth factor receptor 4) is a member of the fibroblast growth factor receptor family, encoding a receptor tyrosine kinase that binds fibroblast growth factors (FGFs). It plays a critical role in cell proliferation, differentiation, migration, and survival. FGFR4 is involved in embryonic development, tissue repair, and metabolic regulation. Aberrant FGFR4 signaling, including mutations and overexpression, is implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Activating mutations (e.g., G388R) enhance receptor signaling, promoting tumor growth and metastasis | ClinVar, COSMIC |
| Breast cancer | Overexpression and gain-of-function variants (e.g., G388R) associated with poor prognosis and resistance to therapy | ClinVar, COSMIC |
| Prostate cancer | FGFR4 amplification and activating mutations drive oncogenic signaling | COSMIC |
| Rhabdomyosarcoma | FGFR4 mutations (e.g., K535E, E550K) lead to constitutive activation and tumor progression | COSMIC, ClinVar |
| Metabolic syndrome | FGFR4 variants (e.g., G388R) linked to altered lipid metabolism and insulin resistance | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Lung | 6.1 | Low |
| Breast | 4.7 | Low |
| Prostate | 3.9 | Low |
| Muscle | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 15.2 | High expression |
| MCF7 (breast cancer) | 8.9 | Moderate expression |
| A549 (lung cancer) | 6.4 | Low expression |
| PC3 (prostate cancer) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G388R | Missense | ~5-10% in various cancers | Gain-of-function; increases receptor stability and signaling |
| K535E | Missense | Rare in rhabdomyosarcoma | Gain-of-function; constitutive activation |
| E550K | Missense | Rare in rhabdomyosarcoma | Gain-of-function; constitutive activation |
| V550L | Missense | Rare in cancer | Gain-of-function; enhanced kinase activity |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in human disease.
Gain of Function (GOF)
G388R, K535E, E550K, V550L: increase receptor autophosphorylation and downstream signaling (MAPK/ERK, PI3K/AKT).
Dominant Negative (DN)
Not reported for FGFR4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• FGF signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Ras signaling pathway (KEGG: hsa04014)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
FGFR4 is a 802-amino acid receptor tyrosine kinase with an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. It binds FGF ligands (e.g., FGF1, FGF2, FGF19) and activates downstream signaling cascades including MAPK/ERK and PI3K/AKT. The protein is highly expressed in liver and kidney, and its dysregulation contributes to cancer progression and metabolic disorders. The G388R polymorphism is a common gain-of-function variant associated with poor prognosis in multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGFR4 Knockout HEK293 Cell Line | EDJ-KQ17698 | Human | 2264 | Details Get a Quote |
| FGFR4 Knockout A-549 Cell Line | EDJ-KQ19182 | Human | 2264 | Details Get a Quote |
| FGFR4 Knockout HCT 116 Cell Line | EDJ-KQ19183 | Human | 2264 | Details Get a Quote |
| FGFR4 Knockout HeLa Cell Line | EDJ-KQ19184 | Human | 2264 | Details Get a Quote |
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