FGF9: Fibroblast Growth Factor 9
A key regulator of skeletal development, gonadal differentiation, and glial cell growth; implicated in multiple synostosis syndrome and cancers.
Gene Information Card
| Symbol | FGF9 |
|---|---|
| Full Name | Fibroblast Growth Factor 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q12.11 |
| NCBI Gene ID | 2254 ncbi.nlm.nih.gov/gene/2254 |
| Ensembl ID | ENSG00000102678 |
| UniProt ID | P31371 |
| OMIM ID | 600921 |
| HGNC ID | 3687 |
| Aliases | GAF, HBFG-9, SYNS3 |
Description
FGF9 (Fibroblast Growth Factor 9) encodes a member of the fibroblast growth factor (FGF) family. The encoded protein plays a critical role in embryonic development, particularly in skeletal formation, inner ear morphogenesis, and gonadal differentiation. It acts as a ligand for FGF receptors (FGFRs) and is involved in cell proliferation, differentiation, and survival. Mutations in FGF9 are associated with multiple synostosis syndrome 3 (SYNS3) and have been implicated in various cancers, including lung, prostate, and colorectal cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple synostosis syndrome 3 (SYNS3) | Missense mutations (e.g., p.Ser99Pro, p.Gly170Arg) impair FGF9 dimerization and receptor binding, leading to abnormal bone fusion and joint development. | OMIM #612961; ClinVar |
| Prostate cancer | FGF9 overexpression promotes androgen-independent growth and tumor progression via autocrine/paracrine FGFR signaling. | COSMIC; PubMed studies |
| Lung cancer | FGF9 amplification and overexpression contribute to tumor cell proliferation and angiogenesis. | COSMIC; PubMed studies |
| Colorectal cancer | FGF9 upregulation correlates with poor prognosis and may drive epithelial-mesenchymal transition. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 4.2 | Low |
| Heart | 1.8 | Low |
| Kidney | 3.5 | Low |
| Liver | 0.9 | Not detected |
| Lung | 6.7 | Medium |
| Ovary | 8.1 | Medium |
| Testis | 12.3 | High |
| Uterus | 5.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 8.5 | High expression |
| PC-3 (prostate cancer) | 10.2 | High expression |
| MCF7 (breast cancer) | 3.1 | Low expression |
| HCT116 (colorectal carcinoma) | 6.8 | Medium expression |
| HEK293 (embryonic kidney) | 2.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.295T>C (p.Ser99Pro) | Missense | Rare | Impairs FGF9 dimerization; causes SYNS3 |
| c.508G>A (p.Gly170Arg) | Missense | Rare | Disrupts FGFR binding; causes SYNS3 |
| c.382G>A (p.Glu128Lys) | Missense | Rare | Associated with SYNS3 |
| Amplification | Copy number gain | Frequent in lung cancer | Overexpression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FGF9 are not well characterized; most pathogenic missense variants (e.g., p.Ser99Pro) are considered hypomorphic or dominant-negative, reducing but not abolishing signaling.
Gain of Function (GOF)
Gene amplification and overexpression in cancers (e.g., lung, prostate) lead to gain-of-function through increased ligand availability and sustained FGFR activation.
Dominant Negative (DN)
Missense mutations such as p.Ser99Pro and p.Gly170Arg act in a dominant-negative manner by disrupting FGF9 dimerization, thereby reducing functional ligand available for receptor binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (Reactome: R-HSA-5673001)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• FGFR signaling pathway (Reactome: R-HSA-190236)
• Signaling by FGFR in disease (Reactome: R-HSA-5655253)
Protein Summary
FGF9 is a 208-amino acid secreted protein (UniProt P31371) that functions as a homodimer. It binds to and activates FGFR1c, FGFR2c, FGFR3c, and FGFR4, with high affinity for FGFR3c. The protein is involved in multiple developmental processes, including bone formation, inner ear development, and testicular differentiation. In adults, it is expressed in the brain, lung, kidney, and reproductive tissues. Aberrant FGF9 signaling contributes to skeletal disorders and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGF9 Knockout HEK293 Cell Line | EDJ-KQ665 | Human | 2254 | Details Get a Quote |
| FGF9 Knockout HCT 116 Cell Line | EDJ-KQ19174 | Human | 2254 | Details Get a Quote |
| FGF9 Knockout HeLa Cell Line | EDJ-KQ53227 | Human | 2254 | Details Get a Quote |
| FGF9 Knockout A-549 Cell Line | EDJ-KQ61705 | Human | 2254 | Details Get a Quote |
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