FGFR2 Gene (Fibroblast Growth Factor Receptor 2): Structure, Function, and Clinical Significance
A comprehensive overview of FGFR2, its associated diseases, expression patterns, mutations, and molecular functions.
Gene Information Card
| Symbol | FGFR2 |
|---|---|
| Full Name | Fibroblast growth factor receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 2263 ncbi.nlm.nih.gov/gene/2263 |
| Ensembl ID | ENSG00000066468 |
| UniProt ID | P21802 |
| OMIM ID | 176943 |
| HGNC ID | 3689 |
| Aliases | BEK, BFR-1, CEK3, CFD1, ECT1, KGFR, TK14, K-SAM |
Description
FGFR2 encodes fibroblast growth factor receptor 2, a transmembrane receptor tyrosine kinase that binds fibroblast growth factors (FGFs) and regulates cellular processes such as proliferation, differentiation, migration, and survival. Alternative splicing generates multiple isoforms with distinct ligand-binding specificities. Mutations in FGFR2 are associated with various developmental disorders and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Craniosynostosis syndromes (e.g., Apert, Crouzon, Pfeiffer) | Gain-of-function mutations in FGFR2 lead to constitutive activation or altered ligand specificity, causing premature fusion of cranial sutures. | ClinVar, OMIM |
| Prostate cancer | Somatic mutations and amplifications of FGFR2 contribute to tumor progression and metastasis. | COSMIC, ClinVar |
| Gastric cancer | FGFR2 amplification and overexpression drive tumor cell proliferation and survival. | COSMIC, ClinVar |
| Endometrial cancer | Activating mutations and fusions involving FGFR2 promote oncogenic signaling. | COSMIC, ClinVar |
| Lung cancer | FGFR2 alterations, including mutations and amplifications, are implicated in tumorigenesis. | COSMIC, ClinVar |
| Lacrimo-auriculo-dento-digital (LADD) syndrome | Loss-of-function mutations in FGFR2 disrupt normal development of lacrimal and salivary glands, ears, and digits. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.7 | Medium |
| Kidney | 10.2 | Medium |
| Lung | 9.8 | Medium |
| Stomach | 8.5 | Low |
| Breast | 7.9 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | High expression; associated with hormone-responsive growth |
| A549 (lung cancer) | 12.1 | Moderate expression; may contribute to proliferation |
| K562 (leukemia) | 5.4 | Low expression; minimal role in this lineage |
| HepG2 (liver cancer) | 8.7 | Moderate expression; potential target in hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| S252W | Missense | Common in Apert syndrome (~66% of cases) | Gain-of-function; alters ligand binding and receptor activation |
| P253R | Missense | Common in Apert syndrome (~33% of cases) | Gain-of-function; similar effect to S252W |
| C278F | Missense | Found in Crouzon syndrome | Gain-of-function; promotes receptor dimerization |
| C342R | Missense | Found in Crouzon and Pfeiffer syndromes | Gain-of-function; enhances receptor signaling |
| N549K | Missense | Somatic in endometrial cancer | Gain-of-function; constitutive kinase activity |
| K310R | Missense | Somatic in gastric cancer | Gain-of-function; increased signaling |
| FGFR2 amplification | Copy number gain | Observed in gastric and breast cancers | Overexpression; drives oncogenic signaling |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FGFR2 are rare but can cause LADD syndrome, leading to reduced receptor signaling and developmental defects.
Gain of Function (GOF)
Most pathogenic mutations are gain-of-function, leading to constitutive activation or altered ligand specificity, contributing to craniosynostosis and cancer.
Dominant Negative (DN)
Dominant-negative effects have been reported in some FGFR2 mutations, where mutant receptors interfere with wild-type signaling, though less common.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • fibroblast growth factor binding |
| • fibroblast growth factor-activated receptor activity | • protein tyrosine kinase activity |
| • transmembrane receptor protein tyrosine kinase signaling pathway | • cell proliferation |
| • cell differentiation | • positive regulation of cell migration |
| • MAPK cascade | • PI3K-Akt signaling pathway |
Pathways
• FGF signaling pathway
• MAPK/ERK signaling pathway
• PI3K-Akt signaling pathway
• Ras signaling pathway
• PLC-gamma signaling pathway
• Regulation of cell cycle
Protein Summary
FGFR2 is a single-pass type I transmembrane protein with an extracellular region containing three immunoglobulin-like domains, a transmembrane helix, and an intracellular tyrosine kinase domain. Upon FGF binding, FGFR2 dimerizes and autophosphorylates, activating downstream signaling cascades such as RAS-MAPK, PI3K-AKT, and PLCγ. Isoforms (IIIb and IIIc) are expressed in epithelial and mesenchymal tissues, respectively, and determine ligand specificity. The protein plays critical roles in development, tissue repair, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGFR2 Knockout HEK293 Cell Line | EDJ-KQ17682 | Human | 2263 | Details Get a Quote |
| FGFR2 Knockout HCT 116 Cell Line | EDJ-KQ18098 | Human | 2263 | Details Get a Quote |
| FGFR2 Knockout HeLa Cell Line | EDJ-KQ53231 | Human | 2263 | Details Get a Quote |
| FGFR2 Knockout A-549 Cell Line | EDJ-KQ61712 | Human | 2263 | Details Get a Quote |
| FGFR2 Overexpression SW620 Stable Cell Line | EDC01673 | Human | 2263 | Details Get a Quote |
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