FGFR1 Gene (Fibroblast Growth Factor Receptor 1): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of FGFR1, including genomic context, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | FGFR1 |
|---|---|
| Full Name | Fibroblast growth factor receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 8p11.23 |
| NCBI Gene ID | 2260 ncbi.nlm.nih.gov/gene/2260 |
| Ensembl ID | ENSG00000077782 |
| UniProt ID | P11362 |
| OMIM ID | 136350 |
| HGNC ID | 3688 |
| Aliases | BFGFR, CEK, FGFBR, FLT2, HBGFR, KAL2, N-SAM, bFGF-R-1, CD331, FGFR-1, FLT-2, H2, H4, H5 |
Description
FGFR1 encodes the fibroblast growth factor receptor 1, a transmembrane receptor tyrosine kinase that binds fibroblast growth factors (FGFs) and mediates signaling pathways involved in cell proliferation, differentiation, migration, and survival. It plays critical roles in embryonic development, tissue repair, and angiogenesis. Mutations and dysregulation of FGFR1 are associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pfeiffer syndrome | Gain-of-function mutations in FGFR1 lead to constitutive activation of the receptor, causing abnormal skeletal development. | OMIM, ClinVar |
| Osteoglophonic dysplasia | Missense mutations in FGFR1 result in constitutive activation, affecting bone growth. | OMIM, ClinVar |
| Kallmann syndrome | Loss-of-function mutations in FGFR1 impair neuronal migration and gonadotropin-releasing hormone neuron development. | OMIM, ClinVar |
| Hartsfield syndrome | Mutations in FGFR1 cause syndromic holoprosencephaly with ectrodactyly, likely due to disrupted FGFR1 signaling. | OMIM, ClinVar |
| Lung cancer | FGFR1 amplification and overexpression lead to aberrant signaling promoting tumor growth. | COSMIC, ClinVar |
| Breast cancer | FGFR1 amplification is associated with poor prognosis and endocrine therapy resistance. | COSMIC, ClinVar |
| Glioblastoma | FGFR1 mutations and fusions (e.g., FGFR1-TACC1) drive tumorigenesis via constitutive activation. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Lung | 3.1 | Low |
| Liver | 1.8 | Low |
| Kidney | 4.5 | Low |
| Breast | 2.3 | Low |
| Ovary | 3.9 | Low |
| Testis | 6.7 | Medium |
| Thyroid | 4.0 | Low |
| Adipose tissue | 2.0 | Low |
| Skin | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 4.2 | Moderate expression |
| MCF7 (breast cancer) | 6.8 | High expression |
| U87MG (glioblastoma) | 5.5 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 2.1 | Low expression |
| K562 (chronic myelogenous leukemia) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| N546K | Missense | Rare | Gain-of-function; constitutive activation |
| K656E | Missense | Rare | Gain-of-function; constitutive activation |
| P252R | Missense | Rare | Gain-of-function; associated with Pfeiffer syndrome |
| R622C | Missense | Rare | Gain-of-function; associated with Pfeiffer syndrome |
| G703C | Missense | Rare | Gain-of-function; associated with osteoglophonic dysplasia |
| FGFR1-TACC1 fusion | Fusion | Rare | Constitutive activation; oncogenic in glioblastoma |
| Amplification | Copy number gain | Variable (e.g., 10-20% in lung squamous cell carcinoma) | Overexpression leading to aberrant signaling |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FGFR1 are rare but can cause Kallmann syndrome and Hartsfield syndrome, impairing receptor signaling and leading to developmental defects.
Gain of Function (GOF)
Gain-of-function mutations (e.g., N546K, K656E) result in constitutive receptor activation, driving oncogenesis and skeletal disorders.
Dominant Negative (DN)
Dominant-negative effects have been suggested for some FGFR1 mutations, but evidence is limited; most pathogenic mutations are gain-of-function.
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 | • angiogenesis |
| • MAPK cascade | • PI3K-Akt signaling pathway |
| • Ras protein signal transduction | • positive regulation of cell migration |
Pathways
• FGF signaling pathway
• MAPK/ERK signaling pathway
• PI3K-Akt signaling pathway
• PLC-gamma signaling pathway
• Ras signaling pathway
• JAK-STAT signaling pathway
• Regulation of angiogenesis
• Embryonic development
Protein Summary
FGFR1 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, FGFR1 dimerizes and autophosphorylates, activating downstream signaling cascades such as RAS-MAPK, PI3K-AKT, and PLCγ. It is essential for development and tissue homeostasis, and its dysregulation is implicated in cancer and congenital disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGFR1OP2 Knockout HEK293 Cell Line | EDJ-KQ8418 | Human | 26127 | Details Get a Quote |
| FGFR1 Knockout HEK293 Cell Line | EDJ-KQ17681 | Human | 2260 | Details Get a Quote |
| FGFR1 Knockout A-549 Cell Line | EDJ-KQ19175 | Human | 2260 | Details Get a Quote |
| FGFR1 Knockout HCT 116 Cell Line | EDJ-KQ19176 | Human | 2260 | Details Get a Quote |
| FGFR1 Knockout HeLa Cell Line | EDJ-KQ19177 | Human | 2260 | Details Get a Quote |
| FGFR1OP2 Knockout A-549 Cell Line | EDJ-KQ34506 | Human | 26127 | Details Get a Quote |
| FGFR1OP2 Knockout HCT 116 Cell Line | EDJ-KQ34507 | Human | 26127 | Details Get a Quote |
| FGFR1OP2 Knockout HeLa Cell Line | EDJ-KQ34508 | Human | 26127 | Details Get a Quote |
| Fgfr1 Knockout H9c2(2-1) Cell Line | EDJ-KZ252 | Rat | 2260 | Details Get a Quote |
| FGFR1 Knockout HGC-27 Cell Line | EDJ-KZ253 | Human | 2260 | Details Get a Quote |
| FGFR1 (p.K502N) Point Mutation in HAP1 Cell Line | EDC03488 | Human | 2260 | Details Get a Quote |
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