Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB.
Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation (By similarity)
Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:10821861, PubMed:1309590, PubMed:17086194).
Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23.
Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains). Interacts with FRS2. Interacts with RPS6KA1.
Interacts (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL (PubMed:17086194). Interacts with SHB (via SH2 domain) (PubMed:12181353).
Interacts with GRB10 (By similarity). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (By similarity). Interacts with SOX2 and SOX3 (PubMed:17728342).
Interacts with FLRT1, FLRT2 and FLRT3 (PubMed:16872596). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (By similarity)
Widely expressed
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains (By similarity)
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to FGFR1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 8
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT04919642 | Cholangiocarcinoma, FGFR2 Fusion, FGFR2 Gene Mutation, FGFR1 Alteration, FGFR3 Alteration | Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma | PHASE2 | COMPLETED |
| NCT06551896 | Urothelial Carcinoma, Breast Neoplasms, Lung Cancer, Gastric Cancer, Soft Tissue Sarcoma, Other Carcinoma | Pemigatinib and Immune Checkpoint Inhibitor Treated FGFR1/2/3 Alteration Advanced Solid Tumor | PHASE2 | NOT_YET_RECRUITING |
| NCT01791985 | Breast Cancer | AZD4547 & Anastrozole or Letrozole (NSAIs) in ER+ Breast Cancer Patients Who Have Progressed on NSAIs (RADICAL) | PHASE1, PHASE2 | COMPLETED |
| NCT01283945 | Solid Tumors | Study of Oral Lucitanib (E-3810), a Dual VEGFR-FGFR Tyrosine Kinase Inhibitor, in Patients With Solid Tumors | PHASE1, PHASE2 | COMPLETED |
| NCT04125693 | Cancer | Roll-over Study to Continue Treatment With the Investigational Drug Rogaratinib and to Further Test Its Safety | PHASE2 | COMPLETED |
| NCT02202746 | Breast Cancer, Metastatic Breast Cancer, MBC, HER2 Positive, HER2, Estrogen Receptor Positive, ER, Triple Negative | A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer | PHASE2 | TERMINATED |
| NCT01948297 | Solid Tumours | Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations | PHASE1 | TERMINATED |
| NCT03834220 | Solid Tumor | Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial) | PHASE2 | TERMINATED |
| NCT07292168 | Renal Cell Carcinoma Metastatic, Prostate Cancer Metastatic, Non-small Cell Lung Cancer Metastatic, Breast Cancer Metastatic, Head & Neck Cancer | A Phase 1b/2 Study of the Safety and Efficacy of the Monoclonal Antibody OM-RCA-01 in Patients With Metastatic Tumors Expressing Fibroblast Growth Factor Receptor 1 | PHASE1, PHASE2 | RECRUITING |
| NCT05145010 | Achondroplasia | Extension Study of Infigratinib in Children With Achondroplasia (ACH) | PHASE2 | ENROLLING_BY_INVITATION |