FGFR1

Summary

FGFR1 (fibroblast growth factor receptor 1, HGNC:3688) is a protein-coding gene on chromosome 8p11.23, encoding Fibroblast growth factor receptor 1 (P11362). 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. In precision oncology, ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation confers sensitivity to Pemigatinib in Myeloid Neoplasm (CIViC Level A); 36 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 11.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

Source: NCBI Gene 2260 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Pfeiffer syndrome type 1 (Definitive, ClinGen) — +15 more curated relationships
• GWAS associations: 61
• Clinical variants (ClinVar): 1,542 total — 158 pathogenic, 96 likely-pathogenic
• Phenotypes (HPO): 408
• Druggable target: yes — 93 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 37 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_023110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3688
Approved symbol	FGFR1
Name	fibroblast growth factor receptor 1
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	H2, H3, H4, H5, CEK, FLG, BFGFR, N-SAM, CD331
Ensembl gene	ENSG00000077782
Ensembl biotype	protein_coding
OMIM	136350
Entrez	2260

Gene structure

Transcript identifiers

Ensembl transcripts: 73 — 38 protein_coding, 21 retained_intron, 8 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined

ENST00000326324, ENST00000335922, ENST00000341462, ENST00000356207, ENST00000397090, ENST00000397091, ENST00000397103, ENST00000397108, ENST00000397113, ENST00000413133, ENST00000425967, ENST00000434187, ENST00000440174, ENST00000447712, ENST00000464163, ENST00000466021, ENST00000470826, ENST00000474970, ENST00000475621, ENST00000480571, ENST00000484370, ENST00000487647, ENST00000496296, ENST00000496629, ENST00000524528, ENST00000525001, ENST00000526570, ENST00000526688, ENST00000526742, ENST00000527114, ENST00000527203, ENST00000527745, ENST00000529552, ENST00000530568, ENST00000530701, ENST00000531196, ENST00000532386, ENST00000532791, ENST00000533301, ENST00000533619, ENST00000533668, ENST00000619564, ENST00000649678, ENST00000674189, ENST00000674217, ENST00000674235, ENST00000674380, ENST00000674474, ENST00000682398, ENST00000682770, ENST00000683132, ENST00000683276, ENST00000683765, ENST00000683795, ENST00000683815, ENST00000683948, ENST00000684654, ENST00000703405, ENST00000857933, ENST00000857934, ENST00000857935, ENST00000857936, ENST00000857937, ENST00000857938, ENST00000857939, ENST00000857940, ENST00000934569, ENST00000934570, ENST00000934571, ENST00000934572, ENST00000934573, ENST00000965843, ENST00000965844

RefSeq mRNA: 14 — MANE Select: NM_023110 NM_001174063, NM_001174064, NM_001174065, NM_001174066, NM_001174067, NM_001354367, NM_001354368, NM_001354369, NM_001354370, NM_001410922, NM_015850, NM_023105, NM_023106, NM_023110

CCDS: CCDS43730, CCDS43731, CCDS43732, CCDS55221, CCDS55222, CCDS6107, CCDS94283, CCDS94284, CCDS94285

Canonical transcript exons

ENST00000447712 — 18 exons

Exon	Start	End
ENSE00001316315	38429682	38429948
ENSE00001630314	38411143	38413804
ENSE00001911865	38467981	38468635
ENSE00003489763	38418228	38418373
ENSE00003501167	38424509	38424699
ENSE00003510418	38421797	38421941
ENSE00003523010	38415870	38416060
ENSE00003528389	38419533	38419735
ENSE00003551643	38428346	38428435
ENSE00003576378	38414779	38414901
ENSE00003597475	38414559	38414629
ENSE00003610788	38457356	38457534
ENSE00003611337	38413918	38414023
ENSE00003614250	38427921	38428093
ENSE00003614946	38417870	38417991
ENSE00003644071	38417306	38417416
ENSE00003680911	38414152	38414289
ENSE00003683948	38426122	38426245

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.3926 / max 1147.7880, expressed in 1712 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92760	48.8415	1699
92759	5.5237	1443
92756	1.7125	788
92758	1.4635	763
92757	0.4747	268
92754	0.2544	121
92755	0.1222	57

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.95	gold quality
stromal cell of endometrium	CL:0002255	98.88	gold quality
calcaneal tendon	UBERON:0003701	98.84	gold quality
right ovary	UBERON:0002118	98.59	gold quality
paraflocculus	UBERON:0005351	98.54	gold quality
left ovary	UBERON:0002119	98.49	gold quality
right coronary artery	UBERON:0001625	98.47	gold quality
left uterine tube	UBERON:0001303	98.44	gold quality
cerebellar hemisphere	UBERON:0002245	98.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.38	gold quality
cerebellar cortex	UBERON:0002129	98.37	gold quality
cerebellum	UBERON:0002037	98.30	gold quality
descending thoracic aorta	UBERON:0002345	98.29	gold quality
body of pancreas	UBERON:0001150	98.25	gold quality
ascending aorta	UBERON:0001496	98.23	gold quality
thoracic aorta	UBERON:0001515	98.22	gold quality
aorta	UBERON:0000947	98.17	gold quality
popliteal artery	UBERON:0002250	98.16	gold quality
tibial artery	UBERON:0007610	98.15	gold quality
gall bladder	UBERON:0002110	98.11	gold quality
mucosa of stomach	UBERON:0001199	98.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.06	gold quality
saphenous vein	UBERON:0007318	98.05	gold quality
lower esophagus	UBERON:0013473	98.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.02	gold quality
colonic epithelium	UBERON:0000397	97.94	gold quality
omental fat pad	UBERON:0010414	97.90	gold quality
coronary artery	UBERON:0001621	97.89	gold quality
peritoneum	UBERON:0002358	97.89	gold quality
tibial nerve	UBERON:0001323	97.83	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	102.45
E-MTAB-5061	yes	16.38
E-CURD-112	yes	16.29
E-GEOD-93593	yes	15.18
E-GEOD-81608	yes	8.20
E-MTAB-8271	yes	7.09
E-MTAB-9067	yes	6.40
E-ENAD-27	yes	5.05
E-GEOD-83139	yes	4.35
E-MTAB-10018	no	352.76
E-HCAD-31	no	4.92
E-MTAB-9801	no	2.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, APLN, ARNT, ASCL2, ASCL4, ATF1, ATOH1, ATOH8, CEBPB, DLX2, DNMT1, DNMT3B, E2F1, E2F4, EZH2, FGF2, FOXO3, GATA3, GATA4, GLI2, HINFP, HOXD4, ID1, ID2, IRF1, IRF2, IRF3, IRF8, KAT7, KAT8, KDM2A, KDM5A, KDM5B, KDM5C, KLF10, KLF11, KLF14, KLF9, KMT2A

miRNA regulators (miRDB)

121 targeting FGFR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 11.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• vitronectin increased the presence of all four growth factor receptors and most notably, VEGFR-1; in contrast, fibrin decreased all four receptors, especially FGFR-1 and FGFR-2 (PMID:11693202)
• In the fusion of the FGFR1 and BCR genes in myeloproliferative disorder, it is likely that the dimerization properties of BCR lead to aberrant FGFR1 signaling and neoplastic transformation. (PMID:11746971)
• distribution in normal endocrine cells and related tumors of the gastroenteropancreatic system; immunoreactive in rare duodenal endocrine cells and in pancreatic A cells (PMID:11759058)
• REVIEW; The 8p11 myeloproliferative syndrome is a distinct clinical entity caused by constitutive activation of FGFR1. (PMID:11919391)
• overexpressed in acute myeloid luekemia while translocations associated with this gene are absent, and more frequently in patients with CD56 immunophenoytpe (PMID:12031912)
• Inhibiting expression of bFGF or FGFR-1 in only the melanoma cells is as effective in blocking tumor growth as simultaneously inhibiting bFGF or FGFR-1 synthesis in the melanoma cells and the melanoma cell-interspersing vasculature. (PMID:12080186)
• CD56 molecules on NK cells interact with fibroblast growth factor receptor 1 on Jurkat T cells to trigger IL-2 production. (PMID:12121226)
• Review of FGFR1 isoforms and structure-activity analysis [review] (PMID:12141425)
• Differences in spatial patterns of FGFR expression in normal skin may generate functional diversity in response to FGFs, and in wounded skin FGFs may function in wound healing via induced FGFRs. (PMID:12373339)
• Our results suggest an autocrine role of the FGF-FGFR-1 system in the pathogenesis of COPD-associated vascular remodeling. (PMID:12397010)
• Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells. (PMID:12411316)
• Recombinant FGFR1 was expressed on the surface of Sf9 insect cells. The peptide ValTyrMetSerProPhe can specifically bind to the hydrophobic surface of FGFR1. (PMID:12440521)
• alternatively spliced FGFR-1 isoforms induce differential signal transduction pathways (PMID:12573278)
• ZNF198/fibroblast growth factor receptor-1 has signaling function comparable with interleukin-6 cytokine receptors. (PMID:12594223)
• FGFR1 tyrosine phosphorylation is inhibited by sef protein (PMID:12604616)
• cAMP-induced nuclear accumulation of FGFR1 provides a signal that triggers molecular events leading to neuronal differentiation of neuronal progenitor cells (PMID:12614330)
• FGFR1 has a role in autosomal dominant Kallmann syndrome (PMID:12627230)
• expression system is involved in angiogenesis in inflamed synovial tissue in the temporomandibular joint (PMID:12651930)
• TSH stimulates FGFR1 but not FGF-2 expression and PKC activation stimulates FGF-2 synthesis and secretion, and TSH synergizes with PKC activators so increases in FGFR1 or FGF-2 or in both may contribute to goitrogenesis. (PMID:12746216)
• Results describe a direct interaction between neural cell adhesion molecule (fibronectin type III [F3] modules 1 and 2) and fibroblast growth factor receptor R1 (Ig modules 2 and 3) by surface plasmon resonance analysis. (PMID:12791257)
• HFGFR1 was expressed primarily in the ventricular zone embryologically (PMID:12794748)
• Tyrosine 463 is phosphorylated and able to transduce signals in response to FGF-2 treatment alone. Furthermore, FGFR-1 dimerization/kinase activation is stabilized by heparin. (PMID:12799194)
• involvement of a nuclear matrix bound FGFR1 in transcriptional and RNA processing events in the cell nucleus (PMID:14587039)
• Here we show that the TCR and fibroblast growth factor receptors co-localize during combined stimulation [which] synergistically enhances the activation of nuclear factors of activated T cells. (PMID:14636241)
• two novel intragenic FGFR1 mutations in two sporadic male cases in Kallmann syndrome (PMID:15001591)
• The weak binding affinity of the fibroblast growth factor receptor (FGFR) 1 interaction with heparin suggests that in this model, FGFR and heparan sulfate proteoglycan are unbound in the absence of FGF ligand on the cell surface. (PMID:15096041)
• Results suggest that active fibroblast growth factor receptor 1 kinase regulates the functions of nuclear 90-kDa ribosomal S6 kinase. (PMID:15117958)
• Although FGFR-1 dimerization achieved by fgfr-2 injection led to highly differentiated and smaller bladder tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF. (PMID:15273729)
• fibrinogen binding of FGF-2 enhances EC proliferation through the coordinated effects of colocalized alpha(v)beta(3) and FGFR1 (PMID:15297314)
• insulin receptor substrate-4 and ShcA have roles in signaling by the fibroblast growth factor receptor (PMID:15316024)
• conjoint endocytosis and trafficking is a novel mechanism for the coregulation of E-cadherin and FGFR1 during cell signaling and morphogenesis (PMID:15509650)
• The reciprocal relationship in gene expression between FGFR1 and FGFR3 in colorectal tissue plays an important role in the progression of the carcinomas to malignancy. (PMID:15558020)
• Recruitment of SRC to FRS2 leads to activation of signal attenuation pathways. (PMID:15564375)
• the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and a loss of function mutation in the FGFR1 gene causing delayed puberty. (PMID:15613419)
• In ‘undifferentiated’ neurospheres of embryonic brain and spinal cord, transcripts from FGFR1 and FGFR2 were consistently detected. (PMID:15618886)
• Fibroblast growth factor trophic signaling to differentiated neurons could involve the release of astrocytic basic FGF acting on neuronal FGFR1 expression. (PMID:15680705)
• FGFR-1 is expressed in early hematopoietic/endothelial precursor cells, as well as in a subpool of endothelial cells in tumor vessels, and that it is critical for hematopoietic but not for vascular development (PMID:15774903)
• When used individually, FGFR1 partially prevented goiter and sVEGFR1 partially reduced vascular volume. (PMID:15817662)
• The interaction of FGFR1 with CREB binding protein allows activation of gene transcription and may play a role in cell differentiation. (PMID:15929978)
• involvement of a nuclear matrix bound FGFR1 in transcriptional and RNA processing events in the cell nucleus (PMID:15955231)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgfr1a	ENSDARG00000011027
danio_rerio	fgfr1b	ENSDARG00000011190
danio_rerio	fgfr1bl	ENSDARG00000104015
mus_musculus	Fgfr1	ENSMUSG00000031565
rattus_norvegicus	Fgfr1	ENSRNOG00000016050

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Fibroblast growth factor receptor 1 — P11362 (reviewed: P11362)

Alternative names: Basic fibroblast growth factor receptor 1, Fms-like tyrosine kinase 2, N-sam, Proto-oncogene c-Fgr

All UniProt accessions (21): P11362, A0A0S2Z3Q6, A0A0S2Z3T4, A0A0S2Z3T9, A0A3B3ISD1, A0A6I8PRY1, A0A6I8PTV4, A0A804HIF1, A0A8I3B1S4, A0A994J419, B5A958, C9J1L5, C9J205, E7EU09, E9PKF2, E9PKV7, E9PKX3, E9PN14, E9PNM3, E9PQ40, H0YE20

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. 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). 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. Interacts with SHB (via SH2 domain). Interacts with GRB10. Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2. Interacts with SOX2 and SOX3. Interacts with FLRT1, FLRT2 and FLRT3. Found in a ternary complex with FGF1 and ITGAV:ITGB3.

Subcellular location. Cell membrane. Nucleus. Cytoplasm. Cytosol. Cytoplasmic vesicle.

Tissue specificity. Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.

Post-translational modifications. Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation. Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1. N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.

Disease relevance. Pfeiffer syndrome (PS) [MIM:101600] A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3). The disease is caused by variants affecting the gene represented in this entry. Hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950] A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3. Osteoglophonic dysplasia (OGD) [MIM:166250] Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Hartsfield syndrome (HRTFDS) [MIM:615465] A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound intellectual disability is also present. Multiple other congenital anomalies usually occur. The disease is caused by variants affecting the gene represented in this entry. Trigonocephaly 1 (TRIGNO1) [MIM:190440] A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head. The disease is caused by variants affecting the gene represented in this entry. Chromosomal aberrations involving FGFR1 are a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(8;13)(p11;q12) with ZMYM2. Translocation t(6;8)(q27;p11) with CEP43. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. Translocation t(8;9)(p12;q33) with CNTRL. Translocation t(2;8)(q12;p11) with RANBP2. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity. Encephalocraniocutaneous lipomatosis (ECCL) [MIM:613001] A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present. The disease is caused by variants affecting the gene represented in this entry. Jackson-Weiss syndrome (JWS) [MIM:123150] An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues. Inhibited by ARQ 069; this compound maintains the kinase in an inactive conformation and inhibits autophosphorylation. Inhibited by PD173074.

Domain organisation. 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.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.

Isoforms (21)

UniProt ID	Names	Canonical?
P11362-1	1, Alpha A1, IV	yes
P11362-8	2, Alpha A2
P11362-17	3, Alpha A3
P11362-2	4, Alpha B1
P11362-9	5, Alpha B2
P11362-3	6, Beta A1, II, H2
P11362-10	7, Beta A2
P11362-4	8, Beta B1
P11362-11	9, Beta B2
P11362-5	10, Gamma A1
P11362-12	11, Gamma A2
P11362-6	12, Gamma B1
P11362-13	13, Gamma B2
P11362-7	14, A, III
P11362-14	15, I, H3
P11362-15	16, V
P11362-16	17, H4
P11362-18	18, H5
P11362-19	19
P11362-20	20
P11362-21	21

RefSeq proteins (14): NP_001167534, NP_001167535, NP_001167536, NP_001167537, NP_001167538, NP_001341296, NP_001341297, NP_001341298, NP_001341299, NP_001397851, NP_056934, NP_075593, NP_075594, NP_075598* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016248	FGF_rcpt_fam	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR028174	FGF_rcpt_1	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00047, PF07679, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (238 total): sequence variant 92, strand 44, helix 18, splice variant 17, sequence conflict 11, mutagenesis site 8, glycosylation site 8, modified residue 7, binding site 6, turn 4, site 4, domain 4, region of interest 3, compositionally biased region 3, disulfide bond 3, topological domain 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

83 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5EW8	X-RAY DIFFRACTION	1.63
4WUN	X-RAY DIFFRACTION	1.65
9U7G	X-RAY DIFFRACTION	1.66
7OZB	X-RAY DIFFRACTION	1.71
8XZ7	X-RAY DIFFRACTION	1.75
9UHI	X-RAY DIFFRACTION	1.76
9VLJ	X-RAY DIFFRACTION	1.81
7OZD	X-RAY DIFFRACTION	1.82
7OZF	X-RAY DIFFRACTION	1.82
9UHC	X-RAY DIFFRACTION	1.88
5O49	X-RAY DIFFRACTION	1.91
3DPK	X-RAY DIFFRACTION	1.95
5AM7	X-RAY DIFFRACTION	1.96
4UWC	X-RAY DIFFRACTION	1.96
5AM6	X-RAY DIFFRACTION	1.96
8JMZ	X-RAY DIFFRACTION	1.99
6ITJ	X-RAY DIFFRACTION	1.99
1FGK	X-RAY DIFFRACTION	2
4ZSA	X-RAY DIFFRACTION	2
6C1B	X-RAY DIFFRACTION	2
6MZQ	X-RAY DIFFRACTION	2
3RHX	X-RAY DIFFRACTION	2.01
5O4A	X-RAY DIFFRACTION	2.01
4F64	X-RAY DIFFRACTION	2.05
3C4F	X-RAY DIFFRACTION	2.07
5A4C	X-RAY DIFFRACTION	2.09
3KRJ	X-RAY DIFFRACTION	2.1
4V04	X-RAY DIFFRACTION	2.12
6C19	X-RAY DIFFRACTION	2.12
5B7V	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11362-F1	74.30	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (5): 623 (proton acceptor); 428–429 (breakpoint for translocation to form cep43-fgfr1 or fgfr1-cep43 fusion proteins); 428–429 (breakpoint for translocation to form cntrl-fgfr1 or fgfr1-cntrl fusion proteins); 428–429 (breakpoint for translocation to form fgfr1op2-fgfr1); 766 (mediates interaction with plcg1 and shb)

Ligand- & substrate-binding residues (6): 484–490; 514; 562–564; 568; 627; 641

Post-translational modifications (7): 463, 583, 585, 653, 654, 730, 766

Disulfide bonds (3): 55–101, 178–230, 277–341

Glycosylation sites (8): 77, 117, 227, 240, 264, 296, 317, 330

Mutagenesis-validated functional residues (8):

Position	Phenotype
514	loss of kinase activity.
577	strongly reduced autophosphorylation in response to fgf signaling. no effect on in vitro kinase activity.
609	abolishes interaction with plcg1.
623	loss of kinase activity.
653	no effect on kinase activity. loss of autophosphorylation and kinase activity; when associated with f-654.
654	reduced kinase activity. loss of autophosphorylation and kinase activity; when associated with f-653.
755	abolishes interaction with plcg1.
766	abolishes interaction with plcg1 and shb. decreases phosphorylation of frs2, activation of ras and map kinase signaling

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-1839122	Signaling by activated point mutants of FGFR1
R-HSA-5655302	Signaling by FGFR1 in disease
R-HSA-8853336	Signaling by plasma membrane FGFR1 fusions
R-HSA-9758919	Epithelial-Mesenchymal Transition (EMT) during gastrulation
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1839120	Signaling by FGFR1 amplification mutants
R-HSA-190370	FGFR1b ligand binding and activation
R-HSA-190373	FGFR1c ligand binding and activation
R-HSA-190374	FGFR1c and Klotho ligand binding and activation
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-445144	Signal transduction by L1
R-HSA-5654219	Phospholipase C-mediated cascade: FGFR1
R-HSA-5654687	Downstream signaling of activated FGFR1
R-HSA-5654688	SHC-mediated cascade:FGFR1
R-HSA-5654689	PI-3K cascade:FGFR1
R-HSA-5654693	FRS-mediated FGFR1 signaling
R-HSA-5654726	Negative regulation of FGFR1 signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 1469 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_CARTILAGE_DEVELOPMENT

GO Biological Process (86): negative regulation of transcription by RNA polymerase II (GO:0000122), MAPK cascade (GO:0000165), skeletal system development (GO:0001501), angiogenesis (GO:0001525), ureteric bud development (GO:0001657), in utero embryonic development (GO:0001701), organ induction (GO:0001759), neuron migration (GO:0001764), epithelial to mesenchymal transition (GO:0001837), positive regulation of mesenchymal cell proliferation (GO:0002053), chondrocyte differentiation (GO:0002062), protein phosphorylation (GO:0006468), sensory perception of sound (GO:0007605), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), mesenchymal cell proliferation (GO:0010463), gene expression (GO:0010467), positive regulation of phospholipase activity (GO:0010518), regulation of phosphate transport (GO:0010966), positive regulation of neuron projection development (GO:0010976), cell migration (GO:0016477), peptidyl-tyrosine phosphorylation (GO:0018108), ventricular zone neuroblast division (GO:0021847), cell projection assembly (GO:0030031), embryonic limb morphogenesis (GO:0030326), midbrain development (GO:0030901), neuron projection development (GO:0031175), fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development (GO:0035607), inner ear morphogenesis (GO:0042472), outer ear morphogenesis (GO:0042473), middle ear morphogenesis (GO:0042474), chordate embryonic development (GO:0043009), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), positive regulation of blood vessel endothelial cell migration (GO:0043536), cellular response to fibroblast growth factor stimulus (GO:0044344), regulation of cell differentiation (GO:0045595), positive regulation of cell differentiation (GO:0045597), positive regulation of neuron differentiation (GO:0045666), protein autophosphorylation (GO:0046777)

GO Molecular Function (15): protein tyrosine kinase activity (GO:0004713), fibroblast growth factor receptor activity (GO:0005007), ATP binding (GO:0005524), heparin binding (GO:0008201), fibroblast growth factor binding (GO:0017134), SH2 domain binding (GO:0042169), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), receptor-receptor interaction (GO:0090722), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane receptor protein tyrosine kinase activity (GO:0004714), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): extracellular region (GO:0005576), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), signaling receptor complex (GO:0043235), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Downstream signaling of activated FGFR1	4
FGFR1 mutant receptor activation	3
FGFR1 ligand binding and activation	3
Gastrulation	2
Signaling by FGFR1	2
Signaling by FGFR in disease	1
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Axon guidance	1
L1CAM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell population proliferation	2
cytoplasm	2
synapse	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
intracellular signaling cassette	1
system development	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
mesonephric tubule development	1
chordate embryonic development	1
regulation of animal organ formation	1
specification of animal organ identity	1
developmental induction	1
positive regulation of animal organ morphogenesis	1
cell migration	1
generation of neurons	1
mesenchymal cell differentiation	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
cell differentiation	1
cartilage development	1
phosphorylation	1
protein modification process	1
sensory perception of mechanical stimulus	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
macromolecule biosynthetic process	1
glycerophospholipase activity	1
regulation of phospholipase activity	1
positive regulation of lipase activity	1
phosphate ion transport	1
regulation of transport	1
regulation of neuron projection development	1
neuron projection development	1

Protein interactions and networks

STRING

4013 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGFR1	FGF8	P55075	999
FGFR1	FGF4	P08620	998
FGFR1	FGF2	P09038	998
FGFR1	FGF9	P31371	998
FGFR1	FGF1	P05230	998
FGFR1	FGF13	Q92913	998
FGFR1	FGF6	P10767	997
FGFR1	FGF23	Q9GZV9	997
FGFR1	KLB	Q86Z14	997
FGFR1	FGF10	O15520	997
FGFR1	FGF7	P21781	997
FGFR1	FGF5	P12034	997
FGFR1	FGF3	P11487	997
FGFR1	FGF17	O60258	997
FGFR1	KL	Q9UEF7	997

IntAct

232 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
FGF2	FGFR1	psi-mi:“MI:0407”(direct interaction)	0.910
FGFR1	FGF2	psi-mi:“MI:0407”(direct interaction)	0.910
FGFR1	PLCG1	psi-mi:“MI:0217”(phosphorylation reaction)	0.900
PLCG1	FGFR1	psi-mi:“MI:0407”(direct interaction)	0.900
FGFR1	PLCG1	psi-mi:“MI:0407”(direct interaction)	0.900
PLCG1	FGFR1	psi-mi:“MI:2364”(proximity)	0.900
FGFR1	FGF1	psi-mi:“MI:0407”(direct interaction)	0.840
FGF1	FGFR1	psi-mi:“MI:0407”(direct interaction)	0.840
FGFR1	FGF1	psi-mi:“MI:2364”(proximity)	0.840
FGF23	Kl	psi-mi:“MI:0915”(physical association)	0.730
HSP90AB1	FGFR1	psi-mi:“MI:0915”(physical association)	0.670
FGFR1	NEDD4	psi-mi:“MI:0407”(direct interaction)	0.670
NEDD4	FGFR1	psi-mi:“MI:0407”(direct interaction)	0.670

BioGRID (1448): NEDD4 (Affinity Capture-Western), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM20, F1LW30, O73875, O73878, P00545, P07333, P11362, P13369, P16092, P18460, P21709, P21803, P21804, P22182, P22455, P22607, P29317, P54755, P54756, P54757, P54759, P54761, P55144, P55146, P57097, Q03142, Q04589, Q06418, Q06806, Q12866, Q15375, Q1KL86, Q498D6, Q60629, Q60750, Q60805, Q61772, Q61851, Q6UXZ4, Q8K1S2

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

64 interactions.

A	Effect	B	Mechanism
MAPK14	down-regulates	FGFR1	phosphorylation
FGFR1	up-regulates	LDHA	phosphorylation
BGJ-398	down-regulates	FGFR1	“chemical inhibition”
“Brivanib alaninate”	down-regulates	FGFR1	“chemical inhibition”
FGFR1	up-regulates	PDK1	phosphorylation
MAPK1	down-regulates	FGFR1	phosphorylation
MAPK3	down-regulates	FGFR1	phosphorylation
PRKCE	up-regulates	FGFR1	phosphorylation
PD173074	down-regulates	FGFR1	“chemical inhibition”
orantinib	down-regulates	FGFR1	“chemical inhibition”
FGFR1	up-regulates	MAP2K1
FGF1	“up-regulates activity”	FGFR1	binding
ERK1/2	down-regulates	FGFR1	phosphorylation
FGFR1	up-regulates	MEK1/2
pazopanib	“down-regulates activity”	FGFR1	“chemical inhibition”
regorafenib	“down-regulates activity”	FGFR1	“chemical inhibition”
ponatinib	“down-regulates activity”	FGFR1	“chemical inhibition”
FGFR1	“down-regulates activity”	“Non-structural protein 2”	“chemical inhibition”
FGFR1	“up-regulates activity”	ACAT1	phosphorylation
Gbeta	down-regulates	FGFR1	phosphorylation
FGFR1	“up-regulates activity”	AMOTL2	phosphorylation
RPS6KA3	“down-regulates quantity”	FGFR1	phosphorylation
DUSP26	“down-regulates activity”	FGFR1	dephosphorylation
FGFR1	“up-regulates activity”	PDPK1	phosphorylation
FGFR1	“up-regulates activity”	PGAM1	phosphorylation
EPHA4	“up-regulates activity”	FGFR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Phospholipase C-mediated cascade; FGFR4	10	62.4×	1e-14
PI-3K cascade:FGFR4	11	51.5×	9e-15
FGFR1c ligand binding and activation	8	49.9×	3e-11
Phospholipase C-mediated cascade; FGFR2	9	46.8×	4e-12
PI-3K cascade:FGFR3	9	46.8×	4e-12
FRS-mediated FGFR4 signaling	11	44.8×	3e-14
SHC-mediated cascade:FGFR4	10	44.6×	5e-13
Activated point mutants of FGFR2	8	44.0×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
fibroblast growth factor receptor signaling pathway	15	28.6×	4e-15
positive regulation of stem cell proliferation	6	21.1×	6e-05
positive regulation of cell division	7	15.7×	6e-05
positive regulation of blood vessel endothelial cell migration	5	13.1×	4e-03
neurogenesis	9	12.5×	1e-05
stem cell proliferation	6	12.5×	1e-03
cellular response to UV	6	11.8×	1e-03
epidermal growth factor receptor signaling pathway	7	11.6×	3e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

FGFR1 is a member of the Fibroblast Growth Factor family, comprising of 4 receptors and 18 Ligands. FGFR1 signalling downstream functions mainly via PI3K and MAPK pathways (Turner et. al.). Several ways of involvement of FGFR1 in cancer have been proposed: auto- and paracrine activation, amplification and overexpression (Marshall et. al, Weiss et. al., Cheng et. al.). Especially amplification of FGFR1 in lung cancer is an emerging treatment target with clinical studies currently ongoing (e.g. NCT01004224). However, FGFR1 amplification does not always correlate with protein expression and predictive biomarkers still remain to be defined in clinic (von Mässenhausen et. al.). Mutation of FGFR1 seems to be less common, but has been described in glioblastoma, pilocytic astrocytomas and Ewing’s sarcoma (Rand et. al., Jones et. al., Agelopoulos et. al.).

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — BLCA, GBM, OVT, PANCREAS, PAST, PGNG, WDTC.

Clinical variants and AI predictions

ClinVar

1542 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	158
Likely pathogenic	96
Uncertain significance	618
Likely benign	352
Benign	86

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032025	NM_002016.2(FLG):c.5368C>T (p.Gln1790Ter)	Pathogenic
1074220	NM_023110.3(FGFR1):c.979_983del (p.His327fs)	Pathogenic
1184446	NM_023110.3(FGFR1):c.2122G>T (p.Glu708Ter)	Pathogenic
1208776	NM_023110.3(FGFR1):c.962_963del (p.Lys321fs)	Pathogenic
1212174	NM_002016.2(FLG):c.9061G>T (p.Gly3021Ter)	Pathogenic
1228379	NM_002016.2(FLG):c.5198C>G (p.Ser1733Ter)	Pathogenic
1299865	NM_002016.2(FLG):c.1378G>T (p.Glu460Ter)	Pathogenic
1325967	NM_002016.2(FLG):c.1685C>A (p.Ser562Ter)	Pathogenic
132646	NM_023110.3(FGFR1):c.790A>C (p.Asn264His)	Pathogenic
132647	NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp)	Pathogenic
132648	NM_023110.3(FGFR1):c.2084C>T (p.Thr695Ile)	Pathogenic
1338306	NM_023110.3(FGFR1):c.2223del (p.Ser742fs)	Pathogenic
1338919	NM_023110.3(FGFR1):c.2187-1G>A	Pathogenic
1341672	NM_023110.3(FGFR1):c.1855-1G>A	Pathogenic
1342082	NM_002016.2(FLG):c.482_485del (p.Arg161fs)	Pathogenic
1418780	NM_023110.3(FGFR1):c.1265dup (p.Leu423fs)	Pathogenic
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	Pathogenic
16285	NM_023110.3(FGFR1):c.499G>T (p.Ala167Ser)	Pathogenic
16286	NM_023110.3(FGFR1):c.989A>T (p.Asn330Ile)	Pathogenic
16287	NM_023110.3(FGFR1):c.1121A>G (p.Tyr374Cys)	Pathogenic
16296	NM_023110.3(FGFR1):c.1825C>T (p.Arg609Ter)	Pathogenic
16300	NM_023110.3(FGFR1):c.2164C>T (p.Pro722Ser)	Pathogenic
16301	NM_023110.3(FGFR1):c.2292G>T (p.Gln764His)	Pathogenic
16303	NM_023110.3(FGFR1):c.749G>A (p.Arg250Gln)	Pathogenic
1691654	NM_002016.2(FLG):c.9683_9684del (p.Asp3227_Ser3228insTer)	Pathogenic
1709350	NM_023110.3(FGFR1):c.1969dup (p.Thr657fs)	Pathogenic
1801171	NM_023110.3(FGFR1):c.246_247del (p.Glu84fs)	Pathogenic
1997422	NM_023110.3(FGFR1):c.111del (p.Val38fs)	Pathogenic
2011123	NM_023110.3(FGFR1):c.625del (p.Arg209fs)	Pathogenic
2029325	NM_023110.3(FGFR1):c.780del (p.Leu261fs)	Pathogenic

SpliceAI

5160 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152315313:TCTTA:T	donor_loss	1.0000
1:152315314:CTTAC:C	donor_loss	1.0000
1:152315315:TTAC:T	donor_loss	1.0000
1:152315316:TACC:T	donor_loss	1.0000
1:152315317:A:AC	donor_gain	1.0000
1:152315317:A:C	donor_loss	1.0000
1:152315317:AC:A	donor_gain	1.0000
1:152315318:C:CC	donor_gain	1.0000
1:152315318:C:CT	donor_loss	1.0000
1:152315318:CC:C	donor_gain	1.0000
1:152315318:CCTT:C	donor_gain	1.0000
1:152315473:TGAAC:T	acceptor_gain	1.0000
1:152315474:GAAC:G	acceptor_gain	1.0000
1:152315475:AAC:A	acceptor_gain	1.0000
1:152315476:AC:A	acceptor_gain	1.0000
1:152315477:CC:C	acceptor_gain	1.0000
1:152315478:C:CC	acceptor_gain	1.0000
8:38401051:G:GT	donor_gain	1.0000
8:38401051:GAA:G	donor_gain	1.0000
8:38401054:G:GG	donor_gain	1.0000
8:38402519:TTTCA:T	acceptor_loss	1.0000
8:38402520:TTCA:T	acceptor_loss	1.0000
8:38402522:CA:C	acceptor_loss	1.0000
8:38402523:A:AG	acceptor_gain	1.0000
8:38402523:AG:A	acceptor_loss	1.0000
8:38402524:G:GA	acceptor_gain	1.0000
8:38402524:GAT:G	acceptor_gain	1.0000
8:38402524:GATA:G	acceptor_gain	1.0000
8:38402642:G:GT	donor_gain	1.0000
8:38402642:GAGG:G	donor_loss	1.0000

AlphaMissense

5386 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:38413961:A:G	L750P	1.000
8:38413978:T:A	R744S	1.000
8:38413978:T:G	R744S	1.000
8:38413979:C:G	R744T	1.000
8:38414001:A:G	W737R	1.000
8:38414001:A:T	W737R	1.000
8:38414002:G:C	C736W	1.000
8:38414200:A:G	L713P	1.000
8:38414203:A:G	L712P	1.000
8:38414212:A:G	L709P	1.000
8:38414265:C:A	W691C	1.000
8:38414265:C:G	W691C	1.000
8:38414267:A:G	W691R	1.000
8:38414267:A:T	W691R	1.000
8:38414272:A:G	L689P	1.000
8:38414278:C:T	G687E	1.000
8:38414279:C:A	G687W	1.000
8:38414279:C:G	G687R	1.000
8:38414279:C:T	G687R	1.000
8:38414286:C:A	W684C	1.000
8:38414286:C:G	W684C	1.000
8:38414288:A:G	W684R	1.000
8:38414288:A:T	W684R	1.000
8:38414588:A:C	F673L	1.000
8:38414588:A:T	F673L	1.000
8:38414590:A:G	F673L	1.000
8:38414592:A:G	L672S	1.000
8:38414607:A:C	M667R	1.000
8:38414607:A:G	M667T	1.000
8:38414607:A:T	M667K	1.000

dbSNP variants (sampled 300 via entrez): RS1000049624 (8:38436981 C>A), RS1000092987 (8:38439274 G>A), RS1000101584 (8:38436658 T>C), RS1000141120 (8:38447355 A>T), RS1000191653 (8:38447584 C>T), RS1000247572 (8:38457548 A>C,G,T), RS1000249757 (8:38441299 G>A,T), RS1000274647 (8:38420215 G>A), RS1000410793 (8:38436236 A>T), RS1000478444 (8:38425547 G>A), RS1000496066 (8:38441106 C>A,T), RS1000586883 (8:38452038 A>G), RS1000635363 (8:38468419 G>A,C), RS1000705524 (8:38446391 A>T), RS1000782118 (8:38424640 G>A)

Disease associations

OMIM: gene MIM:136350 | disease phenotypes: MIM:101600, MIM:147950, MIM:123150, MIM:166250, MIM:190440, MIM:613001, MIM:615465, MIM:605803, MIM:119530, MIM:146110, MIM:212720, MIM:123100, MIM:236100, MIM:132400, MIM:614840, MIM:144110, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
Hartsfield-Bixler-Demyer syndrome	Definitive	Autosomal dominant
hypogonadotropic hypogonadism 2 with or without anosmia	Definitive	Autosomal dominant
osteoglophonic dysplasia	Definitive	Autosomal dominant
Pfeiffer syndrome	Definitive	Autosomal dominant
autosomal dominant ichthyosis vulgaris	Definitive	Semidominant
encephalocraniocutaneous lipomatosis	Definitive	Autosomal dominant
Jackson-Weiss syndrome	Strong	Autosomal dominant
Pfeiffer syndrome type 1	Strong	Autosomal dominant
ichthyosis vulgaris	Strong	Semidominant
holoprosencephaly	Supportive	Autosomal recessive
septooptic dysplasia	Supportive	Autosomal dominant
isolated trigonocephaly	Supportive	Autosomal dominant
hypogonadotropic hypogonadism	Supportive	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant
tooth agenesis	Supportive	Autosomal dominant
recessive X-linked ichthyosis	Supportive	X-linked

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Pfeiffer syndrome type 1	Definitive	AD
osteoglophonic dysplasia	Limited	AD
Hartsfield-Bixler-Demyer syndrome	Moderate	AD

Mondo (36): Pfeiffer syndrome (MONDO:0007043), hypogonadotropic hypogonadism 2 with or without anosmia (MONDO:0007844), Jackson-Weiss syndrome (MONDO:0007400), osteoglophonic dysplasia (MONDO:0008150), trigonocephaly 1 (MONDO:0008603), encephalocraniocutaneous lipomatosis (MONDO:0013074), Hartsfield-Bixler-Demyer syndrome (MONDO:0014196), ichthyosis vulgaris (MONDO:0024304), dermatitis, atopic, 2 (MONDO:0011596), hypogonadotropic hypogonadism (MONDO:0018555), orofacial cleft 1 (MONDO:0007335), amenorrhea (MONDO:0001836), pilomyxoid astrocytoma (MONDO:0016692), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), Martsolf syndrome 1 (MONDO:8000008)

Orphanet (23): Kallmann syndrome (Orphanet:478), Pfeiffer syndrome (Orphanet:710), Jackson-Weiss syndrome (Orphanet:1540), Hartsfield syndrome (Orphanet:2117), Encephalocraniocutaneous lipomatosis (Orphanet:2396), Osteoglosphonic dysplasia (Orphanet:2645), Non-syndromic metopic craniosynostosis (Orphanet:3366), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Pilomyxoid astrocytoma (Orphanet:251615), Cataract-intellectual disability-hypogonadism syndrome (Orphanet:1387), Craniosynostosis (Orphanet:1531), Rosette-forming glioneuronal tumor (Orphanet:251975), Lobar holoprosencephaly (Orphanet:93924), Microform holoprosencephaly (Orphanet:280200), Semilobar holoprosencephaly (Orphanet:220386)

HPO phenotypes

408 total (30 of 408 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000013	Hypoplasia of the uterus
HP:0000023	Inguinal hernia
HP:0000026	Male hypogonadism
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000040	Long penis
HP:0000041	Chordee
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000104	Renal agenesis
HP:0000118	Phenotypic abnormality
HP:0000119	Abnormality of the genitourinary system
HP:0000125	Pelvic kidney
HP:0000126	Hydronephrosis
HP:0000134	Female hypogonadism
HP:0000144	Decreased fertility
HP:0000161	Median cleft upper lip
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000238	Hydrocephalus

GWAS associations

61 associations (top):

Study	Trait	p-value
GCST001106_1	Atopic dermatitis	6.000000e-12
GCST001960_3	Eating disorders	2.000000e-06
GCST002100_1	Atopic dermatitis	9.000000e-11
GCST002737_1	Atopic dermatitis	2.000000e-25
GCST003180_3	Atopic march	9.000000e-11
GCST003184_30	Atopic dermatitis	6.000000e-29
GCST003469_12	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06
GCST004166_30	Nonsyndromic cleft lip with cleft palate	4.000000e-08
GCST004521_242	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST005038_32	Allergic disease (asthma, hay fever or eczema)	7.000000e-21
GCST006218_19	Erosive tooth wear (severe vs non-severe)	8.000000e-09
GCST006218_20	Erosive tooth wear (severe vs non-severe)	2.000000e-08
GCST006218_21	Erosive tooth wear (severe vs non-severe)	2.000000e-08
GCST006218_22	Erosive tooth wear (severe vs non-severe)	2.000000e-08
GCST006218_97	Erosive tooth wear (severe vs non-severe)	6.000000e-06
GCST006218_98	Erosive tooth wear (severe vs non-severe)	6.000000e-06
GCST006226_22	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST006226_23	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST006661_183	Male-pattern baldness	1.000000e-10
GCST006803_65	Schizophrenia	6.000000e-10
GCST006911_7	Asthma (moderate or severe)	1.000000e-08
GCST007045_31	PR interval	5.000000e-10
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST007798_8	Asthma	1.000000e-30
GCST007994_25	Asthma (age of onset)	8.000000e-27
GCST007995_26	Asthma (childhood onset)	2.000000e-65
GCST008103_171	Bipolar disorder	7.000000e-06
GCST008362_177	Birth weight	8.000000e-11
GCST008916_75	Asthma	2.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007755	atopic march
EFO:0007820	cognitive behavioural therapy
EFO:0003959	cleft lip
EFO:0004462	PR interval
EFO:0004344	birth weight
EFO:0004530	triglyceride measurement
EFO:0004327	electrocardiography
EFO:0004847	age at onset
EFO:0009819	comparative body size at age 10, self-reported
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (19)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D001254	Astrocytoma	C04.557.465.625.600.380.080; C04.557.470.670.380.080; C04.557.580.625.600.380.080
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380
D007057	Ichthyosis	C16.131.831.512; C16.614.492; C17.800.428.333; C17.800.804.512
D016112	Ichthyosis Vulgaris	C16.131.831.512.410; C16.320.850.405; C17.800.428.333.410; C17.800.804.512.410; C17.800.827.405
D007246	Infertility	C12.100.750
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
D025962	Septo-Optic Dysplasia	C10.292.562.700.375.875; C10.500.034.937; C10.500.760.500; C11.590.436.400.875; C16.131.666.034.937; C16.131.666.763.500
C562568	Cerebellar Hypoplasia (supp.)
C565293	Dermatitis, Atopic, 2 (supp.)
C535736	Encephalocraniocutaneous lipomatosis (supp.)
C564484	Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip-Palate (supp.)
C563185	Hyperhidrosis Palmaris Et Plantaris (supp.)
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)
C537559	Jackson-Weiss syndrome (supp.)
C536028	Martsolf syndrome (supp.)
C566121	Orofacial Cleft 1 (supp.)
C536050	Osteoglophonic dwarfism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095217 (PROTEIN FAMILY), CHEMBL2111439 (PROTEIN FAMILY), CHEMBL3650 (SINGLE PROTEIN), CHEMBL5291677 (PROTEIN-PROTEIN INTERACTION), CHEMBL5291688 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

93 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 238,521 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL4297522	PEMIGATINIB	4	2,055
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3039504	NINTEDANIB ESYLATE	4	659
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3545376	ERDAFITINIB	4	2,794
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL3701238	FUTIBATINIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL223360	LINIFANIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL2316582	OLVEREMBATINIB	3
CHEMBL270995	BRIVANIB ALANINATE	3
CHEMBL274654	ORANTINIB	3

Clinical evidence (CIViC)

Drug × variant × indication: 37 predictive associations from 38 curated evidence items; also 12 prognostic, 1 functional, 1 oncogenic, 1 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation	Pemigatinib	Myeloid Neoplasm	Sensitivity/Response	CIViC A	EID11324
ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation	Pemigatinib	Lymphoid Leukemia	Sensitivity/Response	CIViC A	EID12241
ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation	Pemigatinib	Lymphoma	Sensitivity/Response	CIViC A	EID12242
FGFR1 Amplification	Dovitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID12478 +1
FGFR1 Amplification	Erdafitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID12469
FGFR1 Amplification	Sunitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID12479
FGFR1 Amplification	Endocrine Drug Therapy + Everolimus	Breast Cancer	Sensitivity/Response	CIViC B	EID12498
FGFR1 Amplification	Fulvestrant + Lucitanib	Estrogen-receptor Positive Breast Cancer	Sensitivity/Response	CIViC B	EID12751
FGFR1 Amplification	Infigratinib	Lung Squamous Cell Carcinoma	Sensitivity/Response	CIViC B	EID1908
FGFR1 Amplification	Dovitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID3027
FGFR1 Amplification	Lucitanib	Breast Cancer	Sensitivity/Response	CIViC B	EID7488
FGFR1 Amplification	Infigratinib	Breast Cancer	Resistance	CIViC B	EID1909
FGFR1 Amplification	Palbociclib + Erdafitinib + Fulvestrant	Breast Cancer		CIViC B	EID12485
FGFR1 Amplification	Lucitanib	Breast Cancer		CIViC B	EID12488
FGFR1 Amplification	Pemigatinib	Breast Cancer	Sensitivity/Response	CIViC C	EID12542
FGFR1 Amplification	Infigratinib	Bladder Carcinoma	Sensitivity/Response	CIViC C	EID1911
FGFR1 Amplification	Fexagratinib	Breast Cancer	Sensitivity/Response	CIViC C	EID1991
FGFR1 Amplification	Pazopanib	Breast Cancer	Sensitivity/Response	CIViC C	EID7246
FGFR1 Amplification	Pazopanib	Adenosquamous Lung Carcinoma	Sensitivity/Response	CIViC C	EID7811
FGFR1 N546K	Pemigatinib	Pilocytic Astrocytoma	Sensitivity/Response	CIViC C	EID10325
FGFR1 Amplification	Ponatinib	Ewing Sarcoma Of Bone	Sensitivity/Response	CIViC D	EID1247
FGFR1 Amplification	Rogaratinib + Palbociclib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC D	EID12503
FGFR1 Amplification	Futibatinib	Breast Cancer	Sensitivity/Response	CIViC D	EID12547
FGFR1 Amplification	Ponatinib	Estrogen-receptor Positive Breast Cancer	Sensitivity/Response	CIViC D	EID1767
FGFR1 Amplification	PD173074	Lung Squamous Cell Carcinoma	Sensitivity/Response	CIViC D	EID680
FGFR1 Amplification	PD173074	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID686
FGFR1 Amplification	Erdafitinib	Lung Cancer	Sensitivity/Response	CIViC D	EID7954
FGFR1 Expression	Fexagratinib + FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074 + Infigratinib	Sarcoma	Sensitivity/Response	CIViC D	EID2915
FGFR1 Expression	Ponatinib	Lung Cancer	Sensitivity/Response	CIViC D	EID681
FGFR1 Expression	Infigratinib	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC D	EID799

+7 more predictive associations (showing top 30 by evidence level).

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type V RTKs: FGF (fibroblast growth factor) receptor family

Most potent curated ligand interactions (45 total), top 25:

Ligand	Action	Affinity	Parameter
TYRA-200	Inhibition	10.0	pKd
risimtinib	Inhibition	10.0	pIC50
segigratinib	Inhibition	9.3	pIC50
pegozafermin	Agonist	9.22	pEC50
fexagratinib	Inhibition	9.15	pIC50
infigratinib	Inhibition	9.05	pIC50
erdafitinib	Inhibition	8.94	pIC50
PRN1371	Inhibition	8.82	pIC50
tinengotinib	Inhibition	8.64	pIC50
LY2874455	Inhibition	8.55	pIC50
compound 7r [PMID: 26080733]	Inhibition	8.54	pIC50
futibatinib	Inhibition	8.44	pIC50
compound 8i [PMID: 22765894]	Inhibition	8.4	pIC50
FGF-21	Agonist	8.35	pEC50
derazantinib	Inhibition	8.35	pIC50
tasurgratinib	Inhibition	8.24	pIC50
compound 8h [PMID: 22765894]	Inhibition	8.24	pIC50
fanregratinib	Inhibition	8.22	pIC50
lucitanib	Inhibition	8.15	pIC50
dovitinib	Inhibition	8.1	pIC50
compound 2c [PMID: 24900538]	Inhibition	8.06	pIC50
zoligratinib	Inhibition	8.04	pIC50
rogaratinib	Inhibition	7.91	pKi
CEP-11981	Inhibition	7.89	pIC50
catequentinib	Inhibition	7.7	pIC50

Binding affinities (BindingDB)

1779 measured of 2560 human assays (2565 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-Phenylbenzimidazole deriv. 76	EC50	0.00399 nM
6-[(2-Aminoethoxy)methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,14][1,2,4]-triazin-4-amine dihydrochloride	IC50	0.2 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-6-[(4-methylpiperazin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.3 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(2,5-dimethylpyrrolidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.32 nM	US-8829199: Aminopyrazole derivative
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(2,5-dimethylpyrrolidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.32 nM	US-10689705: FGFR3 fusion gene and pharmaceutical drug targeting same
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-5-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.355 nM	US-9757364: Naphthyridine derivative compounds
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1H-pyrazol-5-ylmethyl)-1,5-naphthyridin-2-amine	IC50	0.417 nM	US-9757364: Naphthyridine derivative compounds
8-chloro-N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.447 nM	US-9757364: Naphthyridine derivative compounds
6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.5 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-6-(1,3-oxazol-5-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.5 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
8-(2-((1-acryloylazetidin-3-yl)oxy)ethyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.5 nM	US-9815834: Quinolone derivatives as fibroblast growth factor receptor inhibitors
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.501 nM	US-9757364: Naphthyridine derivative compounds
4-(2-fluoro-3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)butanenitrile	IC50	0.55 nM	US-9757364: Naphthyridine derivative compounds
5-(7-Methoxy-5-methyl-1-benzothiophen-2-yl)-6-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine trihydrochloride	IC50	0.6 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
4-{[4-Amino-5-(5-chloro-7-methoxy-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methyl}-piperazin-2-one	IC50	0.6 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
[5-[(E)-2-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]-2-pyridinyl]-imino-methyl-oxo-lambda6-sulfane	KD	0.6 nM	US-12441707: Indazole compounds
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(4-fluoropiperidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.67 nM	US-8829199: Aminopyrazole derivative
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(3-fluoropiperidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.67 nM	US-10689705: FGFR3 fusion gene and pharmaceutical drug targeting same
N-(3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-piperidin-4-yl-1,5-naphthyridin-2-amine	IC50	0.676 nM	US-9757364: Naphthyridine derivative compounds
6-(cyclopropylmethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.7 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
8-(2-((1-acryloylazetidin-3-yl)(methyl)amino)ethyl)-2-amino-6-(2,6-dichloro-3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.7 nM	US-9815834: Quinolone derivatives as fibroblast growth factor receptor inhibitors
N-{[4-Amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]-methyl}acetamide	IC50	0.7 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
6-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.7 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
1-(2-((1-acryloylazetidin-3-yl)(2-methoxyethyl)amino)ethyl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-7-(methylamino)-1,6-naphthyridin-2(1H)-one	IC50	0.7 nM	US-10294223: Quinolone derivatives as fibroblast growth factor receptor inhibitors
2-(N-[8-chloro-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-3,5-dimethoxyanilino)ethanol	IC50	0.724 nM	US-9757364: Naphthyridine derivative compounds
3-(N-[8-chloro-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-3,5-dimethoxyanilino)propan-1-ol	IC50	0.794 nM	US-9757364: Naphthyridine derivative compounds
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[6-[(3-methyloxetan-3-yl)methoxy]-1H-indol-2-yl]methanone	IC50	0.81 nM	US-8829199: Aminopyrazole derivative
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1,3-oxazol-2-ylmethyl)-1,5-naphthyridin-2-amine	IC50	0.851 nM	US-9757364: Naphthyridine derivative compounds
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-pyridin-4-yl-1,5-naphthyridin-2-amine	IC50	0.851 nM	US-9757364: Naphthyridine derivative compounds
6-(methoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.9 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
2-[[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methoxy]ethanol	IC50	0.9 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
6-(cyclobutyloxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.9 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(((1r,4r)-4-hydroxycyclohexyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.9 nM	US-10294223: Quinolone derivatives as fibroblast growth factor receptor inhibitors
8-(2-((1-acryloylazetidin-3-yl)amino)ethyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.9 nM	US-10294223: Quinolone derivatives as fibroblast growth factor receptor inhibitors
(3S)-3-({[4-Amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]-methyl}amino)pyrrolidin-2-one dihydrochloride	IC50	0.9 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
6-[[3-(dimethylamino)piperidin-1-yl]methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.9 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
[5-[(E)-2-[5-[1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]-2-pyridinyl]imino-dimethyl-oxo-lambda6-sulfane	KD	0.9 nM	US-12441707: Indazole compounds
N’-(2,6-difluoro-3,5-dimethoxyphenyl)-N-methyl-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]ethane-1,2-diamine	IC50	0.912 nM	US-9757364: Naphthyridine derivative compounds
5-[(2,6-difluoro-3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)methyl]pyrrolidin-2-one	IC50	0.955 nM	US-9757364: Naphthyridine derivative compounds
N’-(2,6-difluoro-3,5-dimethoxyphenyl)-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-N-propan-2-ylethane-1,2-diamine	IC50	0.977 nM	US-9757364: Naphthyridine derivative compounds
7-[[(3S)-3-amino-3-methylpyrrolidin-1-yl]methyl]-6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	1 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
2-[[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methoxy]acetamide	IC50	1 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
N-[[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methyl]acetamide	IC50	1 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2-chloro-6-fluoro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	1 nM	US-10294223: Quinolone derivatives as fibroblast growth factor receptor inhibitors
(R)-8-(2-((1-acryloylazetidin-3-yl)(methyl)amino)ethyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-((1-methoxypropan-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	1 nM	US-9815834: Quinolone derivatives as fibroblast growth factor receptor inhibitors
1-(3-(4-acryloylpiperazin-1-yl)propyl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-7-((2-(2-methoxyethoxy)ethyl)amino)-1,6-naphthyridin-2(1H)-one	IC50	1 nM	US-9567334: Quinolone derivatives as fibroblast growth factor receptor inhibitors
2-({[4-Amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]-methyl}amino)ethanol dihydrochloride	IC50	1 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
6-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	1 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
2-[(3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)methyl]-N,N-dimethylimidazole-1-sulfonamide	IC50	1 nM	US-9757364: Naphthyridine derivative compounds

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5951244
9.92	IC50	0.12	nM	CHEMBL4870179
9.77	IC50	0.17	nM	CHEMBL4862823
9.74	IC50	0.18	nM	CHEMBL5177696
9.74	IC50	0.18	nM	CHEMBL5556891
9.70	IC50	0.2	nM	CHEMBL3827818
9.70	IC50	0.2	nM	FEXAGRATINIB
9.70	IC50	0.2	nM	CHEMBL4102642
9.70	IC50	0.2	nM	CHEMBL4557949
9.70	IC50	0.2	nM	CHEMBL4542061
9.70	IC50	0.2	nM	CHEMBL5189383
9.70	Kd	0.2	nM	FEXAGRATINIB
9.70	IC50	0.2	nM	CHEMBL5557389
9.70	IC50	0.2	nM	CHEMBL5936783
9.66	IC50	0.22	nM	CHEMBL5558932
9.64	IC50	0.23	nM	CHEMBL5178408
9.62	IC50	0.24	nM	CHEMBL5187998
9.62	IC50	0.24	nM	CHEMBL5181688
9.60	IC50	0.25	nM	CHEMBL5186645
9.60	IC50	0.25	nM	CHEMBL5505835
9.60	IC50	0.25	nM	ERDAFITINIB
9.59	IC50	0.26	nM	CHEMBL5202576
9.57	IC50	0.27	nM	CHEMBL5186714
9.55	IC50	0.28	nM	CHEMBL4100258
9.55	IC50	0.28	nM	CHEMBL5182360
9.52	IC50	0.3	nM	LY-2874455
9.52	IC50	0.3	nM	CHEMBL3827492
9.52	Kd	0.3	nM	ORANTINIB
9.52	IC50	0.3	nM	CHEMBL4461734
9.52	IC50	0.3	nM	CHEMBL4553127
9.52	IC50	0.3	nM	CHEMBL4469836
9.52	IC50	0.3	nM	CHEMBL4447575
9.52	IC50	0.3	nM	CHEMBL4447359
9.52	IC50	0.3	nM	CHEMBL6008228
9.52	IC50	0.3	nM	CHEMBL6049146
9.49	IC50	0.32	nM	CHEMBL3681271
9.49	IC50	0.32	nM	CHEMBL5191744
9.48	IC50	0.33	nM	CHEMBL5556836
9.47	IC50	0.34	nM	CHEMBL5505810
9.46	IC50	0.35	nM	CHEMBL5206740
9.45	IC50	0.355	nM	CHEMBL5799893
9.44	IC50	0.3631	nM	CHEMBL3980069
9.44	IC50	0.36	nM	CHEMBL5542848
9.44	IC50	0.36	nM	CHEMBL5523440
9.43	IC50	0.37	nM	CHEMBL5173348
9.43	IC50	0.37	nM	CHEMBL5170945
9.42	IC50	0.38	nM	CHEMBL5198510
9.42	IC50	0.38	nM	CHEMBL5202912
9.40	IC50	0.4	nM	CHEMBL190161
9.40	IC50	0.4	nM	CHEMBL3828439

PubChem BioAssay actives

2105 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
7-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]quinazolin-4-amine	1298524: Inhibition of FGFR1 in human KG1 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0002	uM
4-[2-[5-[1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-3H-benzimidazol-5-yl]morpholine	1313605: Inhibition of recombinant human FGFR1 using poly (Glu, Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0002	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(4-methylsulfonylpiperazin-1-yl)benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0002	uM
4-(4-cyclobutylpiperazin-1-yl)-N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0002	uM
N’-(3,5-dimethoxyphenyl)-N’-[2-(1-methylpyrazol-4-yl)quinoxalin-6-yl]-N-propan-2-ylethane-1,2-diamine	1849314: Inhibition of recombinant human FGFR1 using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0002	uM
7-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxyheptanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0002	uM
5-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxypentanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0002	uM
4-[2-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]ethoxy]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0002	uM
6-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxyhexanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0002	uM
N-[4-[[6-(3,5-dimethoxyphenyl)purin-9-yl]methyl]phenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0002	uM
N-[5-[(6-bromoindazol-1-yl)methyl]-2-fluorophenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0002	uM
N-[5-[(5-chloroimidazo[4,5-b]pyridin-3-yl)methyl]-2-fluorophenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0002	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide	1298524: Inhibition of FGFR1 in human KG1 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0002	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-[4-(2-methoxyethyl)piperazin-1-yl]benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
1-[3-[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]pyrrolidin-1-yl]prop-2-yn-1-one	1584377: Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
1-[3-[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]pyrrolidin-1-yl]prop-2-en-1-one	1584377: Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
7-(1-ethenylsulfonylazetidin-3-yl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,3-d]pyrimidin-4-amine	1584377: Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-4-yl]-7-(4-methoxyanilino)-4H-pyrimido[4,5-d]pyrimidin-2-one	1460986: Inhibition of human recombinant His-tagged FGFR1 cytoplasmic domain (308 to 731 residues) expressed in baculovirus using Tyr-4 peptide after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0003	uM
N-[2-[5-[1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-3H-benzimidazol-5-yl]-N’,N’-dimethylethane-1,2-diamine	1313605: Inhibition of recombinant human FGFR1 using poly (Glu, Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
1-[(3S)-3-[4-amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]pyrrolidin-1-yl]prop-2-en-1-one	1584377: Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-[4-(2-hydroxyethyl)piperazin-1-yl]benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
4-(4-acetylpiperazin-1-yl)-N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
3-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxypropanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
4-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxybutanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
3-[[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]methyl]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
9-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxynonanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
8-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxyoctanamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
4-[3-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]propoxy]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0003	uM
1-[(3S)-3-[8-amino-1-(5-bromo-7-methoxy-1-benzothiophen-2-yl)imidazo[1,5-a]pyrazin-3-yl]pyrrolidin-1-yl]prop-2-en-1-one	1939966: Inhibition of human recombinant FGFR1	ic50	0.0003	uM
N-[5-[(6-bromoindol-1-yl)methyl]-2-fluorophenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0003	uM
methyl 1-[[4-fluoro-3-(prop-2-enoylamino)phenyl]methyl]benzotriazole-4-carboxylate	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0003	uM
N-[4-[[6-(3,4-difluorophenyl)purin-9-yl]methyl]phenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0003	uM
2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol	1313605: Inhibition of recombinant human FGFR1 using poly (Glu, Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid	1425004: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0003	uM
6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[2-(1-prop-2-enoylazetidin-3-yl)oxyethyl]pyrido[2,3-d]pyrimidin-7-one	1446127: Inhibition of human FGFR1 using 5-FAM-KKKKEEIYFFF-NH2 as substrate preincubated for 15 mins followed by peptide substrate addition measured after 3 hrs by caliper capillary electrophoresis method	ic50	0.0004	uM
N-[2-[5-[1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]-3H-benzimidazol-5-yl]-2-(dimethylamino)-N-methylacetamide	1313605: Inhibition of recombinant human FGFR1 using poly (Glu, Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0004	uM
(E)-N-[4-[4-amino-3-(5-bromo-3-methyl-1-benzofuran-2-yl)-7-oxo-6H-pyrazolo[3,4-d]pyridazin-2-yl]phenyl]-4-(dimethylamino)but-2-enamide	1516661: Inhibition of human FGFR1 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA	ic50	0.0004	uM
4-[2-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]ethyl]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0004	uM
4-[4-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]butoxy]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0004	uM
4-[5-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]pentoxy]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0004	uM
4-[3-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]propanoylamino]-N-hydroxybenzamide	1897367: Inhibition of FGFR1 (unknown origin)	ic50	0.0004	uM
2-[5-[2-(2,6-dichloro-3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole	1845246: Inhibition of recombinant N-terminal GST-tagged human FGFR1 (398 to 822 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay	ic50	0.0004	uM
N-[5-[(5-bromopyrrolo[2,3-b]pyridin-1-yl)methyl]-2-fluorophenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-[(6-chloropurin-9-yl)methyl]phenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-[[6-(1-benzothiophen-2-yl)purin-9-yl]methyl]phenyl]prop-2-enamide	2063026: Inhibition of FGFR1 (unknown origin) by ELISA	ic50	0.0004	uM
1-tert-butyl-3-[3-(3,5-dimethoxyphenyl)-7-[4-(4-methylpiperazin-1-yl)butylamino]-1,6-naphthyridin-2-yl]urea	248789: Inhibition of FGF-dependent human umbilical vein endothelial cell proliferation	ic50	0.0004	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(4-ethylpiperazin-1-yl)benzamide	1626462: Inhibition of recombinant human FGFR1 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0005	uM
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(3,3-dimethylpiperazin-1-yl)benzamide	1937908: Inhibition of N-terminal GST tagged recombinant human FGFR1 (456 to 765 residues) expressed in baculovirus infected Sf21 cells by ELISA analysis	ic50	0.0005	uM
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(5-morpholin-4-yl-3-pyridinyl)ethynyl]benzamide	1435442: Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu, Tyr) 4:1 after 60 mins by ELISA method	ic50	0.0005	uM

CTD chemical–gene interactions

104 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, increases reaction, decreases phosphorylation, increases expression, decreases response to substance	6
Benzo(a)pyrene	increases mutagenesis, decreases expression, increases expression, increases methylation	5
SU 5402	decreases activity	4
ponatinib	decreases phosphorylation, decreases activity	4
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	3
Particulate Matter	affects expression, increases abundance, increases expression	3
futibatinib	decreases activity	2
bisphenol A	decreases methylation, increases expression	2
PD 173074	decreases expression, increases reaction, decreases activity, decreases phosphorylation, decreases reaction (+1 more)	2
entinostat	affects cotreatment, increases expression	2
bisphenol S	affects cotreatment, decreases methylation, decreases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression, affects cotreatment	2
Hydrogen Peroxide	increases reaction, decreases expression, affects binding	2
Heparan Sulfate Proteoglycans	affects binding, increases activity, increases reaction	2
methylmercuric chloride	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
lead acetate	affects cotreatment, increases expression	1
piperine	affects binding	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	affects expression	1

ChEMBL screening assays

1465 unique, capped per target: 1428 binding, 24 functional, 13 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1249398	Binding	Inhibition of FGFR signaling-induced STAT3 tyr705 phosphorylation in human U2OS cells at 50 nM by immunoblot analysis	A functional genomics approach to the mode of action of apratoxin A. — Nat Chem Biol
CHEMBL678499	Functional	Inhibition of fibroblast growth factor receptor(FGFR)	Tyrosine kinase inhibitors. 14. Structure-activity relationships for methylamino-substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase activity of receptors for the EGF family of growth factors. — J Med Chem
CHEMBL4018312	ADMET	Inhibition of recombinant human His-tagged FGFR1 cytoplasmic domain (308 to 731 residues) expressed in baculovirus expression system using tyr 04 as substrate measured within 60 mins by Z-LYTE assay	Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping. — Bioorg Med Chem Lett

Cellosaurus cell lines

22 cell lines: 20 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0374	KG-1	Cancer cell line	Male
CVCL_0445	MeWo	Cancer cell line	Male
CVCL_1824	KG-1a	Cancer cell line	Male
CVCL_5301	KMT-2	Cancer cell line	Male
CVCL_B2X3	Abcam HEK293T FGFR1 KO	Transformed cell line	Female
CVCL_B5PF	MCF7-FGFR1	Cancer cell line	Female
CVCL_D1SE	Abcam U-87MG FGFR1 KO	Cancer cell line	Male
CVCL_D8LB	Ubigene HCT 116 FGFR1 KO	Cancer cell line	Male
CVCL_D9EU	Ubigene HEK293 FGFR1 KO	Transformed cell line	Female
CVCL_D9W7	Ubigene HGC-27 FGFR1 KO	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

157 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00140413	PHASE4	COMPLETED	Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT06760546	PHASE3	RECRUITING	A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
NCT01739582	PHASE3	COMPLETED	An Extension Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01739595	PHASE3	COMPLETED	Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
NCT01993212	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT01993225	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT02110368	PHASE3	COMPLETED	Bioequivalence Study of Test and Reference Testosterone Topical Gel, 1.62% Metered Pump in Testosterone Deficient Adult Male Subjects Under Fasting Conditions
NCT03019575	PHASE3	COMPLETED	Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH) (MK-8962-043)
NCT06561594	PHASE3	NOT_YET_RECRUITING	To Evaluate Recombinant Human Follicle Stimulating Hormone-CTP Fusion Protein Injection or Placebo Combined With Chorionic Gonadotropin for Injection
NCT00827151	PHASE3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00193661	PHASE2	COMPLETED	Observation Study of T-Gel (1%) in Treatment of Adolescent Boys With Hypogonadism
NCT00383656	PHASE2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00697814	PHASE2	COMPLETED	Clomiphene in Males With Prolactinomas and Persistent Hypogonadism
NCT00706719	PHASE2	COMPLETED	To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone
NCT00911586	PHASE2	COMPLETED	Pharmacokinetic Study to Determine Time to Steady-state
NCT01155518	PHASE2	TERMINATED	Hypogonadism in Young Men With Type 2 Diabetes
NCT01191320	PHASE2	COMPLETED	Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus
NCT01270841	PHASE2	COMPLETED	Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism