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) — +14 more curated relationships
• GWAS associations: 61 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 1,578 total — 157 pathogenic, 116 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 10 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 29 (q < 0.05)
• Phenotypes (HPO): 408
• Drug target: yes — 11 curated mechanism-of-action drugs, 14 via a complex or family; 93 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 3 — Pazopanib Hydrochloride, Pemigatinib, Regorafenib
• Approved drugs acting on a complex or family including it: 4 — Erdafitinib, Futibatinib, Infigratinib, +1 more (Fibroblast growth factor receptor)
• Precision-oncology evidence (CIViC): 37 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 11.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.27 (highly constrained)
• MANE Select transcript: NM_023110
• Interaction hub: 3,541 STRING partners (top 1% of genes corpus-wide)

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: 78 — 40 protein_coding, 21 retained_intron, 11 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined

MANE Select: ENST00000447712

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 13, TSL 2: 4, TSL 3: 9, TSL 4: 8, TSL 5: 8

ENST00000447712, ENST00000326324, ENST00000335922, ENST00000341462, ENST00000356207, ENST00000397090, ENST00000397091, ENST00000397103, ENST00000397108, ENST00000397113, ENST00000413133, ENST00000425967, ENST00000434187, ENST00000440174, 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, ENST00001027306, ENST00001067623, ENST00001067624, ENST00001067625, ENST00001133667

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.

Highest expression (Bgee): buccal mucosa cell, stromal cell of endometrium, calcaneal tendon, ovary, paraflocculus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FGFR1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 29 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 48 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.5e-42	+0.44	8:38469790:G:T
Artery Tibial	sqtl	3.3e-35	-0.73	8:38429293:C:G
Nerve Tibial	sqtl	4.5e-33	-0.71	8:38429293:C:G
Adipose Visceral Omentum	sqtl	5.8e-29	-0.62	8:38430037:C:T
Esophagus Muscularis	sqtl	1.7e-26	-0.69	8:38434948:A:T
Colon Sigmoid	sqtl	3.7e-25	-0.68	8:38429293:C:G
Adipose Subcutaneous	sqtl	1.1e-24	-0.58	8:38429293:C:G
Brain Cerebellum	sqtl	3.0e-20	+0.93	8:38429293:C:G
Esophagus Gastroesophageal Junction	sqtl	1.1e-18	-0.73	8:38429293:C:G
Artery Aorta	sqtl	3.8e-18	-0.64	8:38429293:C:G
Lung	sqtl	4.1e-17	-0.66	8:38429293:C:G
Breast Mammary Tissue	sqtl	4.1e-17	-0.65	8:38429293:C:G
Pancreas	sqtl	1.6e-14	-0.75	8:38429293:C:G
Testis	sqtl	8.6e-14	-0.72	8:38263203:T:C
Heart Atrial Appendage	sqtl	5.3e-11	-0.56	8:38441129:C:T
Brain Cerebellar Hemisphere	sqtl	6.2e-10	-0.86	8:38429293:C:G
Thyroid	sqtl	1.5e-09	-0.47	8:38426493:C:T
Colon Transverse	sqtl	1.8e-08	-0.53	8:38429293:C:G
Prostate	sqtl	1.9e-08	-0.71	8:38272507:G:A
Ovary	sqtl	2.5e-08	-0.79	8:38430037:C:T

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

showing 100 of 294 tissues 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
left coronary artery	UBERON:0001626	97.82	gold quality
endothelial cell	CL:0000115	97.81	gold quality
smooth muscle tissue	UBERON:0001135	97.80	gold quality
body of uterus	UBERON:0009853	97.80	gold quality
dorsal root ganglion	UBERON:0000044	97.79	gold quality
endocervix	UBERON:0000458	97.78	gold quality
trigeminal ganglion	UBERON:0001675	97.78	gold quality
periodontal ligament	UBERON:0008266	97.75	gold quality
nipple	UBERON:0002030	97.73	gold quality
cartilage tissue	UBERON:0002418	97.70	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.68	gold quality
synovial joint	UBERON:0002217	97.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.56	gold quality
pericardium	UBERON:0002407	97.50	gold quality
vena cava	UBERON:0004087	97.42	gold quality
olfactory bulb	UBERON:0002264	97.40	gold quality
right atrium auricular region	UBERON:0006631	97.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.27	gold quality
layer of synovial tissue	UBERON:0007616	97.22	gold quality
cardiac atrium	UBERON:0002081	97.06	gold quality
urethra	UBERON:0000057	97.05	gold quality
myometrium	UBERON:0001296	97.02	gold quality
pancreas	UBERON:0001264	96.99	gold quality
ovary	UBERON:0000992	96.85	gold quality
ventricular zone	UBERON:0003053	96.82	gold quality
pituitary gland	UBERON:0000007	96.71	gold quality
apex of heart	UBERON:0002098	96.66	gold quality
trachea	UBERON:0003126	96.66	gold quality
adipose tissue	UBERON:0001013	96.63	gold quality
adenohypophysis	UBERON:0002196	96.58	gold quality
connective tissue	UBERON:0002384	96.54	gold quality
type B pancreatic cell	CL:0000169	96.49	gold quality
islet of Langerhans	UBERON:0000006	96.46	gold quality
heart	UBERON:0000948	96.38	gold quality
heart left ventricle	UBERON:0002084	96.20	gold quality
ectocervix	UBERON:0012249	96.20	gold quality
sural nerve	UBERON:0015488	96.17	gold quality
blood vessel layer	UBERON:0004797	96.15	gold quality
cardiac ventricle	UBERON:0002082	96.14	gold quality
mammary duct	UBERON:0001765	95.97	gold quality
right lung	UBERON:0002167	95.85	gold quality
upper lobe of left lung	UBERON:0008952	95.70	gold quality
urinary bladder	UBERON:0001255	95.68	gold quality
upper lobe of lung	UBERON:0008948	95.59	gold quality
epithelium of mammary gland	UBERON:0003244	95.47	gold quality
right uterine tube	UBERON:0001302	95.46	gold quality
embryo	UBERON:0000922	95.15	gold quality
fundus of stomach	UBERON:0001160	95.13	gold quality
male germ cell	CL:0000015	95.00	gold quality
tendon	UBERON:0000043	95.00	gold quality
mammalian vulva	UBERON:0000997	94.93	gold quality
sperm	CL:0000019	94.90	gold quality
pons	UBERON:0000988	94.80	gold quality
superior vestibular nucleus	UBERON:0007227	94.78	gold quality
pylorus	UBERON:0001166	94.71	gold quality
tibia	UBERON:0000979	94.50	gold quality
vagina	UBERON:0000996	94.36	gold quality
mammary gland	UBERON:0001911	94.21	gold quality
cerebellar vermis	UBERON:0004720	94.19	gold quality
thoracic mammary gland	UBERON:0005200	94.14	gold quality
superficial temporal artery	UBERON:0001614	94.12	gold quality
cardia of stomach	UBERON:0001162	94.10	gold quality
ganglionic eminence	UBERON:0004023	94.10	gold quality
lower lobe of lung	UBERON:0008949	94.09	gold quality
mucosa of urinary bladder	UBERON:0001259	94.06	gold quality
prostate gland	UBERON:0002367	93.95	gold quality
medulla oblongata	UBERON:0001896	93.91	gold quality
uterine cervix	UBERON:0000002	93.84	gold quality
lung	UBERON:0002048	93.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.73	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 112 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	432.6	high
Cerebellum	tissue	174.3	medium
Locus coeruleus	tissue	133.1
Choroid plexus	tissue	79.9
Pancreas	tissue	78.9	medium
Adipose tissue	tissue	74.7	not detected
Ovary	tissue	67.5	medium
Hippocampus	tissue	60.5	medium
Spinal cord	tissue	59.2
Cervix	tissue	55.9	medium
Pons	tissue	54.0
Heart muscle	tissue	53.7	medium
Smooth muscle	tissue	52.9	medium
Gallbladder	tissue	51.8	high
Seminal vesicle	tissue	50.0	medium
Superior colliculi	tissue	47.8
Placenta	tissue	47.5	high
Medulla oblongata	tissue	45.3
Urinary bladder	tissue	44.3	medium
Periaqueductal gray	tissue	44.2
Fallopian tube	tissue	43.3	high
Substantia nigra	tissue	41.9
Hippocampal formation	tissue	41.1
Midbrain	tissue	39.0
Endometrium 1	tissue	37.6	medium
Vagina	tissue	37.3	medium
Hypothalamus	tissue	37.0
Breast	tissue	35.3	medium
Thalamus	tissue	34.3
Esophagus	tissue	33.6	high
Prostate	tissue	33.3	medium
Pituitary gland	tissue	32.7
Postcentral gyrus	tissue	30.5
Nucleus accumbens	tissue	29.5
Amygdala	tissue	27.4
Septum	tissue	27.3
Frontal cortex	tissue	26.2
Basal ganglia	tissue	24.0	medium
Caudate putamen	tissue	23.2
Corpus callosum	tissue	21.9
Tongue	tissue	21.6
Ventral forebrain	tissue	21.6
Lung	tissue	20.7	medium
Colon	tissue	20.5	medium
Entorhinal cortex	tissue	20.5
Cerebral cortex	tissue	19.7	medium
Temporal cortex	tissue	19.7
Parathyroid gland	tissue	19.5	low
Insular cortex	tissue	18.7
Motor cortex	tissue	18.5
Putamen	tissue	17.9
Prefrontal cortex	tissue	17.6
Olfactory bulb	tissue	17.4
Somatosensory cortex	tissue	16.9
Retrosplenial cortex	tissue	16.9
Rectum	tissue	16.6	medium
Salivary gland	tissue	16.5	medium
Retrosplenial and cingulate cortex	tissue	16.1
Appendix	tissue	16.1	medium
Thymus	tissue	15.4

Brain sub-regions (HPA Brain Atlas): detected in 375; highest nTPM — Flocculonodular lobe (99.9), Blood vessel (86.3), Vermis (85.9), Cerebellar cortex (81.9), Pedunculopontine tegmental nucleus (75.7).

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)

Targeting FGFR1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 121 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.274, missense Z 4.28 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000447712 splits into 10 regions with different missense tolerance; 2 are missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:38,413,631–38,413,957	79 / 97.2	0.81	no
8:38,413,958–38,414,261	35 / 78.0	0.45	no
8:38,414,262–38,414,571	0 / 16.6	0.00	yes (p 4.6e-05)
8:38,414,572–38,415,913	44 / 99.9	0.44	no
8:38,415,914–38,416,008	39 / 39.2	1.00	no
8:38,416,009–38,417,932	62 / 99.5	0.62	no
8:38,417,933–38,417,989	5 / 21.8	0.23	yes (p 3.2e-04)
8:38,417,990–38,421,841	146 / 173.0	0.84	no
8:38,421,842–38,428,085	109 / 249.4	0.44	no
8:38,428,086–38,457,446	212 / 205.8	1.03	no
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.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Li-7 (-2.762), A-172 (-2.18), UM-UC-13 (-2.13), WM3211 (-2.081), UPCI-SCC-029A (-1.983), JMSU-1 (-1.98), MPNST-724 (-1.851), HCC-1359 (-1.79), LNZTA3WT4 (-1.746), CAL-72 (-1.73), SUM-1315MO2 (-1.698), CAL-120 (-1.687), 93T449 (-1.624), NCC-UPS1-C1 (-1.602), HS-Sch-2 (-1.601).

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), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95522) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 259 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic growth retardation	6
embryonic lethality, complete penetrance	6
abnormal developmental patterning	5
abnormal axial skeleton morphology	4
neonatal lethality, complete penetrance	4
small ears	3
abnormal mesoderm development	3
decreased embryo size	3
abnormal extraembryonic tissue morphology	3
abnormal craniofacial bone morphology	3
abnormal neural tube morphology	3
abnormal outer ear morphology	3
caudal body truncation	3
abnormal incus morphology	3
absent somites	3
decreased paraxial mesoderm size	3
abnormal ear shape	2
lowered ear position	2
cleft palate	2
abnormal cartilage development	2
abnormal heart development	2
oligodactyly	2
abnormal midbrain morphology	2
abnormal somite development	2
abnormal gastrulation	2

+234 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Felis catus	A0M8S8	100.0%	Diamond
Neofelis nebulosa	Q07E37	100.0%	Diamond
Pan troglodytes	Q2QLF1	99.8%	Diamond
Gorilla gorilla gorilla	Q2IBF2	99.7%	Diamond
Pongo abelii	Q5RB23	99.7%	Diamond
Bos taurus	P43481	99.4%	Diamond
Capra hircus	Q28317	99.4%	Diamond
Papio anubis	A0M8R7	99.3%	Diamond
Colobus guereza	Q07DZ1	99.3%	Diamond
Chlorocebus aethiops	Q2IBA6	99.3%	Diamond
Aotus nancymaae	Q07DV8	99.1%	Diamond
Nomascus leucogenys	Q07DY1	99.1%	Diamond
Ateles geoffroyi	Q09YL1	99.1%	Diamond
Saimiri boliviensis boliviensis	Q09YH7	99.0%	Diamond
Gallus gallus	P08941	98.7%	Diamond
Plecturocebus moloch	Q2QLC0	98.6%	Diamond
Canis lupus familiaris	O97799	98.4%	Diamond
Sus scrofa	Q2HWD6	98.1%	Diamond
Callithrix jacchus	Q2QLG5	97.7%	Diamond
Ovis aries	Q09YI9	97.5%	Diamond
Muntiacus muntjak	Q09YK0	97.4%	Diamond
Eulemur macaco macaco	Q2IBG7	97.4%	Diamond
Microcebus murinus	Q2QL89	97.4%	Diamond
Mustela putorius furo	Q07E24	96.4%	Diamond
Equus caballus	Q2QLA9	94.9%	Diamond
Otolemur garnettii	Q2QLH6	94.0%	Diamond
Atelerix albiventris	Q00PJ8	92.0%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 4)	P04048	99.2%	Diamond
Feline sarcoma virus (STRAIN MCDONOUGH)	P00545	99.1%	Diamond
UR2 sarcoma virus	P00529	98.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LETM2	protein-coding	137994
DDHD2	protein-coding	23259
LINC03042	ncRNA	389649
NSD3	protein-coding	54904
PLPP5	protein-coding	84513
BAG4	protein-coding	9530
LSM1	protein-coding	27257

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

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

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

UniProt features (241 total): sequence variant 92, strand 42, helix 23, 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)

showing 30 of 86 structures by resolution:

PDB	Title	Method	Resolution (Å)
5EW8	FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693	X-RAY DIFFRACTION	1.63
4WUN	Structure of FGFR1 in complex with AZD4547 …	X-RAY DIFFRACTION	1.65
9U7G	FGFR1 kinase domain with a macrocyclic compound 8g	X-RAY DIFFRACTION	1.66
7OZB	FGFR1 kinase domain (residues 458-765) with mutations C488A, C584S in complex with 38.	X-RAY DIFFRACTION	1.71
8XZ7	FGFR1 kinase domain with a covalent inhibitor 10h	X-RAY DIFFRACTION	1.75
9UHI	FGFR1 kinase domain with a covalent inhibitor 9o	X-RAY DIFFRACTION	1.76
9VLJ	Crystal structure of FGFR1 in complex with covalent inhibitor 10a	X-RAY DIFFRACTION	1.81
7OZD	FGFR1 kinase domain (residues 458-765) with mutations C488A, C584S in complex with 34.	X-RAY DIFFRACTION	1.82
7OZF	FGFR1 kinase domain (residues 458-765) with mutations C488A, C584S in complex with 19.	X-RAY DIFFRACTION	1.82
9UHC	FGFR1 kinase domain with a covalent inhibitor 9p	X-RAY DIFFRACTION	1.88
9WFK	Crystal structure of FGFR1 kinase domain in complex with …	X-RAY DIFFRACTION	1.89
9WGT	Crystal structure of FGFR1 kinase domain in complex with …	X-RAY DIFFRACTION	1.9
5O49	Human FGF in complex with a covalent inhibitor	X-RAY DIFFRACTION	1.91
3DPK	cFMS tyrosine kinase in complex with a pyridopyrimidinone inhibitor	X-RAY DIFFRACTION	1.95
5AM7	FGFR1 mutant with an inhibitor	X-RAY DIFFRACTION	1.96
4UWC	Fibroblast growth factor receptor 1 kinase in complex with JK-P3	X-RAY DIFFRACTION	1.96
5AM6	Native FGFR1 with an inhibitor	X-RAY DIFFRACTION	1.96
9W1A	Crystal structure of FGFR1 with a macrocyclic compound XS8148	X-RAY DIFFRACTION	1.96
8JMZ	FGFR1 kinase domain with sulfatinib	X-RAY DIFFRACTION	1.99
6ITJ	Crystal structure of FGFR1 kinase domain in complex with compound 3	X-RAY DIFFRACTION	1.99
1FGK	CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1	X-RAY DIFFRACTION	2
4ZSA	Crystal structure of FGFR1 kinase domain in complex with 7n	X-RAY DIFFRACTION	2
6C1B	FGFR1 kinase complex with inhibitor SN37118	X-RAY DIFFRACTION	2
6MZQ	TAS-120 in reversible binding mode with FGFR1	X-RAY DIFFRACTION	2
3RHX	Crystal structure of the catalytic domain of FGFR1 kinase in complex with ARQ 069	X-RAY DIFFRACTION	2.01
5O4A	Human FGF in complex with a covalent inhibitor	X-RAY DIFFRACTION	2.01
4F64	Crystal structure of Human Fibroblast Growth Factor Receptor 1 Kinase domain in complex …	X-RAY DIFFRACTION	2.05
3C4F	FGFR TYROSINE KINASE DOMAIN IN COMPLEX WITH 3-(3-methoxybenzyl)-7-azaindole	X-RAY DIFFRACTION	2.07
5A4C	FGFR1 ligand complex	X-RAY DIFFRACTION	2.09
3KRJ	cFMS tyrosine kinase in complex with 4-Cyano-1H-imidazole-2-carboxylic acid …	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, CD markers, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of the musculoskeletal system, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytokinetic bridge; microtubules; mitotic spindle; basal body; centriolar satellite; cytosol; primary cilium

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
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)

Position	Role
484–490	ATP
514	ATP
562–564	ATP
568	ATP
627	ATP
641	ATP

Post-translational modifications (7)

Type	Positions
Phosphotyrosine	463, 583, 585, 653, 654, 730, 766

Disulfide bonds (3)

Type	Positions
Disulfide bond	55–101, 178–230, 277–341

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	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 and stimulation of …

Function

Pathways and Gene Ontology

Reactome pathways

19 curated (TAS) of 28; 9 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

28 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-1839120	Signaling by FGFR1 amplification mutants ⚕	curated
R-HSA-5655302	Signaling by FGFR1 in disease ⚕	curated
R-HSA-1839122	Signaling by activated point mutants of FGFR1 ⚕	curated
R-HSA-8853336	Signaling by plasma membrane FGFR1 fusions ⚕	curated
R-HSA-5654687	Downstream signaling of activated FGFR1	curated
R-HSA-190370	FGFR1b ligand binding and activation	curated
R-HSA-190374	FGFR1c and Klotho ligand binding and activation	curated
R-HSA-190373	FGFR1c ligand binding and activation	curated
R-HSA-5654693	FRS-mediated FGFR1 signaling	curated
R-HSA-5654726	Negative regulation of FGFR1 signaling	curated
R-HSA-5654689	PI-3K cascade:FGFR1	curated
R-HSA-109704	PI3K Cascade	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-5654219	Phospholipase C-mediated cascade: FGFR1	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-5654688	SHC-mediated cascade:FGFR1	curated
R-HSA-445144	Signal transduction by L1	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-1839124	FGFR1 mutant receptor activation ⚕	—
R-HSA-1226099	Signaling by FGFR in disease ⚕	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9758919	Epithelial-Mesenchymal Transition (EMT) during gastrulation	electronic
R-HSA-9793380	Formation of paraxial mesoderm	electronic
R-HSA-9758941	Gastrulation	—
R-HSA-375165	NCAM signaling for neurite out-growth	electronic

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 (39): negative regulation of transcription by RNA polymerase II (GO:0000122), MAPK cascade (GO:0000165), skeletal system development (GO:0001501), neuron migration (GO:0001764), epithelial to mesenchymal transition (GO:0001837), DNA-templated transcription (GO:0006351), protein phosphorylation (GO:0006468), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), positive regulation of phospholipase activity (GO:0010518), cell migration (GO:0016477), peptidyl-tyrosine phosphorylation (GO:0018108), ventricular zone neuroblast division (GO:0021847), fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development (GO:0035607), 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), positive regulation of cell cycle (GO:0045787), protein autophosphorylation (GO:0046777), phosphatidylinositol-mediated signaling (GO:0048015), skeletal system morphogenesis (GO:0048705), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), calcium ion homeostasis (GO:0055074), diphosphate metabolic process (GO:0071344), cementum mineralization (GO:0071529), regulation of postsynaptic density assembly (GO:0099151), response to sodium phosphate (GO:1904383), positive regulation of vascular endothelial cell proliferation (GO:1905564), positive regulation of endothelial cell chemotaxis (GO:2001028), positive regulation of macromolecule metabolic process (GO:0010604), positive regulation of cell communication (GO:0010647), positive regulation of signaling (GO:0023056), generation of neurons (GO:0048699), regulation of primary metabolic process (GO:0080090)

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 (9): 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)

Reactome top-level categories

11 top-level categories:

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

showing 60 of 75 GO namespaces:

Category	Terms
cellular anatomical structure	4
fibroblast growth factor receptor signaling pathway	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
animal gross anatomical part developmental process	1
cell migration	1
generation of neurons	1
mesenchymal cell differentiation	1
gene expression	1
RNA biosynthetic process	1
phosphorylation	1
protein modification process	1
cell population proliferation	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
glycerophospholipase activity	1
regulation of phospholipase activity	1
positive regulation of lipase activity	1
cell motility	1
protein phosphorylation	1
forebrain ventricular zone progenitor cell division	1
forebrain neuroblast division	1
orbitofrontal cortex development	1
embryo development ending in birth or egg hatching	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
cellular response to growth factor stimulus	1
response to fibroblast growth factor	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
protein kinase activity	1
transmembrane receptor protein tyrosine kinase activity	1
fibroblast growth factor binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
growth factor binding	1
protein domain specific binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
signaling receptor binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 22 of 63 annotations. The rest are phylogenetic / computational / electronic (IEA).

22 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to fibroblast growth factor stimulus	BP	direct assay
epithelial to mesenchymal transition	BP	mutant phenotype
fibroblast growth factor receptor signaling pathway	BP	direct assay
peptidyl-tyrosine phosphorylation	BP	direct assay
positive regulation of MAP kinase activity	BP	direct assay
positive regulation of MAPK cascade	BP	mutant phenotype
positive regulation of blood vessel endothelial cell migration	BP	genetic interaction
positive regulation of cell population proliferation	BP	direct assay
positive regulation of endothelial cell chemotaxis	BP	direct assay
positive regulation of neuron differentiation	BP	mutant phenotype
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	genetic interaction
positive regulation of vascular endothelial cell proliferation	BP	genetic interaction
protein autophosphorylation	BP	direct assay
plasma membrane	CC	direct assay
signaling receptor complex	CC	direct assay
fibroblast growth factor binding	MF	direct assay
fibroblast growth factor receptor activity	MF	direct assay
heparin binding	MF	direct assay
identical protein binding	MF	physical interaction
protein homodimerization activity	MF	physical interaction
protein tyrosine kinase activity	MF	direct assay
receptor-receptor interaction	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 3,541 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGFR1	FGF8	P55075	913
FGFR1	FGF2	P09038	908
FGFR1	FGF1	P05230	906
FGFR1	FGF13	Q92913	884
FGFR1	FGF9	P31371	876
FGFR1	FGF4	P08620	868
FGFR1	FGF10	O15520	858
FGFR1	FGF7	P21781	855
FGFR1	FGF23	Q9GZV9	851
FGFR1	FGF3	P11487	850
FGFR1	FGF18	O76093	835
FGFR1	KLB	Q86Z14	834
FGFR1	FGF6	P10767	832
FGFR1	FGF17	O60258	832
FGFR1	TWIST1	Q15672	831
FGFR1	ANOS1	P23352	831

IntAct

Human interaction partners of FGFR1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 48 partners by confidence:

Partner	Interaction type	MIscore	Records
FGF2	direct interaction	0.910	8
PLCG1	phosphorylation reaction	0.900	9
FGF1	direct interaction	0.840	6
NEDD4	direct interaction	0.670	26
HSP90AB1	physical association	0.670	1
PIK3R1	proximity	0.640	5
ANOS1	direct interaction	0.630	5
NOSTRIN	direct interaction	0.630	5
HTR1A	proximity	0.620	6
CTNNB1	physical association	0.620	2
FGFR2	physical association	0.620	1
FRS2	association	0.570	1
CDH1	physical association	0.540	3
FGF23	direct interaction	0.540	1
FGFR4	physical association	0.540	1
CRK	proximity	0.480	2
FGF8	direct interaction	0.440	2
ERBB3	direct interaction	0.440	1
FGF4	direct interaction	0.440	1
FGF6	direct interaction	0.440	1
FGF9	direct interaction	0.440	1
KLB	direct interaction	0.440	1
MFHAS1	direct interaction	0.440	1
NCAM1	direct interaction	0.440	1
PKM	phosphorylation reaction	0.440	1
PTPN11	proximity	0.410	1
FGF19	physical association	0.400	1
HSPD1	physical association	0.400	1
CTPS2	physical association	0.370	1
ANK1	association	0.350	1

BioGRID (1,450 interactions; top human partners by supporting records in a sample of 600 records): FGF2 (Protein-peptide; 24 records), FGF1 (Co-localization; 18 records), PLCG1 (Co-localization; 13 records), FRS2 (Biochemical Activity; 9 records), RPS6KA1 (Two-hybrid; 6 records), CDC37 (Affinity Capture-MS; 5 records), GRB14 (FRET; 5 records), HTR1A (Affinity Capture-Western; 5 records), RPS6KA3 (Affinity Capture-MS; 5 records), CANX (Affinity Capture-MS; 4 records), CD44 (Affinity Capture-Western; 4 records), CREBBP (Co-localization; 4 records), FGFR2 (Affinity Capture-MS; 4 records), HSP90AA1 (Affinity Capture-Western; 4 records), KAL1 (Reconstituted Complex; 4 records)

SIGNOR signaling

showing 36 of 64 signaling 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
FGFR1	“up-regulates activity”	FRS2	phosphorylation
FGFR1	“up-regulates activity”	PCDH15	phosphorylation
FGF5	up-regulates	FGFR1	binding
FGFR1	up-regulates	BCAR1	phosphorylation
FGF1	up-regulates	FGFR1	binding
FGFR1	down-regulates	CTTN	phosphorylation
FGFR1	up-regulates	FGFR1	phosphorylation
FGFR1	down-regulates	SYNCRIP	phosphorylation
FGFR1	“down-regulates activity”	PDP1	phosphorylation
nintedanib	“down-regulates activity”	FGFR1	“chemical inhibition”

Protein complexes (CORUM) (12)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

12 complexes by size:

Complex	Subunits	Members
★ FGFR1-FLT1-VEGFB complex	3	FGFR1, FLT1, VEGFB
★ FGFR1-PKM-RACK1 complex	3	FGFR1, PKM, RACK1
★ FGFR1-FRS2-MTOR complex	3	MTOR, FGFR1, FRS2
★ FGF2-FGFR1-FGFRL1 complex	3	FGFRL1, FGF2, FGFR1
★ FGF21-FGFR1-KLB complex	3	FGF21, FGFR1, KLB
★ FGF1-FGFR1-ITGB3 complex	3	FGF1, FGFR1, ITGB3
★ ANOS1-FGF2-FGFR1 complex	3	ANOS1, FGF2, FGFR1
★ FGFR1-FLT1 complex	2	FGFR1, FLT1
★ FGFR1–GRB14 complex	2	FGFR1, GRB14
★ FGFR1-FGFRL1 complex	2	FGFRL1, FGFR1
★ FGFR1-RPS6KA1 complex	2	FGFR1, RPS6KA1
★ FGFR1-KLB complex	2	FGFR1, KLB

Ligand–receptor pairs (CellPhoneDB) (7)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

7 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
FGFR1;KL		Signaling by Fibroblast growth factor
FGF5	receptor	Signaling by Fibroblast growth factor
FGF6	receptor	Signaling by Fibroblast growth factor
FGF2	receptor	Signaling by Fibroblast growth factor
NCAM1	receptor	Signaling by Fibroblast growth factor
FGF1	receptor	Signaling by Fibroblast growth factor
FGF4	receptor	Signaling by Fibroblast growth factor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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	11	194.8×	1e-22
PI-3K cascade:FGFR4	13	172.6×	2e-25
FRS-mediated FGFR4 signaling	13	150.1×	1e-24
FGFR1c ligand binding and activation	8	141.6×	3e-15
SHC-mediated cascade:FGFR4	11	139.1×	1e-20
Phospholipase C-mediated cascade; FGFR2	9	132.8×	9e-17
PI-3K cascade:FGFR3	9	132.8×	9e-17
PI-3K cascade:FGFR2	11	127.0×	4e-20

GO biological processes:

GO term	Partners	Fold	FDR
fibroblast growth factor receptor signaling pathway	14	86.9×	2e-21
positive regulation of stem cell proliferation	5	57.2×	2e-06
positive regulation of cell division	7	51.3×	1e-08
stem cell proliferation	6	40.7×	8e-07
epidermal growth factor receptor signaling pathway	7	37.7×	8e-08
neurogenesis	8	36.2×	8e-09
cellular response to UV	5	32.1×	3e-05
regulation of cell migration	9	30.8×	2e-09

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.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for FGFR1: 1,578 ClinVar records (273 pathogenic / likely pathogenic); 6 CIViC cancer variants; 61 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,578 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	157
Likely pathogenic	116
Uncertain significance	636
Likely benign	363
Benign	82

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 273 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
224896	NM_023110.3(FGFR1):c.1638C>A (p.Asn546Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	15
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
16296	NM_023110.3(FGFR1):c.1825C>T (p.Arg609Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
50849	NM_023110.3(FGFR1):c.1042G>A (p.Gly348Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
1801171	NM_023110.3(FGFR1):c.246_247del (p.Glu84fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
225060	NM_002016.2(FLG):c.6239C>A (p.Ser2080Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
225360	NM_002016.2(FLG):c.9887C>A (p.Ser3296Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
16303	NM_023110.3(FGFR1):c.749G>A (p.Arg250Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
280412	NM_002016.2(FLG):c.1063C>T (p.Gln355Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
818057	NM_002016.2(FLG):c.1830del (p.Arg612fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1032025	NM_002016.2(FLG):c.5368C>T (p.Gln1790Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2505462	NM_023110.3(FGFR1):c.154C>T (p.Gln52Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
377227	NM_023110.3(FGFR1):c.1468G>A (p.Gly490Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1208776	NM_023110.3(FGFR1):c.962_963del (p.Lys321fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2505392	NM_023110.3(FGFR1):c.1589C>G (p.Ser530Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore FGFR1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,242):

Position(s)	Effect	Δscore	Sites
1:152315317–152315318	donor_loss	1.0000	3
1:152315478–152315479	acceptor_loss	1.0000	5
8:38413916–38413917	donor_loss	1.0000	5
8:38414024–38414025	acceptor_loss	1.0000	5
8:38414290	acceptor_loss	1.0000	2
8:38414902–38414903	acceptor_loss	1.0000	6
8:38415868–38415869	donor_loss	1.0000	5
8:38415872	donor_gain	1.0000
8:38416061–38416062	acceptor_loss	1.0000	5
8:38416071	acceptor_gain	1.0000

AlphaMissense

2,636 missense substitutions predicted likely pathogenic (of 5,386 scored), across 569 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M667	9	0.989	1.000
M535	9	0.967	0.999
M532	9	0.965	0.998
M733	9	0.948	0.998
M611	9	0.945	0.999
M217	9	0.929	0.999
M161	9	0.900	0.993
M719	9	0.895	0.995
M515	9	0.867	0.965
D641	8	1.000	1.000
D224	8	0.999	1.000
D623	8	0.999	1.000
N628	8	0.999	1.000
F489	8	0.998	1.000
D682	8	0.998	0.999
H621	8	0.997	0.999
D527	8	0.996	0.999
F642	8	0.996	1.000
D282	8	0.994	0.998
N345	8	0.992	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

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

GenCC curated gene-disease

15 curated gene-disease records:

Disease	Classification	Inheritance	Records
Hartsfield-Bixler-Demyer syndrome	Definitive	Autosomal dominant	7
hypogonadotropic hypogonadism 2 with or without anosmia	Definitive	Autosomal dominant	4
osteoglophonic dysplasia	Definitive	Autosomal dominant	6
Pfeiffer syndrome	Definitive	Autosomal dominant	3
autosomal dominant ichthyosis vulgaris	Definitive	Semidominant	4
encephalocraniocutaneous lipomatosis	Definitive	Autosomal dominant	2
Jackson-Weiss syndrome	Strong	Autosomal dominant
Pfeiffer syndrome type 1	Strong	Autosomal dominant	2
ichthyosis vulgaris	Strong	Semidominant
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

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

3 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (16 panels, 16 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

16 panels:

Panel	Rating
Cerebral malformation	green
Clefting	green
Common craniosynostosis syndromes	green
DDG2P	green
Fetal anomalies	green
Holoprosencephaly	green
Hydrocephalus	green
Hypogonadotropic hypogonadism	green
Hypogonadotropic hypogonadism (GMS)	green
IUGR and IGF abnormalities	green
Limb disorders	green
Mosaic skin disorders - Deep sequencing	green
Paediatric disorders	green
Pituitary hormone deficiency	green
Rare syndromic craniosynostosis or isolated multisuture synostosis	green
Skeletal dysplasia	green

Mondo (27): dermatitis, atopic, 2 (MONDO:0011596), ichthyosis vulgaris (MONDO:0024304), hypogonadotropic hypogonadism 2 with or without anosmia (MONDO:0007844), Pfeiffer syndrome (MONDO:0007043), Hartsfield-Bixler-Demyer syndrome (MONDO:0014196), Jackson-Weiss syndrome (MONDO:0007400), osteoglophonic dysplasia (MONDO:0008150), trigonocephaly 1 (MONDO:0008603), encephalocraniocutaneous lipomatosis (MONDO:0013074), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), hypogonadotropic hypogonadism (MONDO:0018555), rosette-forming glioneuronal tumor of fourth ventricule (MONDO:0016736), pilomyxoid astrocytoma (MONDO:0016692), lobar holoprosencephaly (MONDO:0019756), microform holoprosencephaly (MONDO:0017219), semilobar holoprosencephaly (MONDO:0700419), holoprosencephaly (MONDO:0016296), multiple epiphyseal dysplasia (MONDO:0016648), hypogonadotropic hypogonadism 11 with or without anosmia (MONDO:0013913), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), Kallmann syndrome (MONDO:0018800), autosomal dominant ichthyosis vulgaris (MONDO:0007810), septooptic dysplasia (MONDO:0008428), isolated trigonocephaly (MONDO:0018065), Pfeiffer syndrome type 1 (MONDO:0019659), tooth agenesis (MONDO:0005486), recessive X-linked ichthyosis (MONDO:0010622)

Orphanet (17): Kallmann syndrome (Orphanet:478), Pfeiffer syndrome (Orphanet:710), Hartsfield syndrome (Orphanet:2117), Jackson-Weiss syndrome (Orphanet:1540), Encephalocraniocutaneous lipomatosis (Orphanet:2396), Osteoglosphonic dysplasia (Orphanet:2645), Non-syndromic metopic craniosynostosis (Orphanet:3366), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Rosette-forming glioneuronal tumor (Orphanet:251975), Pilomyxoid astrocytoma (Orphanet:251615), Lobar holoprosencephaly (Orphanet:93924), Microform holoprosencephaly (Orphanet:280200), Semilobar holoprosencephaly (Orphanet:220386), Holoprosencephaly (Orphanet:2162), Multiple epiphyseal dysplasia (Orphanet:251), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

showing 60 of 408 phenotypes (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
HP:0000243	Trigonocephaly
HP:0000244	Brachyturricephaly
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000271	Abnormality of the face
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000336	Prominent supraorbital ridges
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000446	Narrow nasal bridge
HP:0000452	Choanal stenosis
HP:0000453	Choanal atresia
HP:0000457	Depressed nasal ridge
HP:0000458	Anosmia

GWAS associations

showing 30 of 61 associations:

Study	Trait	p-value
GCST010985_31	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	3e-82
GCST010984_49	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	5e-82
GCST007995_26	Asthma (childhood onset)	2e-65
GCST009718_16	Eczema	1e-64
GCST010042_19	Asthma	4e-39
GCST010043_158	Asthma	8e-35
GCST007798_19	Asthma	1e-30
GCST003184_5	Atopic dermatitis	6e-29
GCST009720_34	Asthma	2e-27
GCST008916_2	Asthma	5e-27
GCST007994_17	Asthma (age of onset)	8e-27
GCST008916_34	Asthma	1e-25
GCST002737_1	Atopic dermatitis	2e-25
GCST90014325_52	Asthma	7e-23
GCST009798_51	Asthma	1e-22
GCST009798_25	Asthma	2e-21
GCST005038_67	Allergic disease (asthma, hay fever or eczema)	7e-21
GCST010321_93	PR interval	3e-19
GCST007564_37	Asthma or allergic disease (pleiotropy)	5e-12
GCST001106_1	Atopic dermatitis	6e-12
GCST010796_1876	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-11
GCST007563_20	Allergic disease (asthma, hay fever or eczema)	3e-11
GCST008362_52	Birth weight	8e-11
GCST002100_1	Atopic dermatitis	9e-11
GCST003180_2	Atopic march	9e-11
GCST006661_48	Male-pattern baldness	1e-10
GCST010796_550	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-10
GCST010796_426	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-10
GCST007045_31	PR interval	5e-10
GCST006803_57	Schizophrenia	6e-10

EFO canonical traits (from GWAS)

10 canonical traits:

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

11 disease descriptors:

Descriptor	Name	Tree numbers
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
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
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.)*
C562785	Idiopathic Hypogonadotropic Hypogonadism *(supp.)*
C537559	Jackson-Weiss syndrome *(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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FGFR1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

11 curated-mechanism drugs:

Drug	Modality	Max phase
PAZOPANIB HYDROCHLORIDE	Small molecule	4
PEMIGATINIB	Small molecule	4
REGORAFENIB	Small molecule	4
SURUFATINIB	Small molecule	3
E-7090	Small molecule	2
FGFR INHIBITOR DEBIO 1347	Small molecule	2
HMPL-453	Unknown	2
LUCITANIB	Small molecule	2
TG100-801	Small molecule	2
PD-0166285 HYDROCHLORIDE	Small molecule	1
RG-1530	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FGFR1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

14 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ERDAFITINIB	Fibroblast growth factor receptor	4	4
FUTIBATINIB	Fibroblast growth factor receptor	4	4
INFIGRATINIB	Fibroblast growth factor receptor	4	4
NINTEDANIB ESYLATE	Fibroblast growth factor receptor	4	4
BRIVANIB	Fibroblast growth factor receptor	4	3
BRIVANIB ALANINATE	Fibroblast growth factor receptor	4	3
ORANTINIB	Fibroblast growth factor receptor	4	3
DERAZANTINIB	Fibroblast growth factor receptor	4	2
ENMD-981693	Fibroblast growth factor receptor	4	2
FEXAGRATINIB	Fibroblast growth factor receptor	4	2
ROGARATINIB	Fibroblast growth factor receptor	4	2
XL-999	Fibroblast growth factor receptor	4	2
CP-459632	Fibroblast growth factor receptor	4	1
LY-2874455	Fibroblast growth factor receptor	4	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 133,469 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 93 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL4297522	PEMIGATINIB	4	2,196
CHEMBL1946170	REGORAFENIB	4	13,318
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL5416410	DASATINIB	4	674
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL3545376	ERDAFITINIB	4	2,974
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3701238	FUTIBATINIB	4	874
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL1289601	LENVATINIB	4	9,224
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1448	NICLOSAMIDE	4	14,510
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL3039504	NINTEDANIB ESYLATE	4	691
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL1336	SORAFENIB	4
CHEMBL535	SUNITINIB	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL3622821	UPADACITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL4297190	SURUFATINIB	3
CHEMBL484	ADEFOVIR	3
CHEMBL483158	ALISERTIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL270995	BRIVANIB ALANINATE	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL300138	ENZASTAURIN	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL2316582	OLVEREMBATINIB	3
CHEMBL274654	ORANTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL276711	SEMAXANIB	3
CHEMBL3686884	E-7090	2
CHEMBL3907479	FGFR INHIBITOR DEBIO 1347	2
CHEMBL2220486	LUCITANIB	2
CHEMBL3545335	AG-13958	2
CHEMBL495727	AT-9283	2
CHEMBL1231124	AZD-1480	2
CHEMBL575448	BMS-754807	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2010872	CEP-11981	2
CHEMBL402548	DANUSERTIB	2
CHEMBL4297187	DERAZANTINIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL482968	ENMD-2076	2
CHEMBL3348846	FEXAGRATINIB	2
CHEMBL4514636	FISOGATINIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL5314555	LIRAFUGRATINIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL1822792	MK-2461	2

Clinical evidence (CIViC)

Drug × variant × indication, from 39 curated evidence items; also 12 prognostic, 2 functional, 1 oncogenic, 1 diagnostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 37 predictive associations by evidence level:

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	Lucitanib	Breast Cancer	Sensitivity/Response	CIViC B	EID12488 +1
FGFR1 Amplification	Erdafitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID12469
FGFR1 Amplification	Sunitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID12479
FGFR1 Amplification	Fulvestrant + Erdafitinib + Palbociclib	Breast Cancer	Sensitivity/Response	CIViC B	EID12485
FGFR1 Amplification	Everolimus + Endocrine Drug Therapy	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	Infigratinib	Breast Cancer	Resistance	CIViC B	EID1909
FGFR1 Amplification	Pemigatinib	Breast Cancer	Sensitivity/Response	CIViC C	EID12542
FGFR1 Amplification	Regorafenib	Colorectal Cancer	Sensitivity/Response	CIViC C	EID13263
FGFR1 Amplification	Infigratinib	Bladder Carcinoma	Sensitivity/Response	CIViC C	EID1911
FGFR1 Amplification	Fexagratinib	HER2 Negative Breast Cancer	Sensitivity/Response	CIViC C	EID1991
FGFR1 Amplification	Pazopanib	Breast Cancer	Sensitivity/Response	CIViC C	EID7246
FGFR1 Amplification AND MYC Overexpression	Pazopanib	Lung Squamous Cell 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	Lucitanib + Rogaratinib	Breast Cancer	Sensitivity/Response	CIViC D	EID12505
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	FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074 + Fexagratinib + Infigratinib	Sarcoma	Sensitivity/Response	CIViC D	EID2915
FGFR1 Expression	Ponatinib	Lung Cancer	Sensitivity/Response	CIViC D	EID681

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

1 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
FGFR1 Amplification	Breast Cancer		Prognostic	Tier II - Level C	Poor Outcome

CIViC curated variants (6)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Internal Duplication, Amplification (transcript amplification), Expression, Overexpression, Translocation, N546K (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

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)

3960 measured of 5632 human assays (5642 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
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
8-(3-(4-acryloylpiperazin-1-yl)propyl)-2-((cyclopropylmethyl)amino)-6-(2,6-dichloro-3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.1 nM	US-9567334: Quinolone derivatives as fibroblast growth factor receptor inhibitors
3-(2,6-Difluoro-3,5-dimethoxyphenyl)-1-methyl-1,3,4,7-tetrahydro-2H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2-one	IC50	0.12 nM
3-(2-Chloro-6-fluoro-3,5-dimethoxyphenyl)-1-methyl-1,3,4,7-tetrahydro-2H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2-one	IC50	0.17 nM
CHEMBL5177696	IC50	0.18 nM
CHEMBL5556891	IC50	0.18 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
CHEBI:63453	IC50	0.2 nM
CHEMBL3827818	IC50	0.2 nM
CHEMBL4557949	IC50	0.2 nM
CHEMBL4542061	IC50	0.2 nM
CHEMBL5189383	IC50	0.2 nM
CHEMBL5557389	IC50	0.2 nM
CHEMBL5558932	IC50	0.22 nM
CHEMBL5178408	IC50	0.23 nM
CHEMBL5187998	IC50	0.24 nM
CHEMBL5181688	IC50	0.24 nM
Balversa	IC50	0.25 nM
CHEMBL5186645	IC50	0.25 nM
CHEMBL5505835	IC50	0.25 nM
CHEMBL5202576	IC50	0.26 nM
CHEMBL5186714	IC50	0.27 nM
CHEMBL4100258	IC50	0.28 nM
CHEMBL5182360	IC50	0.28 nM
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
N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	IC50	0.3 nM	US-10562900: Indazole compounds as FGFR kinase inhibitor, preparation and use thereof
CHEMBL3828009	IC50	0.3 nM
CHEMBL3827492	IC50	0.3 nM
CHEMBL4461734	IC50	0.3 nM
CHEMBL4447575	IC50	0.3 nM
CHEMBL4447359	IC50	0.3 nM
CHEMBL4553127	IC50	0.3 nM
[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
CHEMBL5191744	IC50	0.32 nM
CHEMBL5556836	IC50	0.33 nM
CHEMBL5505810	IC50	0.34 nM
CHEMBL5206740	IC50	0.35 nM
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
CHEMBL5542848	IC50	0.36 nM
CHEMBL5523440	IC50	0.36 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
CHEMBL5173348	IC50	0.37 nM
CHEMBL5170945	IC50	0.37 nM
CHEMBL5198510	IC50	0.38 nM
CHEMBL5202912	IC50	0.38 nM
8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(isopropylamino)pyrido[2,3-d]pyrimidin-7(8H)-one	IC50	0.4 nM	US-9567334: Quinolone derivatives as fibroblast growth factor receptor inhibitors
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	0.4 nM	US-9567334: Quinolone derivatives as fibroblast growth factor receptor inhibitors

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

2047 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
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
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-(1-piperidin-4-ylpyrazol-4-yl)-1,3,5-triazin-2-amine	1880021: Inhibition of wild-type FGFR1 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression, decreases response to substance, decreases expression, increases reaction, decreases phosphorylation	6
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, increases mutagenesis	5
SU 5402	decreases activity	4
ponatinib	decreases activity, decreases phosphorylation	4
Particulate Matter	increases abundance, increases expression, affects expression	4
Valproic Acid	increases methylation, affects expression, decreases expression, increases expression	3
futibatinib	decreases activity	2
bisphenol A	increases expression, decreases methylation	2
PD 173074	increases expression, decreases expression, increases reaction, decreases activity, decreases phosphorylation (+1 more)	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	affects cotreatment, decreases methylation, decreases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects cotreatment, affects expression, increases abundance, increases expression	2
Hydrogen Peroxide	affects binding, increases reaction, decreases expression	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	decreases expression, increases abundance	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

23 cell lines: 20 cancer cell line, 2 transformed cell line, 1 factor-dependent 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 160 trials:

NCT	Phase	Status	Title
NCT00140413	Phase 4	COMPLETED	Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
NCT00328926	Phase 4	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	Phase 4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	Phase 4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	Phase 4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	Phase 4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	Phase 4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	Phase 4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	Phase 4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	Phase 4	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	Phase 4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	Phase 4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	Phase 4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	Phase 4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00722436	Phase 4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	Phase 4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT03975829	Phase 4	ACTIVE_NOT_RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT06760546	Phase 3	RECRUITING	A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
NCT00467870	Phase 3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	Phase 3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	Phase 3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	Phase 3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	Phase 3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	Phase 3	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	Phase 3	COMPLETED	An Extension Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01739595	Phase 3	COMPLETED	Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
NCT01993212	Phase 3	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	Phase 3	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	Phase 3	COMPLETED	Bioequivalence Study of Test and Reference Testosterone Topical Gel, 1.62% Metered Pump in Testosterone Deficient Adult Male Subjects Under Fasting Conditions
NCT03019575	Phase 3	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	Phase 3	NOT_YET_RECRUITING	To Evaluate Recombinant Human Follicle Stimulating Hormone-CTP Fusion Protein Injection or Placebo Combined With Chorionic Gonadotropin for Injection
NCT00827151	Phase 3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00193661	Phase 2	COMPLETED	Observation Study of T-Gel (1%) in Treatment of Adolescent Boys With Hypogonadism
NCT00383656	Phase 2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00697814	Phase 2	COMPLETED	Clomiphene in Males With Prolactinomas and Persistent Hypogonadism
NCT00706719	Phase 2	COMPLETED	To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone
NCT00911586	Phase 2	COMPLETED	Pharmacokinetic Study to Determine Time to Steady-state
NCT01155518	Phase 2	TERMINATED	Hypogonadism in Young Men With Type 2 Diabetes
NCT01191320	Phase 2	COMPLETED	Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus
NCT01270841	Phase 2	COMPLETED	Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism
NCT01386606	Phase 2	COMPLETED	The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone)
NCT01894308	Phase 2	NOT_YET_RECRUITING	A Dose Ranging Study to Examine TDS-Testosterone 5%
NCT02369796	Phase 2	TERMINATED	A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism
NCT02443090	Phase 2	UNKNOWN	Safety and Efficacy Study of Oral Fispemifene for the Treatment of Sexual Dysfunction in Hypogonadal Men
NCT02651688	Phase 2	COMPLETED	A Multi-Center Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Body Composition and Metabolic Parameters With Diet and Exercise in Conjunction With Treatment With 12.5 mg or 25 mg Enclomiphene
NCT02730169	Phase 2	COMPLETED	Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism
NCT02733133	Phase 2	NOT_YET_RECRUITING	Product Transference Study of Testagen™ TDS®-Testosterone
NCT02908074	Phase 2	COMPLETED	A 6 Month Safety Extension Study of MBGS205
NCT03245827	Phase 2	TERMINATED	Hypogonadotropic Hypogonadism in Obese Young Males
NCT04189133	Phase 2	UNKNOWN	Rec-LH PD and Safety Profile in Hypogonadotropic Hypogonadism Men
NCT04648969	Phase 2	COMPLETED	Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism
NCT05896293	Phase 2	RECRUITING	Kisspeptin Administration Subcutaneously to Patients With IHH
NCT07224438	Phase 2	RECRUITING	Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea
NCT00064987	Phase 2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT03173547	Phase 2	COMPLETED	A Six Week Topical Cream Study for Subjects With Ichthyosis Vulgaris
NCT00130117	Phase 2	COMPLETED	Study of Leptin for the Treatment of Hypothalamic Amenorrhea
NCT00152282	Phase 2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Asoprisnil and Estrogen Administration to Postmenopausal Women
NCT00196391	Phase 2	COMPLETED	A Trial to Evaluate DR-2021 in Women With Secondary Amenorrhea
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT02229968	Phase 2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FGFR1 across ~30M SureChEMBL compounds — explore on Sugi Predict.