FGFR2

Summary

FGFR2 (fibroblast growth factor receptor 2, HGNC:3689) is a protein-coding gene on chromosome 10q26.13, encoding Fibroblast growth factor receptor 2 (P21802). Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. In precision oncology, FGFR2 Mutation OR FGFR2::v Fusion OR FGFR2::? Fusion confers sensitivity to Erdafitinib in Transitional Cell Carcinoma (CIViC Level A); 12 further curated variant–drug associations are listed below.

The protein encoded by this gene is a member of the fibroblast growth factor receptor 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 is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 2263 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Apert syndrome (Definitive, ClinGen) — +15 more curated relationships
• GWAS associations: 63
• Clinical variants (ClinVar): 955 total — 74 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 369
• Druggable target: yes — 59 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 13 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• MANE Select transcript: NM_000141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3689
Approved symbol	FGFR2
Name	fibroblast growth factor receptor 2
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	CEK3, TK14, TK25, ECT1, K-SAM, CD332
Ensembl gene	ENSG00000066468
Ensembl biotype	protein_coding
OMIM	176943
Entrez	2263

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 27 protein_coding, 8 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 non_stop_decay

ENST00000336553, ENST00000346997, ENST00000351936, ENST00000356226, ENST00000357555, ENST00000358487, ENST00000359354, ENST00000360144, ENST00000369056, ENST00000369058, ENST00000369059, ENST00000369060, ENST00000369061, ENST00000429361, ENST00000457416, ENST00000463870, ENST00000467584, ENST00000478859, ENST00000490349, ENST00000491111, ENST00000491475, ENST00000604236, ENST00000611527, ENST00000613048, ENST00000613324, ENST00000636922, ENST00000638709, ENST00000682296, ENST00000682400, ENST00000682550, ENST00000682772, ENST00000682904, ENST00000683029, ENST00000683035, ENST00000683211, ENST00000683250, ENST00000683418, ENST00000683678, ENST00000683885, ENST00000684153, ENST00000684516, ENST00000937092, ENST00000937093

RefSeq mRNA: 12 — MANE Select: NM_000141 NM_000141, NM_001144913, NM_001144914, NM_001144915, NM_001144916, NM_001144917, NM_001144918, NM_001144919, NM_001320654, NM_001320658, NM_022970, NM_023029

CCDS: CCDS31298, CCDS44485, CCDS44486, CCDS44487, CCDS44488, CCDS44489, CCDS53584, CCDS73210, CCDS7620, CCDS81514, CCDS81515

Canonical transcript exons

ENST00000358487 — 18 exons

Exon	Start	End
ENSE00001816393	121597962	121598444
ENSE00001847306	121478332	121480021
ENSE00003486661	121498495	121498605
ENSE00003488412	121565438	121565704
ENSE00003525972	121496532	121496722
ENSE00003530900	121519979	121520169
ENSE00003547346	121487354	121487424
ENSE00003553724	121503790	121503941
ENSE00003567716	121593709	121593967
ENSE00003589679	121551290	121551459
ENSE00003608712	121517319	121517463
ENSE00003618465	121487991	121488113
ENSE00003629514	121515117	121515319
ENSE00003631185	121500826	121500947
ENSE00003637083	121564502	121564579
ENSE00003680367	121485395	121485532
ENSE00003681829	121538592	121538715
ENSE00003790431	121483698	121483803

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 9.7520 / max 1395.1915, expressed in 740 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111737	6.9824	708
111736	0.9276	307
111740	0.8944	180
111739	0.3173	74
111741	0.2138	84
111735	0.1342	68
111738	0.1126	46
111727	0.0628	21
111724	0.0619	23
111731	0.0450	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.50	gold quality
spinal cord	UBERON:0002240	99.28	gold quality
corpus callosum	UBERON:0002336	98.76	gold quality
inferior olivary complex	UBERON:0002127	98.72	gold quality
ventricular zone	UBERON:0003053	98.43	gold quality
parotid gland	UBERON:0001831	98.21	gold quality
inferior vagus X ganglion	UBERON:0005363	97.85	gold quality
lateral globus pallidus	UBERON:0002476	97.76	gold quality
subthalamic nucleus	UBERON:0001906	97.57	gold quality
substantia nigra	UBERON:0002038	97.52	gold quality
midbrain	UBERON:0001891	97.38	gold quality
medulla oblongata	UBERON:0001896	97.09	gold quality
upper leg skin	UBERON:0004262	97.07	gold quality
skin of hip	UBERON:0001554	96.73	gold quality
putamen	UBERON:0001874	96.68	gold quality
pigmented layer of retina	UBERON:0001782	96.61	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.43	gold quality
pons	UBERON:0000988	96.42	gold quality
cartilage tissue	UBERON:0002418	96.41	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.31	gold quality
globus pallidus	UBERON:0001875	96.21	gold quality
CA1 field of hippocampus	UBERON:0003881	96.19	gold quality
Ammon’s horn	UBERON:0001954	96.03	gold quality
superior vestibular nucleus	UBERON:0007227	95.96	gold quality
upper arm skin	UBERON:0004263	95.93	gold quality
cranial nerve II	UBERON:0000941	95.75	gold quality
medial globus pallidus	UBERON:0002477	95.75	gold quality
postcentral gyrus	UBERON:0002581	95.75	gold quality
amygdala	UBERON:0001876	95.63	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	50.57
E-MTAB-10287	yes	44.45
E-MTAB-10553	yes	22.10
E-ANND-3	yes	20.96
E-HCAD-9	yes	8.44
E-GEOD-109979	no	115.69
E-MTAB-6379	no	1.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PPARG	Activation

Upstream regulators (CollecTRI, top): CEBPB, E2F1, E2F2, E2F3, E2F4, E2F5, HOXC6, NANOGP8, POU2F1, RUNX2, TCF3, TWIST1

miRNA regulators (miRDB)

186 targeting FGFR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4745-5P	99.98	65.95	1028
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-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• Associated with Pfeiffer syndrome (PMID:11556600)
• 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)
• distribution in normal endocrine cells and related tumors of the gastroenteropancreatic system; immunoreactive in gastric and duodenal G cells, pancreatic B cells, and rectal EC cells (PMID:11759058)
• genomic screening reveals a wide spectrum of mutations in patients with syndromic craniosynostosis (PMID:11781872)
• genomic sequence and variations (SNPs) (PMID:11856867)
• KGF induced proliferation but did not cause significant differentiation of 3 hematopoietic cell lines and bone marrow cells transduced with human K-sam. (PMID:11937263)
• role of Ser351Cys mutation in causing craniosynostosis and sacral appendage (PMID:12072807)
• details of the endocytic pathway followed by the keratinocyte growth factor receptor following activation by KGF binding (PMID:12122441)
• Craniofacial dysostosis is associated with mutations of FGFR2 and is characterized by premature fusion of cranial sutures. (PMID:12162872)
• FGFR2 has a role in controlling normal and premature cranial ossification in humans [review] (PMID:12168799)
• 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)
• a nonsequence-specific double stranded RNA stem constitutes a functional element required for FGFR2 splicing (PMID:12393912)
• A novel splice variant of FGFR2 (FGFR2AT-I) arising from skipping exons 7-10 was able to bind FGF1, FGF2, and FGF7, leading to loss of ligand binding specificity and increased AKT and MAPK activation, conferring a survival advantage. (PMID:12482414)
• PAK4 interacts with KGF receptor and mediate anti-apoptosis effects of KGF on epithelial cells. (PMID:12529371)
• FGFR2b is alternatively spliced and is activated by FGF7 and FGF10 (PMID:12591959)
• KGFR was localized in the vascular smoooth muscle cells in normal human coronary arteries and in the thickened intima of atherosclerotic arteries. (PMID:12608893)
• mRNA splicing of fibroblast growth factor receptor 2 is associated with Chondrosarcoma (PMID:12618336)
• This gene is expressed on chromosome 10p26. (PMID:12684685)
• Data show that the HTPAPL-WDR11-FGFR2 locus was more susceptible to recombination than to nucleotide substitution. (PMID:12684693)
• physical association of p63alpha and ABBP1 led to a specific shift of FGFR-2 alternative splicing toward the K-SAM isoform essential for epithelial differentiation (PMID:12692135)
• proposed that the FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise (PMID:12893942)
• Activation of iFGFR1, but not iFGFR2, led to strong up-regulation of osteopontin in prostate adenocarcinoma. (PMID:14559809)
• regulated splicing of fibroblast growth factor receptor-2 transcripts leads to tissue-specific expression of distinct receptor isoforms (PMID:14624010)
• KGFR was prominently localized in proliferating reserve cells and squamous metaplastic reserve cells adjacent to cancer cells. In contrast, KGFR was not detected in cervical ductal cells in cancer or non-cancer cervical tissues. (PMID:15069536)
• FGFR2 activation induces osteoblast differentiation by Cbl-mediated degradation of Lyn and Fyn (PMID:15190072)
• A point mutation in fibroblast growth factor receptor 2 (FGFR2) was identified that had previously been seen only in sporadic cases of Crouzon syndrome. (PMID:15206560)
• Elevated Apert syndrome mutant FGFR2b signaling may account for the dermatological manifestations of Apert syndrome (PMID:15282208)
• Osteocalcin mRNA was down-regulated in Apert osteoblasts carrying the FGFR2 P253R mutation, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. (PMID:15389579)
• inhibits the growth of bladder carcinoma cells by reducing IGF-II levels via its carboxy-terminal domain, independent of its tyrosine kinase activity (PMID:15516981)
• Missense substitution in FGFR2 is associated with Crouzon syndrome (PMID:15523492)
• FGFR2 is a transforming oncogene in human mammary epithelial cells when expressed to levels similar to that found in breast cancer cells with FGFR2 gene amplification. (PMID:15561780)
• in-frame insertion in exon 8 reported in a child with Crouzon’s syndrome, tracheal anomalies, and a tail (PMID:15602758)
• In ‘undifferentiated’ neurospheres of embryonic brain and spinal cord, transcripts from FGFR1 and FGFR2 were consistently detected. (PMID:15618886)
• Review. Advances in understanding the molecular basis for Apert syndrome through clinical genetic, biochemical, & structural approaches of FGFR2 are reviewed. (PMID:15622262)
• Data validate the symmetric two-end model of fibroblast growth factor (FGF) receptor (FGFR) dimerization and FGF binding and argue against the asymmetric model of FGFR dimerization. (PMID:15632068)
• These findings indicate that KGFR may play important roles in the differentiation of normal colorectal epithelial cells and establishment of the well-differentiated histological type of colorectal cancer cells. (PMID:15643506)
• the alpha5 integrin subunit has a role in the induction of apoptosis triggered by FGFR2 activation in osteoblasts, and a Cbl-dependent mechanism is involved in the coordinated regulation of cell apoptosis induced by alpha5 integrin degradation (PMID:15728256)
• Alleleic loss at 10q26 in osteosarcoma is reported in the region of FGFR2. (PMID:15796961)
• provides genetic and biochemical evidence for a role of Fgfr2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in Saethre-Chotzen syndrome (PMID:15829502)
• FGFR2 mutations attain high levels in sperm because they encode proteins with gain-of-function properties, favoring clonal expansion of mutant spermatogonial cells. (PMID:15840724)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgfr2	ENSDARG00000058115
mus_musculus	Fgfr2	ENSMUSG00000030849
rattus_norvegicus	Fgfr2	ENSRNOG00000016374

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Fibroblast growth factor receptor 2 — P21802 (reviewed: P21802)

Alternative names: K-sam, Keratinocyte growth factor receptor

All UniProt accessions (17): P21802, A0A087WY21, A0A087X2D1, A0A0A0MR25, A0A141AXF1, A0A1B0GWF4, A0A1W2PQT9, A0A5S6RJB7, A0A804HI10, A0A804HI76, A0A804HIH8, D2CGD1, E7EVR7, H7BXU9, H7C265, S4R381, S4R3B2

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 cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.

Subunit / interactions. Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (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. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PLCG1, GRB2 and PAK4. Interacts with FLRT2.

Subcellular location. Cell membrane. Golgi apparatus. Cytoplasmic vesicle Cell membrane Cell membrane Secreted Secreted.

Post-translational modifications. Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1. N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus. Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.

Disease relevance. Crouzon syndrome (CS) [MIM:123500] An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. 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. Apert syndrome (APRS) [MIM:101200] A syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations. The disease is caused by variants affecting the gene represented in this entry. 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. Beare-Stevenson cutis gyrata syndrome (BSTVS) [MIM:123790] An autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. The disease is caused by variants affecting the gene represented in this entry. Familial scaphocephaly syndrome (FSPC) [MIM:609579] An autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation. The disease is caused by variants affecting the gene represented in this entry. Lacrimo-auriculo-dento-digital syndrome 1 (LADD1) [MIM:149730] A form of lacrimo-auriculo-dento-digital syndrome, an autosomal dominant disease characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed. The disease is caused by variants affecting the gene represented in this entry. Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2) [MIM:207410] A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported. The disease is caused by variants affecting the gene represented in this entry. Bent bone dysplasia syndrome 1 (BBDS1) [MIM:614592] A perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia. The disease is caused by variants affecting the gene represented in this entry. Saethre-Chotzen syndrome (SCS) [MIM:101400] A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly. 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 autophosphorylation on tyrosine residues. Inhibited by ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation.

Domain organisation. The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity.

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

Isoforms (17)

UniProt ID	Names	Canonical?
P21802-1	1, BEK, FGFR2IIIc	yes
P21802-2	2, Short
P21802-3	3, BFR-1, FGFR2IIIb, KGFR
P21802-4	4, K-sam
P21802-5	5, K-sam-I, BEK, IgIIIc
P21802-6	6, K-sam-IIC2
P21802-8	7, K-sam-IIC3
P21802-14	8, K-sam-IV, Soluble KGFR
P21802-15	9, K-sam-III
P21802-16	10, TK14
P21802-17	11
P21802-18	12, K-sam-IIC1, KGFR, IgIIIb
P21802-19	13, Soluble KGFR
P21802-20	14
P21802-21	15
P21802-22	16
P21802-23	17

RefSeq proteins (12): NP_000132, NP_001138385, NP_001138386, NP_001138387, NP_001138388, NP_001138389, NP_001138390, NP_001138391, NP_001307583, NP_001307587, NP_075259, NP_075418 (=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
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016248	FGF_rcpt_fam	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF07679, PF07714, PF13927

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (198 total): sequence variant 74, strand 34, helix 20, splice variant 19, turn 8, glycosylation site 8, modified residue 7, mutagenesis site 5, binding site 4, domain 4, sequence conflict 3, disulfide bond 3, region of interest 2, topological domain 2, signal peptide 1, chain 1, compositionally biased region 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

63 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
10OU	X-RAY DIFFRACTION	1.77
2PVF	X-RAY DIFFRACTION	1.8
3B2T	X-RAY DIFFRACTION	1.8
4J99	X-RAY DIFFRACTION	1.85
10OO	X-RAY DIFFRACTION	1.85
5UGL	X-RAY DIFFRACTION	1.86
3CAF	X-RAY DIFFRACTION	1.96
10OQ	X-RAY DIFFRACTION	1.98
9U7S	X-RAY DIFFRACTION	1.99
3CLY	X-RAY DIFFRACTION	2
8W3D	X-RAY DIFFRACTION	2.04
5UI0	X-RAY DIFFRACTION	2.05
3OJM	X-RAY DIFFRACTION	2.1
3RI1	X-RAY DIFFRACTION	2.1
1EV2	X-RAY DIFFRACTION	2.2
2PVY	X-RAY DIFFRACTION	2.2
3DAR	X-RAY DIFFRACTION	2.2
3OJ2	X-RAY DIFFRACTION	2.2
9U7E	X-RAY DIFFRACTION	2.2
7KIA	X-RAY DIFFRACTION	2.22
8W3B	X-RAY DIFFRACTION	2.23
8SWE	X-RAY DIFFRACTION	2.24
9VLM	X-RAY DIFFRACTION	2.26
2FDB	X-RAY DIFFRACTION	2.28
7OZY	X-RAY DIFFRACTION	2.28
6LVK	X-RAY DIFFRACTION	2.29
4J96	X-RAY DIFFRACTION	2.3
1IIL	X-RAY DIFFRACTION	2.3
2PY3	X-RAY DIFFRACTION	2.3
4J98	X-RAY DIFFRACTION	2.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21802-F1	74.33	0.37

Antibody-complex structures (SAbDab): 1 — 4WV1

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 (1): 626 (proton acceptor)

Ligand- & substrate-binding residues (4): 487–495; 517; 565–567; 571

Post-translational modifications (7): 466, 586, 588, 656, 657, 769, 780

Disulfide bonds (3): 62–107, 179–231, 278–342

Glycosylation sites (8): 83, 123, 228, 241, 265, 297, 318, 331

Mutagenesis-validated functional residues (5):

Position	Phenotype
265	reduced n-glycosylation. reduced expression at the cell surface.
549	constitutive kinase activity.
565	constitutive kinase activity.
656–657	loss of kinase activity.
769	increases fibroblast proliferation. decreases phosphorylation of plcg1 and frs2. decreases activation of map kinases.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-2023837	Signaling by FGFR2 amplification mutants
R-HSA-2033519	Activated point mutants of FGFR2
R-HSA-5655253	Signaling by FGFR2 in disease
R-HSA-8851708	Signaling by FGFR2 IIIa TM
R-HSA-8853333	Signaling by FGFR2 fusions
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-190375	FGFR2c ligand binding and activation
R-HSA-190377	FGFR2b ligand binding and activation
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654221	Phospholipase C-mediated cascade; FGFR2
R-HSA-5654695	PI-3K cascade:FGFR2
R-HSA-5654699	SHC-mediated cascade:FGFR2
R-HSA-5654700	FRS-mediated FGFR2 signaling
R-HSA-5654727	Negative regulation of FGFR2 signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-6803529	FGFR2 alternative splicing

MSigDB gene sets: 1323 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_ETHANOL, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, TAATAAT_MIR126, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT

GO Biological Process (104): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), ureteric bud development (GO:0001657), in utero embryonic development (GO:0001701), epithelial to mesenchymal transition (GO:0001837), positive regulation of mesenchymal cell proliferation (GO:0002053), outflow tract septum morphogenesis (GO:0003148), membranous septum morphogenesis (GO:0003149), endochondral bone growth (GO:0003416), apoptotic process (GO:0006915), cell-cell signaling (GO:0007267), axonogenesis (GO:0007409), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), regulation of smoothened signaling pathway (GO:0008589), post-embryonic development (GO:0009791), embryonic pattern specification (GO:0009880), animal organ morphogenesis (GO:0009887), positive regulation of phospholipase activity (GO:0010518), negative regulation of keratinocyte proliferation (GO:0010839), morphogenesis of embryonic epithelium (GO:0016331), peptidyl-tyrosine phosphorylation (GO:0018108), orbitofrontal cortex development (GO:0021769), ventricular zone neuroblast division (GO:0021847), pyramidal neuron development (GO:0021860), gland morphogenesis (GO:0022612), positive regulation of Wnt signaling pathway (GO:0030177), bone mineralization (GO:0030282), lung development (GO:0030324), epithelial cell differentiation (GO:0030855), midbrain development (GO:0030901), otic vesicle formation (GO:0030916), hair follicle morphogenesis (GO:0031069), response to lipopolysaccharide (GO:0032496), lacrimal gland development (GO:0032808), regulation of osteoblast proliferation (GO:0033688), organ growth (GO:0035265), fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell (GO:0035602), fibroblast growth factor receptor signaling pathway involved in hemopoiesis (GO:0035603), fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow (GO:0035604)

GO Molecular Function (13): 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), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), 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 (11): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell cortex (GO:0005938), cell surface (GO:0009986), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), signaling receptor complex (GO:0043235), excitatory synapse (GO:0060076)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
FGFR2 mutant receptor activation	4
Downstream signaling of activated FGFR2	4
FGFR2 ligand binding and activation	2
Signaling by FGFR2	2
Signaling by FGFR in disease	1
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
anatomical structure morphogenesis	2
intracellular membrane-bounded organelle	2
cell periphery	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
mesonephric tubule development	1
chordate embryonic development	1
mesenchymal cell differentiation	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
ventricular septum morphogenesis	1
bone growth	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	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
smoothened signaling pathway	1
regulation of signal transduction	1
multicellular organism development	1
multicellular organismal process	1
pattern specification process	1
embryo development	1
animal organ development	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

123 interactions, top by confidence:

A	B	Type	Score
FGFR2	FGF2	psi-mi:“MI:0407”(direct interaction)	0.780
FGF2	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.780
GRB2	FGFR2	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
GRB2	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.740
FGFR2	GRB2	psi-mi:“MI:0407”(direct interaction)	0.740
	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.680
FGFR2	FGF1	psi-mi:“MI:0407”(direct interaction)	0.670
FGF1	FGFR2	psi-mi:“MI:2364”(proximity)	0.670
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
RPS6KA3	ROCK2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
FGFR2	FGFR1	psi-mi:“MI:0915”(physical association)	0.620
FGF10	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.570
FGF10	FGFR2	psi-mi:“MI:2364”(proximity)	0.570
FGFR2	FCER2	psi-mi:“MI:0407”(direct interaction)	0.560
FCER2	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
FAM171B	FAM171A2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (326): FGFR2 (Affinity Capture-MS), FGFR2 (Affinity Capture-MS), BEX1 (Two-hybrid), BEX2 (Two-hybrid), ERRFI1 (Two-hybrid), GLCE (Two-hybrid), HOXC6 (Two-hybrid), MTA3 (Two-hybrid), PDLIM2 (Two-hybrid), RASL10B (Two-hybrid), RHOBTB2 (Two-hybrid), S100A14 (Two-hybrid), TFF1 (Two-hybrid), FGF1 (Co-localization), FGF10 (Co-localization)

ESM2 similar proteins: A0A6I8TCE0, B0X4T2, F1NY98, O00533, O35158, O55005, O60469, O89026, O97394, P12960, P14781, P16092, P17790, P18460, P18461, P21802, P21803, P28685, P29074, P35331, P35832, P57097, P70232, P97686, Q12860, Q12866, Q28106, Q32MD9, Q3UH53, Q4KMG0, Q60805, Q61851, Q63198, Q7Z5N4, Q7ZXX1, Q810U4, Q8AV58, Q8AXZ4, Q8JG38, Q8VHZ8

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

SIGNOR signaling

30 interactions.

A	Effect	B	Mechanism
BGJ-398	down-regulates	FGFR2	“chemical inhibition”
“Brivanib alaninate”	down-regulates	FGFR2	“chemical inhibition”
FGFR2	unknown	PTEN	phosphorylation
FGFR2	up-regulates	GRB2	phosphorylation
PRKCE	up-regulates	FGFR2	phosphorylation
FGFR2	“up-regulates quantity by expression”	PPARG	“transcriptional regulation”
regorafenib	“down-regulates activity”	FGFR2	“chemical inhibition”
ponatinib	“down-regulates activity”	FGFR2	“chemical inhibition”
ADAM9	“down-regulates quantity by destabilization”	FGFR2	cleavage
FGFR2	“up-regulates activity”	FGFR2	phosphorylation
PTPN11	“down-regulates activity”	FGFR2	dephosphorylation
FGF5	up-regulates	FGFR2	binding
FGF10	up-regulates	FGFR2	binding
FGF17	up-regulates	FGFR2	binding
FGF18	up-regulates	FGFR2	binding
FGF3	up-regulates	FGFR2	binding
FGF4	up-regulates	FGFR2	binding
FGF6	up-regulates	FGFR2	binding
FGF1	up-regulates	FGFR2	binding
FGF2	up-regulates	FGFR2	binding
FGFR2	up-regulates	MAP2K1
FGFR2	up-regulates	MEK1/2
FGFR2	“up-regulates activity”	FRS2	phosphorylation
nintedanib	“down-regulates activity”	FGFR2	“chemical inhibition”
“2-Hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylic acid”	“down-regulates activity”	FGFR2	“chemical inhibition”
NANOGP8	“down-regulates quantity by repression”	FGFR2	“transcriptional regulation”
FGFR2	“up-regulates activity”	GLO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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: FGFR1	8	86.7×	1e-12
FGFR1c ligand binding and activation	7	86.0×	4e-11
PI-3K cascade:FGFR1	9	75.3×	3e-13
Phospholipase C-mediated cascade; FGFR2	7	71.6×	1e-10
PI-3K cascade:FGFR3	7	71.6×	1e-10
FRS-mediated FGFR1 signaling	9	66.3×	7e-13
Activated point mutants of FGFR2	6	65.0×	5e-09
SHC-mediated cascade:FGFR1	8	64.1×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
fibroblast growth factor receptor signaling pathway	10	30.4×	8e-10
positive regulation of stem cell proliferation	5	28.0×	2e-04
cellular response to epidermal growth factor stimulus	5	16.9×	1e-03
neurogenesis	7	15.5×	1e-04
protein dephosphorylation	6	14.2×	4e-04
epidermal growth factor receptor signaling pathway	5	13.2×	2e-03
regulation of cell migration	6	10.1×	2e-03
cytokine-mediated signaling pathway	6	8.3×	4e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

The FGFR proteins are involved in a wide array of pathways known to play a signficant role in cancer. Activation of these receptors can lead to activation of the RAS-MAPK pathway and the PI3K-AKT pathway, among others. The mechanisms by which FGFR can be misregulated vary between cancers. Amplification of the receptors has been observed in lung and breast cancers, coding mutations and deletions have been seen in many cancers, and more recently, FGFR fusions that lead to pathway actiation have been demonstrated to have oncogenic potential across multiple cancer types. The targeted therapeutics ponatinib, dovitinib and pazopanib have seen success in treating over-active FGFR signalling, prompting use of diagnostic sequencing targeting the FGFR genes, especially in lung cancer patients.

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — BRCA, CHOL, LUSC, SACA, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	74
Likely pathogenic	37
Uncertain significance	386
Likely benign	248
Benign	77

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1060632	NM_000141.5(FGFR2):c.962A>T (p.Asp321Val)	Pathogenic
1073828	NC_000010.10:g.(?123276813)(123276997_?)del	Pathogenic
1076383	NM_000141.5(FGFR2):c.1030G>C (p.Ala344Pro)	Pathogenic
1322899	NM_000141.5(FGFR2):c.940-1G>T	Pathogenic
13265	NM_000141.5(FGFR2):c.1061C>G (p.Ser354Cys)	Pathogenic
13266	NM_000141.5(FGFR2):c.1024T>C (p.Cys342Arg)	Pathogenic
13267	NM_000141.5(FGFR2):c.1024T>A (p.Cys342Ser)	Pathogenic
13268	NM_000141.5(FGFR2):c.1032G>A (p.Ala344=)	Pathogenic
13269	NM_000141.5(FGFR2):c.1031C>G (p.Ala344Gly)	Pathogenic
13272	NM_000141.5(FGFR2):c.755C>G (p.Ser252Trp)	Pathogenic
13274	NM_000141.5(FGFR2):c.1021A>C (p.Thr341Pro)	Pathogenic
13275	NM_000141.5(FGFR2):c.1026C>G (p.Cys342Trp)	Pathogenic
13276	NM_000141.5(FGFR2):c.866A>C (p.Gln289Pro)	Pathogenic
13278	NM_000141.5(FGFR2):c.1115C>G (p.Ser372Cys)	Pathogenic
13280	NM_000141.5(FGFR2):c.755_757delinsTCT (p.Ser252_Pro253delinsPheSer)	Pathogenic
13281	NM_000141.5(FGFR2):c.870G>C (p.Trp290Cys)	Pathogenic
13283	NM_000141.5(FGFR2):c.868T>C (p.Trp290Arg)	Pathogenic
13284	NM_000141.5(FGFR2):c.868T>G (p.Trp290Gly)	Pathogenic
13285	NM_000141.5(FGFR2):c.804_809del (p.Val269_Val270del)	Pathogenic
13286	NM_000141.5(FGFR2):c.1052C>G (p.Ser351Cys)	Pathogenic
13287	NM_000141.5:c.1040_1041ins[N[360];1026_1040]	Pathogenic
13289	NM_000141.5(FGFR2):c.943G>T (p.Ala315Ser)	Pathogenic
13290	NM_000141.5(FGFR2):c.799T>C (p.Ser267Pro)	Pathogenic
13291	NM_000141.5(FGFR2):c.940-1G>A	Pathogenic
13292	NM_000141.5(FGFR2):c.940-3_946delinsACC	Pathogenic
13293	NM_000141.5(FGFR2):c.870G>T (p.Trp290Cys)	Pathogenic
13296	NM_000141.5(FGFR2):c.1942G>A (p.Ala648Thr)	Pathogenic
13297	NM_000141.5(FGFR2):c.1947_1949del (p.Arg649_Asp650delinsSer)	Pathogenic
13298	NM_000141.5(FGFR2):c.1882G>A (p.Ala628Thr)	Pathogenic
13299	NM_000141.5(FGFR2):c.1084+3A>G	Pathogenic

SpliceAI

3944 predictions. Top by Δscore:

Variant	Effect	Δscore
10:121483692:TCTTA:T	donor_loss	1.0000
10:121483693:CTTAC:C	donor_loss	1.0000
10:121483694:TTACC:T	donor_loss	1.0000
10:121483695:TACCT:T	donor_loss	1.0000
10:121483696:A:AC	donor_gain	1.0000
10:121483696:A:C	donor_loss	1.0000
10:121483697:C:CC	donor_gain	1.0000
10:121483697:C:CT	donor_loss	1.0000
10:121483697:CCT:C	donor_gain	1.0000
10:121483697:CCTCA:C	donor_gain	1.0000
10:121483800:GTACC:G	acceptor_loss	1.0000
10:121483801:TACC:T	acceptor_loss	1.0000
10:121483802:ACC:A	acceptor_loss	1.0000
10:121483804:C:CA	acceptor_loss	1.0000
10:121483805:T:A	acceptor_loss	1.0000
10:121485393:A:AC	donor_gain	1.0000
10:121485394:C:CC	donor_gain	1.0000
10:121485394:CAGTT:C	donor_gain	1.0000
10:121485437:T:TA	donor_gain	1.0000
10:121485529:CCAG:C	acceptor_gain	1.0000
10:121485530:CAG:C	acceptor_gain	1.0000
10:121485530:CAGC:C	acceptor_gain	1.0000
10:121485531:AG:A	acceptor_gain	1.0000
10:121485533:C:CC	acceptor_gain	1.0000
10:121487353:CA:C	donor_gain	1.0000
10:121487984:GACTT:G	donor_loss	1.0000
10:121487985:ACTTA:A	donor_loss	1.0000
10:121487986:CTT:C	donor_loss	1.0000
10:121487987:TTAC:T	donor_loss	1.0000
10:121487989:A:AC	donor_gain	1.0000

AlphaMissense

5405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:121483758:T:A	R747S	1.000
10:121483758:T:G	R747S	1.000
10:121483781:A:G	W740R	1.000
10:121483781:A:T	W740R	1.000
10:121485443:A:G	L716P	1.000
10:121485446:A:G	L715P	1.000
10:121485455:A:G	L712P	1.000
10:121485480:A:C	Y704D	1.000
10:121485491:C:T	G700E	1.000
10:121485492:C:A	G700W	1.000
10:121485492:C:G	G700R	1.000
10:121485492:C:T	G700R	1.000
10:121485508:C:A	W694C	1.000
10:121485508:C:G	W694C	1.000
10:121485510:A:G	W694R	1.000
10:121485510:A:T	W694R	1.000
10:121485521:C:T	G690E	1.000
10:121485522:C:A	G690W	1.000
10:121485522:C:G	G690R	1.000
10:121485522:C:T	G690R	1.000
10:121485531:A:G	W687R	1.000
10:121485531:A:T	W687R	1.000
10:121487359:A:C	S684R	1.000
10:121487359:A:T	S684R	1.000
10:121487361:T:G	S684R	1.000
10:121487387:A:G	L675P	1.000
10:121487402:A:C	M670R	1.000
10:121487402:A:G	M670T	1.000
10:121487402:A:T	M670K	1.000
10:121487404:C:A	W669C	1.000

dbSNP variants (sampled 300 via entrez): RS1000049605 (10:121588352 G>A), RS1000067349 (10:121502313 G>A), RS1000125378 (10:121548993 C>G), RS1000134827 (10:121576423 C>G), RS1000151964 (10:121563651 C>T), RS1000178542 (10:121599097 G>A), RS1000185284 (10:121588141 C>T), RS1000216069 (10:121598843 A>C), RS1000227302 (10:121549801 T>C), RS1000263238 (10:121537300 A>C), RS1000285733 (10:121512629 A>G,T), RS1000287345 (10:121594082 T>C), RS1000302136 (10:121513984 C>G,T), RS1000316372 (10:121554034 C>T), RS1000326971 (10:121536740 A>G)

Disease associations

OMIM: gene MIM:176943 | disease phenotypes: MIM:613659, MIM:101200, MIM:101400, MIM:101600, MIM:123150, MIM:123500, MIM:123790, MIM:149730, MIM:609579, MIM:614592, MIM:207410, MIM:123100, MIM:224690, MIM:607842, MIM:609625, MIM:183600, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
Pfeiffer syndrome	Definitive	Autosomal dominant
Crouzon syndrome	Definitive	Autosomal dominant
LADD syndrome 1	Definitive	Autosomal dominant
Apert syndrome	Definitive	Autosomal dominant
Jackson-Weiss syndrome	Definitive	Autosomal dominant
bent bone dysplasia syndrome 1	Strong	Autosomal dominant
Saethre-Chotzen syndrome	Strong	Autosomal dominant
Beare-Stevenson cutis gyrata syndrome	Strong	Autosomal dominant
Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis	Strong	Autosomal dominant
familial scaphocephaly syndrome, McGillivray type	Strong	Autosomal dominant
LADD syndrome	Supportive	Autosomal dominant
Antley-Bixler syndrome	Supportive	Autosomal dominant
Pfeiffer syndrome type 1	Supportive	Autosomal dominant
Pfeiffer syndrome type 2	Supportive	Autosomal dominant
Pfeiffer syndrome type 3	Supportive	Autosomal dominant
acinar dysplasia caused by mutation in FGFR2	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (6)

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

Disease	Classification	Inheritance
Apert syndrome	Definitive	AD
bent bone dysplasia syndrome 1	Definitive	AD
Beare-Stevenson cutis gyrata syndrome	Definitive	AD
Crouzon syndrome	Definitive	AD
LADD syndrome	Limited	AD
Pfeiffer syndrome	Definitive	AD

Mondo (30): gastric cancer (MONDO:0001056), Apert syndrome (MONDO:0007041), Saethre-Chotzen syndrome (MONDO:0007042), Pfeiffer syndrome (MONDO:0007043), Jackson-Weiss syndrome (MONDO:0007400), Crouzon syndrome (MONDO:0007405), Beare-Stevenson cutis gyrata syndrome (MONDO:0007412), LADD syndrome (MONDO:0007872), familial scaphocephaly syndrome, McGillivray type (MONDO:0012307), bent bone dysplasia syndrome 1 (MONDO:0013815), Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (MONDO:0020667), LADD syndrome 1 (MONDO:0100302), glioblastoma (MONDO:0018177), disorder of sexual differentiation (MONDO:0002145), craniosynostosis (MONDO:0015469)

Orphanet (20): Jackson-Weiss syndrome (Orphanet:1540), Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome (Orphanet:1555), Familial scaphocephaly syndrome, McGillivray type (Orphanet:168624), Crouzon syndrome (Orphanet:207), Lacrimoauriculodentodigital syndrome (Orphanet:2363), FGFR2-related bent bone dysplasia (Orphanet:313855), Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis (Orphanet:596008), Pfeiffer syndrome (Orphanet:710), Saethre-Chotzen syndrome (Orphanet:794), Antley-Bixler syndrome (Orphanet:83), Apert syndrome (Orphanet:87), Glioblastoma (Orphanet:360), Difference of sex development (Orphanet:90771), Craniosynostosis (Orphanet:1531), Ear-patella-short stature syndrome (Orphanet:2554)

HPO phenotypes

369 total (30 of 369 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000059	Hypoplastic labia majora
HP:0000063	Fused labia minora
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000089	Renal hypoplasia
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000148	Vaginal atresia
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000193	Bifid uvula
HP:0000198	Absence of Stensen duct
HP:0000202	Orofacial cleft
HP:0000212	Gingival overgrowth
HP:0000217	Xerostomia
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000243	Trigonocephaly
HP:0000244	Brachyturricephaly
HP:0000248	Brachycephaly

GWAS associations

63 associations (top):

Study	Trait	p-value
GCST000035_2	Breast cancer	2.000000e-76
GCST000036_1	Breast cancer	1.000000e-10
GCST000365_6	Breast cancer	2.000000e-10
GCST000678_2	Breast cancer	4.000000e-31
GCST000811_4	Breast cancer	2.000000e-13
GCST000846_1	Breast cancer in BRCA2 mutation carriers	1.000000e-08
GCST000919_4	Serum prostate-specific antigen levels	5.000000e-15
GCST000952_6	Breast cancer	2.000000e-06
GCST000952_8	Breast cancer	1.000000e-30
GCST001667_2	Breast cancer	8.000000e-08
GCST001831_3	Breast cancer	2.000000e-06
GCST001937_38	Breast cancer	2.000000e-170
GCST002233_1	Adiponectin levels	3.000000e-14
GCST002234_1	Breast cancer	1.000000e-12
GCST002346_16	Breast cancer (early onset)	3.000000e-27
GCST002895_1	Breast cancer	4.000000e-06
GCST003195_2	Magnesium levels	3.000000e-07
GCST003588_12	Cancer (pleiotropy)	8.000000e-35
GCST003821_1	Estrogen receptor status in breast cancer	6.000000e-12
GCST003823_1	Estrogen receptor status in HER2 negative breast cancer	5.000000e-11
GCST003991_23	Childhood ear infection	8.000000e-07
GCST004093_13	Prostate-specific antigen levels	3.000000e-11
GCST004093_14	Prostate-specific antigen levels	4.000000e-18
GCST004093_15	Prostate-specific antigen levels	1.000000e-35
GCST004093_16	Prostate-specific antigen levels	4.000000e-43
GCST004093_8	Prostate-specific antigen levels	2.000000e-53
GCST004094_1	Prostate-specific antigen levels (conditioned on lead SNPs)	9.000000e-25
GCST004094_7	Prostate-specific antigen levels (conditioned on lead SNPs)	5.000000e-18
GCST004904_163	Body mass index	3.000000e-11
GCST004904_232	Body mass index	4.000000e-11

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0004845	magnesium measurement
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0005512	estrogen receptor status
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure
EFO:0009443	BRCAX breast cancer
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008008	lower urinary tract symptom
EFO:0004530	triglyceride measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0011013	vaginal microbiome measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D000168	Acrocephalosyndactylia	C05.116.099.370.894.232.015; C05.116.099.370.894.819.100; C05.660.207.240.100; C05.660.585.800.100; C05.660.906.364.100; C05.660.906.819.100; C16.131.621.207.240.100; C16.131.621.585.800.100; C16.131.621.906.364.100; C16.131.621.906.819.100
D003394	Craniofacial Dysostosis	C05.116.099.370.231; C05.660.207.231; C16.131.621.207.231
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D005909	Glioblastoma	C04.557.465.625.600.380.080.335; C04.557.470.670.380.080.335; C04.557.580.625.600.380.080.335
D006849	Hydrocephalus	C10.228.140.602
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D013274	Stomach Neoplasms	C04.588.274.476.767; C06.301.371.767; C06.405.249.767; C06.405.748.789
C564321	Aural Atresia, Congenital (supp.)
C567182	Chromosome 10q26 Deletion Syndrome (supp.)
C565129	Cutis Gyrata Syndrome of Beare And Stevenson (supp.)
C537559	Jackson-Weiss syndrome (supp.)
C538132	Lacrimoauriculodentodigital syndrome (supp.)
C566511	Scaphocephaly, Maxillary Retrusion, And Mental Retardation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2095217 (PROTEIN FAMILY), CHEMBL2111434 (SELECTIVITY GROUP), CHEMBL4142 (SINGLE PROTEIN), CHEMBL4802036 (PROTEIN COMPLEX), CHEMBL5291678 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066126 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

59 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 408,369 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL4297522	PEMIGATINIB	4	2,055
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3039504	NINTEDANIB ESYLATE	4	659
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3545376	ERDAFITINIB	4	2,794
CHEMBL3701238	FUTIBATINIB	4	813
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4
CHEMBL223360	LINIFANIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL124660	TANDUTINIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2

Clinical evidence (CIViC)

Drug × variant × indication: 13 predictive associations from 15 curated evidence items; also 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FGFR2 Mutation OR FGFR2::v Fusion OR FGFR2::? Fusion	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7261
FGFR2 Mutation	Infigratinib	Cholangiocarcinoma	Sensitivity/Response	CIViC B	EID5912 +1
FGFR2 Amplification	Dovitinib	Breast Cancer	Sensitivity/Response	CIViC B	EID1605
FGFR2 Amplification	Fexagratinib	Stomach Carcinoma	Sensitivity/Response	CIViC B	EID1990
FGFR2 Mutation	Dovitinib + Fulvestrant	Endometrial Cancer	Sensitivity/Response	CIViC B	EID6457
FGFR2 Mutation	Erdafitinib	Cholangiocarcinoma	Sensitivity/Response	CIViC C	EID10375 +1
FGFR2 Amplification	Futibatinib	Gastric Adenocarcinoma	Sensitivity/Response	CIViC C	EID11637
FGFR2 Amplification	Futibatinib	Triple-receptor Negative Breast Cancer	Sensitivity/Response	CIViC C	EID11648
FGFR2 P253R	Pazopanib	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC C	EID7833
FGFR2 Amplification	Erdafitinib	Stomach Cancer	Sensitivity/Response	CIViC D	EID7953
FGFR2 Amplification	Ponatinib	Stomach Cancer	Sensitivity/Response	CIViC D	EID8062
FGFR2 Mutation	Ponatinib	Endometrial Cancer	Sensitivity/Response	CIViC D	EID1236
FGFR2 N550K	PD173074	Endometrial Cancer	Sensitivity/Response	CIViC D	EID1322

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1219648	FGFR2		0.00	0
rs2981582	FGFR2		0.00	0
rs1057519045	FGFR2		0.00	0
rs1057519797	FGFR2		0.00	0

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 (24 total), top 24:

Ligand	Action	Affinity	Parameter
TYRA-200	Inhibition	10.0	pKd
bemarituzumab	Binding	9.24	pKd
compound 29 [PMID: 36356320]	Inhibition	9.0	pIC50
futibatinib	Inhibition	8.96	pIC50
segigratinib	Inhibition	8.89	pIC50
PRN1371	Inhibition	8.89	pIC50
infigratinib	Inhibition	8.85	pIC50
derazantinib	Inhibition	8.74	pIC50
erdafitinib	Inhibition	8.64	pIC50
LY2874455	Inhibition	8.59	pIC50
tasurgratinib	Inhibition	8.35	pIC50
fexagratinib	Inhibition	8.3	pIC50
compound 7 [Nguyen et al., 2023]	Inhibition	8.28	pIC50
fanregratinib	Inhibition	8.22	pIC50
zoligratinib	Inhibition	8.12	pIC50
alofanib	Inhibition	8.0	pIC50
nintedanib	Inhibition	7.43	pIC50
MK-2461	Inhibition	7.41	pIC50
vepugratinib	Inhibition	7.04	pIC50
lirafugratinib	Inhibition	7.0	pIC50
resigratinib	Inhibition	7.0	pIC50
pemigatinib	Inhibition	7.0	pIC50
dabogratinib	Inhibition	6.8	pIC50
BLU-9931	Inhibition	6.31	pIC50

Binding affinities (BindingDB)

660 measured of 1201 human assays (1213 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[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
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-5-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.355 nM	US-9757364: Naphthyridine derivative compounds
1-[(2S,4S)-4-[4-amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]pyrazolo[3,4-d]pyrimidin-1-yl]-2-ethynylpyrrolidin-1-yl]prop-2-en-1-one	IC50	0.4 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
1-[(3S)-3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]pyrrolidin-1-yl]prop-2-en-1-one	IC50	0.4 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1H-pyrazol-5-ylmethyl)-1,5-naphthyridin-2-amine	IC50	0.417 nM	US-9757364: Naphthyridine derivative compounds
8-chloro-N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.447 nM	US-9757364: Naphthyridine derivative compounds
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	0.501 nM	US-9757364: Naphthyridine derivative compounds
4-(2-fluoro-3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)butanenitrile	IC50	0.55 nM	US-9757364: Naphthyridine derivative compounds
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-pyrrolidin-1-ylbut-2-en-1-one	IC50	0.6 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(4-fluoropiperidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.67 nM	US-8829199: Aminopyrazole derivative
N-(3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-piperidin-4-yl-1,5-naphthyridin-2-amine	IC50	0.676 nM	US-9757364: Naphthyridine derivative compounds
2-(N-[8-chloro-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-3,5-dimethoxyanilino)ethanol	IC50	0.724 nM	US-9757364: Naphthyridine derivative compounds
3-(N-[8-chloro-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-3,5-dimethoxyanilino)propan-1-ol	IC50	0.794 nM	US-9757364: Naphthyridine derivative compounds
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[6-[(3-methyloxetan-3-yl)methoxy]-1H-indol-2-yl]methanone	IC50	0.81 nM	US-8829199: Aminopyrazole derivative
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1,3-oxazol-2-ylmethyl)-1,5-naphthyridin-2-amine	IC50	0.851 nM	US-9757364: Naphthyridine derivative compounds
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-pyridin-4-yl-1,5-naphthyridin-2-amine	IC50	0.851 nM	US-9757364: Naphthyridine derivative compounds
N’-(2,6-difluoro-3,5-dimethoxyphenyl)-N-methyl-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]ethane-1,2-diamine	IC50	0.912 nM	US-9757364: Naphthyridine derivative compounds
5-[(2,6-difluoro-3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)methyl]pyrrolidin-2-one	IC50	0.955 nM	US-9757364: Naphthyridine derivative compounds
N’-(2,6-difluoro-3,5-dimethoxyphenyl)-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-N-propan-2-ylethane-1,2-diamine	IC50	0.977 nM	US-9757364: Naphthyridine derivative compounds
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-[(3R)-3-hydroxypyrrolidin-1-yl]but-2-en-1-one	IC50	1 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
2-[(3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)methyl]-N,N-dimethylimidazole-1-sulfonamide	IC50	1 nM	US-9757364: Naphthyridine derivative compounds
5-[(2-fluoro-3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)methyl]pyrrolidin-2-one	IC50	1.07 nM	US-9757364: Naphthyridine derivative compounds
N’-(2-fluoro-3,5-dimethoxyphenyl)-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-N-propan-2-ylethane-1,2-diamine	IC50	1.1 nM	US-9757364: Naphthyridine derivative compounds
N-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(oxolan-2-ylmethyl)-1,5-naphthyridin-2-amine	IC50	1.15 nM	US-9757364: Naphthyridine derivative compounds
1-[3-[4-amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]pyrazolo[3,4-d]pyrimidin-1-yl]azetidin-1-yl]-4-hydroxybut-2-yn-1-one	IC50	1.2 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]-4a,7a-dihydropyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]prop-2-en-1-one	IC50	1.2 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-(diethylamino)but-2-en-1-one	IC50	1.2 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
1-[(2S,4S)-4-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]-2-(1,3,4-oxadiazol-2-yl)pyrrolidin-1-yl]prop-2-en-1-one	IC50	1.2 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
1-[(2R,4R)-4-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]-2-(1,3,4-oxadiazol-2-yl)pyrrolidin-1-yl]prop-2-en-1-one	IC50	1.2 nM	US-10124003: Therapeutic agent for FGFR inhibitor-resistant cancer
N’-(2-fluoro-3,5-dimethoxyphenyl)-N-methyl-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]ethane-1,2-diamine	IC50	1.2 nM	US-9757364: Naphthyridine derivative compounds
N’-(3,5-dimethoxyphenyl)-N’-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-N-propan-2-ylethane-1,2-diamine	IC50	1.26 nM	US-9757364: Naphthyridine derivative compounds
3-(3,5-dimethoxy-N-[7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-yl]anilino)propan-1-ol	IC50	1.26 nM	US-9757364: Naphthyridine derivative compounds
N’-(3,5-dimethoxyphenyl)-N’-[7-(1-ethylpyrazol-4-yl)-1,5-naphthyridin-2-yl]-N-propan-2-ylethane-1,2-diamine	IC50	1.29 nM	US-9757364: Naphthyridine derivative compounds
N-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)-1,5-naphthyridin-2-amine	IC50	1.29 nM	US-9757364: Naphthyridine derivative compounds
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(pyrimidin-2-ylmethyl)-1,5-naphthyridin-2-amine	IC50	1.35 nM	US-9757364: Naphthyridine derivative compounds
N-(2-fluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1H-1,2,4-triazol-5-ylmethyl)-1,5-naphthyridin-2-amine	IC50	1.35 nM	US-9757364: Naphthyridine derivative compounds
N-(3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-pyridin-3-yl-1,5-naphthyridin-2-amine	IC50	1.35 nM	US-9757364: Naphthyridine derivative compounds
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[6-(morpholin-4-ylmethyl)-1H-indol-2-yl]methanone	IC50	1.4 nM	US-8829199: Aminopyrazole derivative
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-(pyrrolidin-1-ylmethyl)-1H-indol-2-yl]methanone	IC50	1.4 nM	US-8829199: Aminopyrazole derivative
1-[(3S)-3-[4-amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]pyrazolo[3,4-d]pyrimidin-1-yl]pyrrolidin-1-yl]prop-2-yn-1-one	IC50	1.4 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
N-(3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(1H-1,2,4-triazol-5-ylmethyl)-1,5-naphthyridin-2-amine	IC50	1.45 nM	US-9757364: Naphthyridine derivative compounds
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-(propan-2-ylamino)but-2-en-1-one	IC50	1.5 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-[2-methoxyethyl(methyl)amino]but-2-en-1-one	IC50	1.5 nM	US-9108973: 3,5-disubstituted alkynylbenzene compound and salt thereof
(E)-1-[3-[4-amino-5-[2-(3,5-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidin-7-yl]azetidin-1-yl]-4-[ethyl(methyl)amino]but-2-en-1-one	IC50	1.5 nM	US-10124003: Therapeutic agent for FGFR inhibitor-resistant cancer
N-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-(2-propan-2-yloxyethyl)-1,5-naphthyridin-2-amine	IC50	1.55 nM	US-9757364: Naphthyridine derivative compounds
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(4-methylpiperazin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	1.6 nM	US-8829199: Aminopyrazole derivative
(S)-1-(3-(4-amino-3-(benzo[c]isothiazole-6-ethynylene)-7-propionyl-1H-pyrazolo[4,3-c]pyridin-1-yl)pyrrolidine-1-methyl)prop-2-en-1-one	IC50	1.6 nM	US-20250152564: PROPYLENE KETONE-CONTAINING BIOINHIBITOR, PREPARATION METHOD THEREFOR, AND USE THEREOF
Staurosporine	KD	1.7 nM
(S)-1-(3-(4-amino-3-((1-cyclopropyl-6-fluoro-1H-benzo[d]imidazol-5-yl)ethynyl)-7-propionyl-1H-pyrazolo[4,3-c]pyridin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one	IC50	1.7 nM	US-20250152564: PROPYLENE KETONE-CONTAINING BIOINHIBITOR, PREPARATION METHOD THEREFOR, AND USE THEREOF

ChEMBL bioactivities

2859 potent at pChembl≥5 of 2893 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.27	IC50	0.054	nM	ERDAFITINIB
10.09	IC50	0.081	nM	CHEMBL6102154
9.96	IC50	0.11	nM	CHEMBL5173892
9.96	IC50	0.11	nM	CHEMBL6133974
9.96	IC50	0.11	nM	ERDAFITINIB
9.92	IC50	0.121	nM	CHEMBL5589978
9.92	IC50	0.12	nM	LIRAFUGRATINIB
9.90	IC50	0.126	nM	CHEMBL6043032
9.82	IC50	0.15	nM	CHEMBL4870179
9.72	IC50	0.191	nM	CHEMBL6102182
9.72	IC50	0.19	nM	ERDAFITINIB
9.71	IC50	0.194	nM	CHEMBL6141687
9.70	IC50	0.2	nM	CHEMBL3798625
9.70	IC50	0.2	nM	CHEMBL3800526
9.70	IC50	0.2	nM	CHEMBL4862576
9.70	IC50	0.2	nM	CHEMBL5175256
9.70	IC50	0.2	nM	CHEMBL5189383
9.70	IC50	0.202	nM	ERDAFITINIB
9.65	IC50	0.223	nM	CHEMBL6102044
9.62	IC50	0.24	nM	PEMIGATINIB
9.59	IC50	0.26	nM	LY-2874455
9.57	IC50	0.27	nM	CHEMBL5171314
9.54	IC50	0.29	nM	CHEMBL5179660
9.52	IC50	0.3	nM	CHEMBL3797845
9.52	IC50	0.3	nM	CHEMBL3797507
9.52	IC50	0.3	nM	CHEMBL4091628
9.52	IC50	0.3	nM	CHEMBL4862823
9.52	IC50	0.3	nM	LY-2874455
9.44	IC50	0.36	nM	CHEMBL6074574
9.44	IC50	0.36	nM	FUTIBATINIB
9.40	IC50	0.4	nM	CHEMBL190161
9.40	IC50	0.4	nM	CHEMBL3798342
9.40	IC50	0.4	nM	CHEMBL3797594
9.40	IC50	0.4	nM	CHEMBL3701256
9.40	IC50	0.4	nM	CHEMBL3701258
9.40	IC50	0.4	nM	FEXAGRATINIB
9.40	IC50	0.4	nM	PEMIGATINIB
9.40	IC50	0.4	nM	CHEMBL5857112
9.39	IC50	0.41	nM	LY-2874455
9.38	IC50	0.42	nM	ERDAFITINIB
9.37	IC50	0.43	nM	CHEMBL5205436
9.36	IC50	0.437	nM	CHEMBL5189958
9.36	IC50	0.441	nM	CHEMBL6096574
9.35	IC50	0.449	nM	CHEMBL5589978
9.35	IC50	0.448	nM	CHEMBL6078421
9.34	IC50	0.46	nM	INFIGRATINIB
9.33	IC50	0.47	nM	ASP-5878
9.30	IC50	0.5	nM	CHEMBL191023
9.30	IC50	0.5	nM	CHEMBL191070
9.30	IC50	0.5	nM	CHEMBL3797416

PubChem BioAssay actives

853 with measured affinity, of 2351 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
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-propan-2-ylpiperazin-1-yl)quinazolin-4-amine	1298508: Inhibition of recombinant FGFR2 in human SNU16 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0001	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]quinazolin-4-amine	1298508: Inhibition of recombinant FGFR2 in human SNU16 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0001	uM
7-(4-cyclobutylpiperazin-1-yl)-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]quinazolin-4-amine	1298508: Inhibition of recombinant FGFR2 in human SNU16 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0001	uM
(2R,6S)-4-[2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-3H-benzimidazol-5-yl]-2,6-dimethylmorpholine	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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	0.0001	uM
N-[2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethyl]-6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]hexanamide	2116636: Inhibition of FGFR2 V564F mutant (unknown origin)	ic50	0.0001	uM
11-(2,6-difluoro-3,5-dimethoxyphenyl)-13-methyl-5,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1,3,6,8-tetraen-12-one	1751594: Inhibition of human FGFR2 using biotinylated-EQEDEPEGDYFEWLE peptide as substrate incubated for 1 hr in presence of ATP by FRET assay	ic50	0.0001	uM
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	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (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	1849334: Inhibition of N-terminal GST tagged recombinant human FGFR2 (400 to 821 residues) expressed in an Sf9 infected baculovirus expression system 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-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]-3-(1-methylpyrazol-4-yl)pyrido[1,2-a]pyrimidin-4-one	1778444: Inhibition of human N-terminal GST fusion tagged FGFR2 cytoplasmic domain (399 to 821 end residues) expressed in baculovirus infected Sf21 insect cells	ic50	0.0002	uM
5-[5-[[(3S)-oxolan-3-yl]amino]-6-(1-propan-2-ylpyrazol-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(trideuteriomethyl)pyridine-3-carboxamide	1849334: Inhibition of N-terminal GST tagged recombinant human FGFR2 (400 to 821 residues) expressed in an Sf9 infected baculovirus expression system 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
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(5-morpholin-4-yl-3-pyridinyl)ethynyl]benzamide	1435445: Inhibition of recombinant FGFR2 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0003	uM
N-[5-[2-(2,6-dichloro-3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-ethylpiperazin-1-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-[4-(dimethylamino)piperidin-1-yl]quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0003	uM
4-[2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-fluoro-1H-benzimidazol-5-yl]morpholine	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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	0.0003	uM
(2R,6S)-4-[2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-fluoro-1H-benzimidazol-5-yl]-2,6-dimethylmorpholine	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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	0.0003	uM
2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloro-4-pyridinyl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol	1934915: Inhibition of wild type FGFR2 (unknown origin)	ic50	0.0003	uM
11-(2-chloro-6-fluoro-3,5-dimethoxyphenyl)-13-methyl-5,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1,3,6,8-tetraen-12-one	1751594: Inhibition of human FGFR2 using biotinylated-EQEDEPEGDYFEWLE peptide as substrate incubated for 1 hr in presence of ATP by FRET assay	ic50	0.0003	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-[3-(dimethylamino)pyrrolidin-1-yl]quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0004	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-morpholin-4-ylquinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0004	uM
2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-fluoro-5-(4-methylpiperazin-1-yl)-1H-benzimidazole	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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
2-[5-[2-(2,6-dichloro-3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide	1516663: Inhibition of human FGFR2 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA	ic50	0.0004	uM
1-tert-butyl-3-[3-(3,5-dimethoxyphenyl)-7-[4-(4-methylpiperazin-1-yl)butylamino]-1,6-naphthyridin-2-yl]urea	248789: Inhibition of FGF-dependent human umbilical vein endothelial cell proliferation	ic50	0.0004	uM
Pemigatinib	1849334: Inhibition of N-terminal GST tagged recombinant human FGFR2 (400 to 821 residues) expressed in an Sf9 infected baculovirus expression system 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	0.0004	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2-ethyl-7-(4-ethylpiperazin-1-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0005	uM
2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-(1-piperidin-4-ylpyrazol-4-yl)-1,3,5-triazin-2-amine	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-(1-methylpyrazol-4-yl)-1,3,5-triazin-2-amine	1880028: Inhibition of FGFR2 N549H mutant (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-[1-(1-propan-2-ylpiperidin-4-yl)pyrazol-4-yl]-1,3,5-triazin-2-amine	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-[4-(4-ethylpiperazin-1-yl)phenyl]-1,3,5-triazin-2-amine	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-[3-(4-ethylpiperazin-1-yl)phenyl]-1,3,5-triazin-2-amine	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]phenyl]-1,3,5-triazin-2-amine	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
Infigratinib	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
1-tert-butyl-3-[7-[4-(diethylamino)butylamino]-3-(3,5-dimethoxyphenyl)-1,6-naphthyridin-2-yl]urea	248925: Inhibition of FGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0005	uM
1-tert-butyl-3-[3-(3,5-dimethoxyphenyl)-7-(5-morpholin-4-ylpentylamino)-1,6-naphthyridin-2-yl]urea	248789: Inhibition of FGF-dependent human umbilical vein endothelial cell proliferation	ic50	0.0005	uM
Erdafitinib	1880022: Inhibition of wild-type FGFR2 (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
2-[4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]pyrimidin-2-yl]amino]pyrazol-1-yl]ethanol	1911607: Inhibition of recombinant FGFR2 (unknown origin) by mobility assay	ic50	0.0005	uM
6-(2-hydroxyethoxy)-5-[[2-[[4-[1-(2-hydroxyethyl)piperidin-4-yl]benzoyl]amino]-4-pyridinyl]oxy]-N-methylindole-1-carboxamide	1404632: Inhibition of human N-terminal GST-tagged FGFR2 (399 to 821 residues) cytoplasmic domain expressed in baculovirus expression system after 60 mins by off-chip mobility shift assay	ic50	0.0005	uM
2-chloro-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-ethylpiperazin-1-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0006	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-ethylpiperazin-1-yl)-2-methylquinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0006	uM
2-[5-[2-(2,6-dichloro-3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-[(4-methylpiperazin-1-yl)methyl]-1H-benzimidazole	1845247: Inhibition of recombinant N-terminal GST-tagged human FGFR2 (399 to 821 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	0.0006	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	1626475: Inhibition of human FGFR2 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0007	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-methylpiperazin-1-yl)quinazolin-4-amine	1298508: Inhibition of recombinant FGFR2 in human SNU16 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0007	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0007	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-ethylpiperazin-1-yl)-2-propylquinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0007	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-[4-(2-methoxyethyl)piperazin-1-yl]quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0007	uM
(E)-1-[4-[5-[4-amino-3-(3,5-dimethoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]pentyl]piperazin-1-yl]-4,4,4-trifluorobut-2-en-1-one	1810703: Inhibition of human FGFR2 (458 to 768 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay	ic50	0.0007	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(4-ethylpiperazin-1-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0008	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-7-(1-methylpiperidin-4-yl)quinazolin-4-amine	1298506: Inhibition of recombinant FGFR2 (unknown origin) using (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0008	uM
7-anilino-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-4-yl]-4H-pyrimido[4,5-d]pyrimidin-2-one	1460987: Inhibition of human recombinant cytoplasmic His-tagged FGFR2 (403 to 822 residues) expressed in baculovirus using Tyr-4 peptide after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, affects reaction, decreases expression	6
Particulate Matter	decreases expression, increases abundance, decreases methylation, increases expression	5
futibatinib	increases response to substance, affects binding, decreases activity	4
Ethinyl Estradiol	affects expression, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Genistein	increases expression, increases reaction, decreases expression	3
ponatinib	decreases activity	2
Acetaminophen	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, decreases methylation, increases expression	2
Vehicle Emissions	decreases expression, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Cisplatin	affects response to substance, decreases expression	2
Heparin	affects binding, increases activity, increases reaction	2
Nickel	decreases expression	2
Silicon Dioxide	decreases expression	2
Tamoxifen	decreases expression, decreases reaction, decreases response to substance, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
perfluorodecanesulfonic acid	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
cinnamaldehyde	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1

ChEMBL screening assays

966 unique, capped per target: 940 binding, 22 functional, 4 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
CHEMBL4262864	ADMET	Inhibition of phosphorylated FGFR2 (406 to 821 residues) (unknown origin) using 5-Fluo-Ahx-EEPLYWSFPAKKKCONH2 as substrate after 60 mins by microfluidic mobility shift assay	Approaches to selective fibroblast growth factor receptor 4 inhibition through targeting the ATP-pocket middle-hinge region. — Medchemcomm

Cellosaurus cell lines

18 cell lines: 17 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_6020	SK-MEL-10	Cancer cell line	Sex unspecified
CVCL_A1UZ	ICC10-6	Cancer cell line	Male
CVCL_A1VA	ICC10-8	Cancer cell line	Male
CVCL_A1VB	ICC10	Cancer cell line	Male
CVCL_A1VD	ICC13-7	Cancer cell line	Female
CVCL_B8G1	Abcam HCT 116 FGFR2 KO	Cancer cell line	Male
CVCL_B8VU	Abcam MCF-7 FGFR2 KO	Cancer cell line	Female
CVCL_B9I8	Abcam A-549 FGFR2 KO	Cancer cell line	Male
CVCL_D8LC	Ubigene HCT 116 FGFR2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients