FGFR3

Summary

FGFR3 (fibroblast growth factor receptor 3, HGNC:3690) is a protein-coding gene on chromosome 4p16.3, encoding Fibroblast growth factor receptor 3 (P22607). 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 and apoptosis. In precision oncology, FGFR3 G370C confers sensitivity to Erdafitinib in Transitional Cell Carcinoma (CIViC Level A); 41 further curated variant–drug associations are listed below.

This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist 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 acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia.

Source: NCBI Gene 2261 — RefSeq curated summary.

At a glance

• Gene–disease (curated): achondroplasia (Definitive, ClinGen) — +13 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,229 total — 37 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 338
• Druggable target: yes — 64 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 42 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3690
Approved symbol	FGFR3
Name	fibroblast growth factor receptor 3
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	CEK2, JTK4, CD333
Ensembl gene	ENSG00000068078
Ensembl biotype	protein_coding
OMIM	134934
Entrez	2261

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000260795, ENST00000340107, ENST00000352904, ENST00000412135, ENST00000440486, ENST00000469068, ENST00000474521, ENST00000481110, ENST00000507588, ENST00000643463, ENST00000901225, ENST00000901226, ENST00000901227, ENST00000901228, ENST00000911470, ENST00000911471, ENST00000911472, ENST00000911473, ENST00000911474, ENST00000955401, ENST00000955402, ENST00000955403, ENST00000955404

RefSeq mRNA: 5 — MANE Select: NM_000142 NM_000142, NM_001163213, NM_001354809, NM_001354810, NM_022965

CCDS: CCDS3353, CCDS3354, CCDS54706, CCDS87200

Canonical transcript exons

ENST00000440486 — 18 exons

Exon	Start	End
ENSE00000778155	1799747	1799812
ENSE00000778157	1801620	1801743
ENSE00000778159	1803692	1803836
ENSE00000778160	1804330	1804520
ENSE00000843002	1804824	1804969
ENSE00000933877	1801367	1801536
ENSE00001164902	1799254	1799523
ENSE00001596390	1793833	1794043
ENSE00001604810	1806051	1806173
ENSE00001676483	1806257	1806327
ENSE00001744397	1793293	1793465
ENSE00001768214	1805750	1805940
ENSE00002246626	1807116	1808867
ENSE00003494331	1801835	1802025
ENSE00003518612	1806829	1806934
ENSE00003521592	1805355	1805476
ENSE00003575180	1806546	1806683
ENSE00003655496	1805559	1805669

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4107 / max 104.6870, expressed in 754 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46571	6.2525	747
46572	0.1582	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.52	gold quality
skin of hip	UBERON:0001554	99.40	gold quality
upper arm skin	UBERON:0004263	99.28	gold quality
gingival epithelium	UBERON:0001949	99.13	gold quality
tibia	UBERON:0000979	99.08	gold quality
gingiva	UBERON:0001828	99.00	gold quality
lateral globus pallidus	UBERON:0002476	98.95	gold quality
cervix squamous epithelium	UBERON:0006922	98.90	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.75	gold quality
medial globus pallidus	UBERON:0002477	98.73	gold quality
globus pallidus	UBERON:0001875	98.69	gold quality
cranial nerve II	UBERON:0000941	98.62	gold quality
skin of abdomen	UBERON:0001416	98.58	gold quality
penis	UBERON:0000989	98.51	gold quality
inferior olivary complex	UBERON:0002127	98.46	gold quality
pharyngeal mucosa	UBERON:0000355	98.34	gold quality
pancreatic ductal cell	CL:0002079	98.32	gold quality
nipple	UBERON:0002030	98.31	gold quality
zone of skin	UBERON:0000014	98.30	gold quality
squamous epithelium	UBERON:0006914	98.23	gold quality
skin of leg	UBERON:0001511	98.22	gold quality
ventricular zone	UBERON:0003053	98.19	gold quality
lower esophagus mucosa	UBERON:0035834	98.18	gold quality
ventral tegmental area	UBERON:0002691	98.08	gold quality
renal medulla	UBERON:0000362	97.95	gold quality
medulla oblongata	UBERON:0001896	97.84	gold quality
superior vestibular nucleus	UBERON:0007227	97.78	gold quality
nucleus accumbens	UBERON:0001882	97.75	gold quality
esophagus squamous epithelium	UBERON:0006920	97.67	gold quality
periodontal ligament	UBERON:0008266	97.66	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	23.88
E-CURD-112	yes	13.20
E-GEOD-84465	yes	12.17
E-ANND-3	yes	11.42
E-CURD-114	no	171.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL2, DNMT3B, EGR1, ESR1, NR2F2, PROX1, RUNX2, SHOX, SP1, SP3, SP4, SPI1, SRF, STAT1, TP63, TP73, ZBTB16, ZNF699

miRNA regulators (miRDB)

84 targeting FGFR3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• G380R mutation of this gene is common mutation associated with achondroplasia (PMID:11556601)
• We identified a novel ETV6 partner gene, fibroblast growth factor receptor 3 (FGFR3), in a patient with peripheral T-cell lymphoma (PTCL) with a t(4;12)(p16;p13) translocation. (PMID:11731410)
• Two patients with clinical and radiological findings of achondroplasia, who had the most common FGFR3 missense mutations. (PMID:11754059)
• distribution in normal endocrine cells and related tumors of the gastroenteropancreatic system; immunoreactive in duodenal G cells (PMID:11759058)
• interacts with adapter protein SH2-B, and has a role in STAT5 activation (PMID:11827956)
• Identification and characterization of an alternatively spliced isoform (PMID:11906172)
• the G370C and S371C mutant receptors spontaneously dimerize in the correct spatial orientation required for effective signal transduction, whereas the 372-5 mutants, like the WT receptor, may achieve this orientation only on ligand binding (PMID:12009017)
• Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. (PMID:12048679)
• phosphorylation is essential for FGFR3 ubiquitylation, but is not sufficient to induce downregulation of its internalization resistant mutants (PMID:12297284)
• there is an FGFR3 mutation with a demonstrated deregulatory mechanism and alternative splicing in the absence of t(4;14) in multiple myeloma patients (PMID:12368157)
• Parathyroid hormone receptor type 1/Indian hedgehog expression is preserved in the growth plate of human fetuses affected with activating mutations in this protein (PMID:12368206)
• 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)
• strong correlation beween mutations of FGFR3 and disturbances of skeletal growth-REVIEW (PMID:12424440)
• data indicate that t(4;14)(p16;q32) and loss of fibroblast growth factor receptor 3 occurred at a very early stage of multiple myeloma and suggest that activation of multiple myeloma SET domain protein may be transforming event of this translocation (PMID:12433679)
• mutations in bladder cancer previously identified in non-lethal skeletal disorders (PMID:12461689)
• the importance of the immature FGFR3 proteins as mediators of an abnormal signaling in thanatophoric dysplasia type II (PMID:12624096)
• Cherubism was mapped to region 4p16.3. Because of the associated craniosynostosis, we excluded the FGFR3 gene as a candidate gene for cherubism. (PMID:12664252)
• The FGFR3-associated coronal synostosis syndrome (Muenke craniosynostosis) is caused by a point mutation (C749G) on the FGFR3 gene resulting in a Pro250Arg substitution. (PMID:12764678)
• A missense mutation in FGFR3 resulted in skeltal dysplasia distinct from thanatophoric dysplasia. (PMID:12833394)
• results give further support to the fact that the G380R mutation of FGFR-3 is the most common mutation causing achondroplasia in different populations (PMID:12921294)
• introduction of these mutated FGFR3s into ATDC5 cells downregulated PTHrP expression and induced apoptosis with reduction of Bcl-2 expression (PMID:12929929)
• FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype (PMID:14520460)
• involvement of FGFR-3 in malignant hematopoiesis and FGFR-3 tyrosine kinase in CD34+ leukemic cells (PMID:14562121)
• IGF-1 prevents the apoptosis induced by FGFR3 mutation through the PI3K pathway and MAPK pathway (PMID:14606518)
• FGFR3 mutations were associated with low-stage, low-grade urothelial carcinomas of the blader. (PMID:14678961)
• Inhibition of FGFR3 in myeloma cell lines was associated with morphologic, phenotypic, and functional changes typical of plasma cell differentiation, including increase in light-chain secretion and expression of CD31, followed by apoptosis (PMID:14715624)
• defective differentiation of chondrocytes is the main cause of longitudinal bone growth retardation in FGFR3-related human chondrodysplasias (PMID:14751560)
• Mutations in growth factor receptor 3 is associated with the pathogenesis of urothelial cell carcinoma (PMID:15026322)
• fibroblast growth factor receptor 3 activation is regulated by cytoplasmic tyrosine kinase Pyk2 (PMID:15105428)
• fibroblast growth factor receptor 3 has a role in trafficking and signaling (PMID:15292251)
• Acanthosis nigricans with achondroplasia due to Gly380Arg mutation in FGFR3. (PMID:15517832)
• 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)
• Over expression of FGFR3 is associated with urinary tract carcinoma progression (PMID:15701828)
• Activating mutations of FGFR3 are associated with benign skin tumors. (PMID:15772091)
• FGFR3 is an important cell survival and antiapoptotic factor for multiple myeloma cells (PMID:15788896)
• tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening (PMID:15869706)
• Mutation in the FGFR3 is associated with progression of oral squamous cell car (PMID:15880580)
• presence of a Pro250Arg mutation predisposed to an increased transcranial reoperation rate…on the basis of raised intracranial pressure…in apparently “isolated” coronal synostosis (PMID:15915095)
• results indicate that FGFR 3 plays a crucial role in the accelerated proliferation of MM carrying t(4;14)(p16.3;q32) (PMID:15940250)
• FGFR3 and Tp53 mutations do not appear to be associated with progression of T1G3 transitional bladder carcinomas (PMID:16061860)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgfr3	ENSDARG00000004782
mus_musculus	Fgfr3	ENSMUSG00000054252
rattus_norvegicus	Fgfr3	ENSRNOG00000016818

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), 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 3 — P22607 (reviewed: P22607)

All UniProt accessions (6): P22607, A0A7I2RW32, F8W9L4, I6LM06, Q96T34, X5D2G8

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 and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. 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. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.

Subunit / interactions. Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6; FGF8, FGF9, FGF10, FGF17, FGF18, FGF19, FGF20 and FGF23 (in vitro). Interacts with KLB. 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 PIK3R1, PLCG1, SOCS1 and SOCS3. Isoform 3 forms disulfide-linked dimers.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Endoplasmic reticulum Cell membrane Secreted Cell membrane.

Tissue specificity. Expressed in brain, kidney and testis. Very low or no expression in spleen, heart, and muscle. In 20- to 22-week old fetuses it is expressed at high level in kidney, lung, small intestine and brain, and to a lower degree in spleen, liver, and muscle. Isoform 2 is detected in epithelial cells. Isoform 1 is not detected in epithelial cells. Isoform 1 and isoform 2 are detected in fibroblastic 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. Phosphorylation at Tyr-724 is essential for stimulation of cell proliferation and activation of PIK3R1, STAT1 and MAP kinase signaling. Phosphorylation at Tyr-760 is required for interaction with PIK3R1 and PLCG1. Ubiquitinated. Is rapidly ubiquitinated after ligand binding and autophosphorylation, leading to receptor internalization and degradation. Subject to both proteasomal and lysosomal degradation. 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. Achondroplasia (ACH) [MIM:100800] A frequent form of short-limb dwarfism. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. ACH is an autosomal dominant disease. The disease is caused by variants affecting the gene represented in this entry. Crouzon syndrome with acanthosis nigricans (CAN) [MIM:612247] Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures), and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies), CAN, is considered to be an independent disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas, and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosomal dominant mode of inheritance. The disease is caused by variants affecting the gene represented in this entry. Thanatophoric dysplasia 1 (TD1) [MIM:187600] A neonatal lethal skeletal dysplasia. Affected individuals manifest severe shortening of the limbs with macrocephaly, narrow thorax, short ribs, and curved femurs. The disease is caused by variants affecting the gene represented in this entry. Thanatophoric dysplasia 2 (TD2) [MIM:187601] A neonatal lethal skeletal dysplasia causing severe shortening of the limbs, narrow thorax and short ribs. Patients with thanatophoric dysplasia type 2 have straight femurs and cloverleaf skull. The disease is caused by variants affecting the gene represented in this entry. Hypochondroplasia (HCH) [MIM:146000] Autosomal dominant disease and is characterized by disproportionate short stature. It resembles achondroplasia, but with a less severe phenotype. The disease is caused by variants affecting the gene represented in this entry. Bladder cancer (BLC) [MIM:109800] A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Disease susceptibility is associated with variants affecting the gene represented in this entry. Somatic mutations can constitutively activate FGFR3. Cervical cancer (CERCA) [MIM:603956] A malignant neoplasm of the cervix, typically originating from a dysplastic or premalignant lesion previously present at the active squamocolumnar junction. The transformation from mild dysplastic to invasive carcinoma generally occurs slowly within several years, although the rate of this process varies widely. Carcinoma in situ is particularly known to precede invasive cervical cancer in most cases. Cervical cancer is strongly associated with infection by oncogenic types of human papillomavirus. The gene represented in this entry is involved in disease pathogenesis. Camptodactyly, tall stature, and hearing loss syndrome (CATSHLS) [MIM:610474] An autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet, tall stature, scoliosis and/or a pectus excavatum, and hearing loss. Affected individuals have developmental delay and/or intellectual disability, and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam, each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy, progressed variably in early childhood, and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain, middle ear, and inner ear are structurally normal. The disease is caused by variants affecting the gene represented in this entry. Multiple myeloma (MM) [MIM:254500] A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving FGFR3 is found in multiple myeloma. Translocation t(4;14)(p16.3;q32.3) with the IgH locus. Lacrimo-auriculo-dento-digital syndrome 2 (LADD2) [MIM:620192] 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 may be caused by variants affecting the gene represented in this entry. Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900] Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. The disease is caused by variants affecting the gene represented in this entry. Muenke syndrome (MNKS) [MIM:602849] A condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis), which affects the shape of the head and face. It may be uni- or bilateral. When bilateral, it is characterized by a skull with a small antero-posterior diameter (brachycephaly), often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet, sensorineural hearing loss, intellectual disability and respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry. Keratosis, seborrheic (KERSEB) [MIM:182000] A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. The disease is caused by variants affecting the gene represented in this entry. Testicular germ cell tumor (TGCT) [MIM:273300] A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The gene represented in this entry may be involved in disease pathogenesis. Achondroplasia, severe, with developmental delay and acanthosis nigricans (SADDAN) [MIM:616482] A severe form of achondroplasia associated with developmental delay and acanthosis nigricans. Patients manifest short-limb dwarfism, with a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Acanthosis nigricans is a skin condition characterized by brown-pigmented, velvety verrucosities in body folds and creases. 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 SU5402.

Domain organisation. The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P22607-1	1, IIIc	yes
P22607-2	2, IIIb
P22607-3	3, FGFR3deltaTM
P22607-4	4

RefSeq proteins (5): NP_000133, NP_001156685, NP_001341738, NP_001341739, NP_075254 (=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, PF21165

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 (119 total): strand 28, sequence variant 28, helix 17, mutagenesis site 7, modified residue 6, glycosylation site 6, domain 4, turn 3, disulfide bond 3, splice variant 3, region of interest 2, compositionally biased region 2, binding site 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
9KFU	X-RAY DIFFRACTION	1.4
9D1X	X-RAY DIFFRACTION	1.6
8UDU	X-RAY DIFFRACTION	1.74
9VMB	X-RAY DIFFRACTION	1.97
6PNX	X-RAY DIFFRACTION	2.2
4K33	X-RAY DIFFRACTION	2.34
8UDV	X-RAY DIFFRACTION	2.35
6LVM	X-RAY DIFFRACTION	2.53
9CD7	X-RAY DIFFRACTION	2.53
7DHL	X-RAY DIFFRACTION	2.57
9VM9	X-RAY DIFFRACTION	2.65
8UDT	X-RAY DIFFRACTION	2.83
1RY7	X-RAY DIFFRACTION	3.2
7YSU	ELECTRON MICROSCOPY	3.2
2LZL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22607-F1	75.25	0.38

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): 617 (proton acceptor)

Ligand- & substrate-binding residues (2): 478–486; 508

Post-translational modifications (6): 444, 445, 647, 648, 724, 760

Disulfide bonds (3): 61–109, 176–228, 275–339

Glycosylation sites (6): 98, 225, 262, 294, 315, 328

Mutagenesis-validated functional residues (7):

Position	Phenotype
508	loss of kinase activity. abolishes ubiquitination.
577	minor effect on kinase activity.
650	constitutively activated kinase.
724	strongly reduced kinase activity. strongly reduced mitogen activity.
760	minor effect on kinase activity.
770	minor effect on kinase activity. increased mitogen activity.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1839130	Signaling by activated point mutants of FGFR3
R-HSA-2033515	t(4;14) translocations of FGFR3
R-HSA-5655332	Signaling by FGFR3 in disease
R-HSA-8853334	Signaling by FGFR3 fusions in cancer
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-190371	FGFR3b ligand binding and activation
R-HSA-190372	FGFR3c ligand binding and activation
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654227	Phospholipase C-mediated cascade; FGFR3
R-HSA-5654704	SHC-mediated cascade:FGFR3
R-HSA-5654706	FRS-mediated FGFR3 signaling
R-HSA-5654710	PI-3K cascade:FGFR3
R-HSA-5654732	Negative regulation of FGFR3 signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 960 (showing top): MODULE_52, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, JAEGER_METASTASIS_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, KEGG_MAPK_SIGNALING_PATHWAY, REACTOME_SIGNALING_BY_FGFR, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, TGACCTY_ERR1_Q2

GO Biological Process (28): MAPK cascade (GO:0000165), skeletal system development (GO:0001501), endochondral ossification (GO:0001958), chondrocyte differentiation (GO:0002062), endochondral bone growth (GO:0003416), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), positive regulation of phospholipase activity (GO:0010518), bone mineralization (GO:0030282), chondrocyte proliferation (GO:0035988), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), positive regulation of MAPK cascade (GO:0043410), negative regulation of developmental growth (GO:0048640), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), bone morphogenesis (GO:0060349), positive regulation of ERK1 and ERK2 cascade (GO:0070374), bone maturation (GO:0070977), fibroblast growth factor receptor apoptotic signaling pathway (GO:1902178), ossification (GO:0001503), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), cell population proliferation (GO:0008283), positive regulation of cell communication (GO:0010647), positive regulation of signaling (GO:0023056), skeletal system morphogenesis (GO:0048705), cartilage development (GO:0051216)

GO Molecular Function (11): protein tyrosine kinase activity (GO:0004713), fibroblast growth factor receptor activity (GO:0005007), ATP binding (GO:0005524), fibroblast growth factor binding (GO:0017134), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane receptor protein tyrosine kinase activity (GO:0004714), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), transport vesicle (GO:0030133), signaling receptor complex (GO:0043235), focal adhesion (GO:0005925), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Downstream signaling of activated FGFR3	4
FGFR3 mutant receptor activation	3
FGFR3 ligand binding and activation	2
Signaling by FGFR in disease	1
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Signaling by FGFR3	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	3
cytoplasm	3
endomembrane system	3
cell population proliferation	2
positive regulation of intracellular signal transduction	2
bone development	2
fibroblast growth factor receptor signaling pathway	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
system development	1
replacement ossification	1
endochondral bone morphogenesis	1
cell differentiation	1
cartilage development	1
bone growth	1
cell surface receptor signaling pathway via STAT	1
cell communication	1
signaling	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
ossification	1
biomineral tissue development	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
positive regulation of peptidyl-tyrosine phosphorylation	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of growth	1
developmental growth	1
regulation of developmental growth	1
negative regulation of developmental process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
animal organ morphogenesis	1
skeletal system morphogenesis	1

Protein interactions and networks

STRING

3043 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGFR3	FGF2	P09038	997
FGFR3	FGF13	Q92913	997
FGFR3	FGF8	P55075	995
FGFR3	FGF1	P05230	995
FGFR3	FGF9	P31371	995
FGFR3	FGF18	O76093	994
FGFR3	FGF17	O60258	956
FGFR3	TACC3	Q9Y6A5	938
FGFR3	KL	Q9UEF7	938
FGFR3	FGF23	Q9GZV9	937
FGFR3	FGF10	O15520	932
FGFR3	FGF3	P11487	932
FGFR3	PIK3CA	P42336	902
FGFR3	IGHV4-38-2	P0DP08	896
FGFR3	FGF7	P21781	882

IntAct

1100 interactions, top by confidence:

A	B	Type	Score
FGFR3	FGFR3	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
FGFR3	FGFR3	psi-mi:“MI:0407”(direct interaction)	0.730
FGFR3	STIM1	psi-mi:“MI:0915”(physical association)	0.660
CDS2	FGFR3	psi-mi:“MI:0915”(physical association)	0.660
HSD17B12	FGFR3	psi-mi:“MI:0915”(physical association)	0.660
AIF1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
BCAT1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
CAPN3	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
CDK2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
TEN1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
CDKN1A	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
COL2A1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
COMT	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
COX4I1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
CREM	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
DLX3	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
DPYS	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
HBEGF	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
DVL2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
ENSA	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
EZH2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
FOSL2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GATA1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GATA2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (367): FGFR3 (Affinity Capture-MS), FGFR3 (Affinity Capture-MS), FGFR3 (Two-hybrid), GRB2 (Co-fractionation), ILKAP (Co-fractionation), FGFR3 (Biochemical Activity), FGFR3 (Reconstituted Complex), FGFR3 (Reconstituted Complex), FGFR3 (Negative Genetic), VHL (Negative Genetic), FNTA (Negative Genetic), FGFR3 (Negative Genetic), FGFR3 (Affinity Capture-MS), FGFR3 (Affinity Capture-MS), FGFR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8P0N4K0, A2AB59, B4F7F3, D3YZU1, D3ZD05, O35681, O75427, O95382, P22455, P22607, P40748, P55144, P70218, Q06418, Q14160, Q1LZH7, Q2PS20, Q32P44, Q495M9, Q4ACU6, Q4H4B6, Q505F5, Q5F488, Q61851, Q63ZY3, Q6P9K8, Q6TLK4, Q6ZUM4, Q7KRY7, Q80T11, Q80U72, Q8BH60, Q8BX02, Q8N1G4, Q8TE68, Q8VC03, Q8VHK1, Q8VHK2, Q8WXD9, Q8WXE0

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

27 interactions.

A	Effect	B	Mechanism
FGFR3	“up-regulates activity”	FGFR3	phosphorylation
FGFR3	“down-regulates activity”	FGFR3	phosphorylation
FGF2	up-regulates	FGFR3	binding
BGJ-398	down-regulates	FGFR3	“chemical inhibition”
“Brivanib alaninate”	down-regulates	FGFR3	“chemical inhibition”
FGFR3	unknown	PTEN	phosphorylation
FGF1	up-regulates	FGFR3	binding
PD173074	down-regulates	FGFR3	“chemical inhibition”
FGFR3	“up-regulates activity”	STAT1	phosphorylation
FGFR3	“up-regulates activity”	STAT3	phosphorylation
ponatinib	“down-regulates activity”	FGFR3	“chemical inhibition”
FGFR3	“down-regulates quantity by destabilization”	TET2	phosphorylation
FGFR3	“up-regulates activity”	MAP3K7	phosphorylation
hsa-mir-152-3p	“down-regulates quantity by destabilization”	FGFR3	“post transcriptional regulation”
nintedanib	“down-regulates activity”	FGFR3	“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”	FGFR3	“chemical inhibition”
4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone	“down-regulates activity”	FGFR3	“chemical inhibition”
“pazopanib hydrochloride”	“down-regulates activity”	FGFR3	“chemical inhibition”
FGFR3	“up-regulates activity”	GLO1	phosphorylation
FGFR3	“down-regulates activity”	CILK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 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.

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	5	19.8×	2e-03
positive regulation of miRNA transcription	9	14.8×	7e-06
cell fate commitment	6	10.0×	9e-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 7 cancer types — BLADDER, BLCA, HNSC, LUSC, PCM, PLMESO, UTUC.

Clinical variants and AI predictions

ClinVar

1229 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	15
Uncertain significance	524
Likely benign	445
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065490	NM_000142.5(FGFR3):c.1954A>G (p.Thr652Ala)	Pathogenic
1526266	NM_000142.5(FGFR3):c.1043C>G (p.Ser348Cys)	Pathogenic
156545	NM_000142.5(FGFR3):c.1637C>A (p.Thr546Lys)	Pathogenic
16327	NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg)	Pathogenic
16328	NM_000142.5(FGFR3):c.1138G>C (p.Gly380Arg)	Pathogenic
16329	NM_000142.5(FGFR3):c.1172C>A (p.Ala391Glu)	Pathogenic
16330	NM_000142.5(FGFR3):c.1123G>T (p.Gly375Cys)	Pathogenic
16331	NM_000142.5(FGFR3):c.1948A>G (p.Lys650Glu)	Pathogenic
16332	NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)	Pathogenic
16333	NM_000142.5(FGFR3):c.1111A>T (p.Ser371Cys)	Pathogenic
16334	NM_000142.5(FGFR3):c.2419T>G (p.Ter807Gly)	Pathogenic
16335	NM_000142.5(FGFR3):c.2419T>A (p.Ter807Arg)	Pathogenic
16336	NM_000142.5(FGFR3):c.2421A>T (p.Ter807Cys)	Pathogenic
16337	NM_000142.5(FGFR3):c.1620C>A (p.Asn540Lys)	Pathogenic
16339	NM_000142.5(FGFR3):c.746C>G (p.Ser249Cys)	Pathogenic
16341	NM_000142.5(FGFR3):c.1949A>T (p.Lys650Met)	Pathogenic
16342	NM_000142.5(FGFR3):c.1118A>G (p.Tyr373Cys)	Pathogenic
16343	t(4;14)(p16.3;q32.3)	Pathogenic
16346	NM_000142.5(FGFR3):c.1950G>T (p.Lys650Asn)	Pathogenic
16348	NM_000142.5(FGFR3):c.1948A>C (p.Lys650Gln)	Pathogenic
16351	NM_000142.5(FGFR3):c.964G>A (p.Glu322Lys)	Pathogenic
16352	NM_000142.5(FGFR3):c.850del (p.His284fs)	Pathogenic
16355	NM_000142.5(FGFR3):c.1862G>A (p.Arg621His)	Pathogenic
16356	NM_000142.5(FGFR3):c.835A>T (p.Ser279Cys)	Pathogenic
16359	NM_000142.5(FGFR3):c.1108G>T (p.Gly370Cys)	Pathogenic
1680030	NM_000142.5(FGFR3):c.791C>T (p.Thr264Met)	Pathogenic
1680033	NM_000142.5(FGFR3):c.802G>T (p.Gly268Cys)	Pathogenic
1680048	NM_000142.5(FGFR3):c.970C>G (p.Leu324Val)	Pathogenic
2582277	NM_000142.5(FGFR3):c.1910G>A (p.Gly637Glu)	Pathogenic
2582278	NM_000142.5(FGFR3):c.2089G>A (p.Gly697Ser)	Pathogenic

SpliceAI

2609 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1799253:GAA:G	acceptor_gain	1.0000
4:1799489:GCGC:G	donor_gain	1.0000
4:1799520:ACAG:A	donor_gain	1.0000
4:1801364:CA:C	acceptor_loss	1.0000
4:1801365:A:AG	acceptor_gain	1.0000
4:1801365:AG:A	acceptor_gain	1.0000
4:1801365:AGG:A	acceptor_gain	1.0000
4:1801365:AGGG:A	acceptor_gain	1.0000
4:1801366:G:GT	acceptor_gain	1.0000
4:1801366:GG:G	acceptor_gain	1.0000
4:1801366:GGG:G	acceptor_gain	1.0000
4:1801366:GGGG:G	acceptor_gain	1.0000
4:1801366:GGGGC:G	acceptor_gain	1.0000
4:1801500:G:GT	donor_gain	1.0000
4:1801526:G:GT	donor_gain	1.0000
4:1801533:CAAG:C	donor_loss	1.0000
4:1801534:AAGG:A	donor_loss	1.0000
4:1801535:AGG:A	donor_loss	1.0000
4:1801536:GG:G	donor_loss	1.0000
4:1801537:G:GA	donor_loss	1.0000
4:1801538:T:A	donor_loss	1.0000
4:1801612:C:CA	acceptor_gain	1.0000
4:1801618:A:AG	acceptor_gain	1.0000
4:1801618:AGCTG:A	acceptor_loss	1.0000
4:1801619:G:GA	acceptor_gain	1.0000
4:1801619:GC:G	acceptor_gain	1.0000
4:1801619:GCT:G	acceptor_gain	1.0000
4:1801619:GCTGC:G	acceptor_gain	1.0000
4:1801721:GAC:G	donor_gain	1.0000
4:1801734:G:GT	donor_gain	1.0000

AlphaMissense

5213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:1801442:T:C	F174S	1.000
4:1801447:T:C	C176R	1.000
4:1801483:T:A	W188R	1.000
4:1801483:T:C	W188R	1.000
4:1801484:G:C	W188S	1.000
4:1801485:G:C	W188C	1.000
4:1801485:G:T	W188C	1.000
4:1801642:T:C	L213P	1.000
4:1801669:A:T	D222V	1.000
4:1801680:T:G	Y226D	1.000
4:1801686:T:C	C228R	1.000
4:1801687:G:A	C228Y	1.000
4:1801688:C:G	C228W	1.000
4:1801732:T:C	L243P	1.000
4:1801853:C:A	P253H	1.000
4:1801913:T:C	F273S	1.000
4:1801918:T:C	C275R	1.000
4:1801919:G:A	C275Y	1.000
4:1801920:C:G	C275W	1.000
4:1801954:T:A	W287R	1.000
4:1801954:T:C	W287R	1.000
4:1801955:G:C	W287S	1.000
4:1801956:G:C	W287C	1.000
4:1801956:G:T	W287C	1.000
4:1801958:T:C	L288P	1.000
4:1803770:T:G	Y337D	1.000
4:1803776:T:C	C339R	1.000
4:1803778:C:G	C339W	1.000
4:1803790:T:A	N343K	1.000
4:1803790:T:G	N343K	1.000

dbSNP variants (sampled 300 via entrez): RS10003799 (4:1792604 G>A,C), RS1000450806 (4:1803976 C>G,T), RS1000480490 (4:1795899 C>A,G,T), RS1000683391 (4:1803145 C>G,T), RS1000692934 (4:1805872 A>G), RS1000850524 (4:1796897 G>C), RS1000946187 (4:1791901 C>G,T), RS1000977173 (4:1792145 A>G), RS1000980617 (4:1795131 G>A), RS1001139585 (4:1798447 C>G,T), RS1001186336 (4:1804640 TCTC>T), RS1001267196 (4:1807960 C>T), RS10012764 (4:1792553 C>G,T), RS1001428217 (4:1804665 G>A), RS1001467834 (4:1798524 C>T)

Disease associations

OMIM: gene MIM:134934 | disease phenotypes: MIM:187600, MIM:270230, MIM:616482, MIM:100800, MIM:109800, MIM:603956, MIM:114500, MIM:146000, MIM:149730, MIM:162900, MIM:187601, MIM:273300, MIM:602849, MIM:610474, MIM:612247, MIM:123100, MIM:254500, MIM:620192, MIM:182000, MIM:150250, MIM:101400, MIM:123500, MIM:236000

GenCC curated gene-disease

Disease	Classification	Inheritance
achondroplasia	Definitive	Autosomal dominant
hypochondroplasia	Definitive	Autosomal dominant
thanatophoric dysplasia type 1	Definitive	Autosomal dominant
Muenke syndrome	Definitive	Autosomal dominant
camptodactyly-tall stature-scoliosis-hearing loss syndrome	Definitive	Autosomal dominant
Crouzon syndrome-acanthosis nigricans syndrome	Definitive	Autosomal dominant
thanatophoric dysplasia type 2	Definitive	Autosomal dominant
lacrimoauriculodentodigital syndrome 2	Definitive	Autosomal dominant
severe achondroplasia-developmental delay-acanthosis nigricans syndrome	Strong	Autosomal dominant
LADD syndrome	Supportive	Autosomal dominant
isolated plagiocephaly	Supportive	Autosomal dominant
isolated brachycephaly	Supportive	Autosomal dominant
LADD syndrome 1	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (7)

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

Disease	Classification	Inheritance
achondroplasia	Definitive	AD
hypochondroplasia	Definitive	AD
thanatophoric dysplasia	Definitive	AD
camptodactyly-tall stature-scoliosis-hearing loss syndrome	Moderate	SD
Crouzon syndrome-acanthosis nigricans syndrome	Definitive	AD
severe achondroplasia-developmental delay-acanthosis nigricans syndrome	Moderate	AD
Muenke syndrome	Definitive	AD

Mondo (46): thanatophoric dysplasia type 1 (MONDO:0008546), severe achondroplasia-developmental delay-acanthosis nigricans syndrome (MONDO:0014658), achondroplasia (MONDO:0007037), intellectual disability (MONDO:0001071), urinary bladder cancer (MONDO:0001187), cervical cancer (MONDO:0002974), colorectal cancer (MONDO:0005575), hypochondroplasia (MONDO:0007793), LADD syndrome (MONDO:0007872), nevus, epidermal (MONDO:0008093), thanatophoric dysplasia type 2 (MONDO:0008547), testicular germ cell tumor (MONDO:0010108), Muenke syndrome (MONDO:0011274), camptodactyly-tall stature-scoliosis-hearing loss syndrome (MONDO:0012504), Crouzon syndrome-acanthosis nigricans syndrome (MONDO:0012833)

Orphanet (33): Thanatophoric dysplasia type 1 (Orphanet:1860), Thanatophoric dysplasia (Orphanet:2655), Severe achondroplasia-developmental delay-acanthosis nigricans syndrome (Orphanet:85165), Achondroplasia (Orphanet:15), Lacrimoauriculodentodigital syndrome (Orphanet:2363), Germ cell tumor of testis (Orphanet:363504), Hypochondroplasia (Orphanet:429), Muenke syndrome (Orphanet:53271), Woolly hair nevus (Orphanet:79414), Camptodactyly-tall stature-scoliosis-hearing loss syndrome (Orphanet:85164), Crouzon syndrome-acanthosis nigricans syndrome (Orphanet:93262), Thanatophoric dysplasia type 2 (Orphanet:93274), Craniosynostosis (Orphanet:1531), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

338 total (30 of 338 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000089	Renal hypoplasia
HP:0000098	Tall stature
HP:0000126	Hydronephrosis
HP:0000131	Uterine leiomyoma
HP:0000164	Abnormality of the dentition
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000217	Xerostomia
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000242	Parietal bossing
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000262	Turricephaly
HP:0000270	Delayed cranial suture closure
HP:0000272	Malar flattening
HP:0000274	Small face
HP:0000286	Epicanthus

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000639_2	Urinary bladder cancer	1.000000e-11
GCST000842_6	Bladder cancer	4.000000e-13
GCST002240_3	Bladder cancer	7.000000e-25
GCST006585_1715	Blood protein levels	7.000000e-10
GCST009391_188	Metabolite levels	3.000000e-06
GCST90020028_1705	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010482	gamma-aminoisobutyric acid measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (23)

Descriptor	Name	Tree numbers
D000130	Achondroplasia	C05.116.099.343.110; C05.116.099.708.017; C16.320.240.500
D003240	Connective Tissue Diseases	C17.300
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
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D006222	Hamartoma	C04.445
D018197	Hepatoblastoma	C04.557.435.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D017492	Keratosis, Seborrheic	C17.800.428.580
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D012509	Sarcoma	C04.557.450.795
D013736	Testicular Neoplasms	C04.588.322.762; C04.588.945.440.915; C12.100.500.260.937; C12.200.294.260.937; C12.200.758.409.937; C12.900.619.937; C19.344.762; C19.391.829.782
D013796	Thanatophoric Dysplasia	C05.116.099.343.110.500; C05.116.099.708.017.500; C05.660.585.984; C16.131.621.585.984; C16.320.240.500.500; C16.614.890
C537975	CATSHL syndrome (supp.)
C567382	Crouzon Syndrome With Acanthosis Nigricans (supp.)
C580062	Epidermal Nevus (supp.)
C562937	Hypochondroplasia (supp.)
C538132	Lacrimoauriculodentodigital syndrome (supp.)
C580241	Larsen Syndrome (supp.)
C537369	Muenke Syndrome (supp.)
C563236	Testicular Germ Cell Tumor (supp.)
C536508	Thanatophoric dysplasia, type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095217 (PROTEIN FAMILY), CHEMBL2742 (SINGLE PROTEIN), CHEMBL5291680 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

64 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 309,988 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
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
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4
CHEMBL223360	LINIFANIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL124660	TANDUTINIB	2
CHEMBL1230609	FORETINIB	2

Clinical evidence (CIViC)

Drug × variant × indication: 42 predictive associations from 45 curated evidence items; also 35 functional, 35 oncogenic, 2 diagnostic, 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FGFR3 G370C	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7307
FGFR3 Mutation	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7422
FGFR3 R248C	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7305
FGFR3 S249C	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7306
FGFR3 Y373C	Erdafitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC A	EID7308
FGFR3 S249C	Erdafitinib	Urothelial Carcinoma	Sensitivity/Response	CIViC B	EID12953 +1
FGFR3 G370C	Infigratinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID6414
FGFR3 Mutation	Erdafitinib	Bladder Urothelial Carcinoma	Sensitivity/Response	CIViC B	EID10397
FGFR3 Mutation	Infigratinib	Bladder Carcinoma	Sensitivity/Response	CIViC B	EID1910
FGFR3 Mutation	Cisplatin + Gemcitabine	Urinary Bladder Cancer	Sensitivity/Response	CIViC B	EID7566
FGFR3 R248C	Infigratinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID6410
FGFR3 R248C	Infigratinib	Bladder Carcinoma	Sensitivity/Response	CIViC B	EID8318
FGFR3 S249C	Infigratinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID6404
FGFR3 S249C	Pazopanib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID1603 +1
FGFR3 Y373C	Infigratinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID6411 +1
FGFR3 A391E	AZD-4547	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID8315
FGFR3 Amplification	Pazopanib	Ewing Sarcoma	Sensitivity/Response	CIViC C	EID7835
FGFR3 Amplification	Pazopanib	Breast Cancer	Sensitivity/Response	CIViC C	EID7955
FGFR3 G380R	Infigratinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID6413
FGFR3 R248C	Dovitinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID8319
FGFR3 S249C	Futibatinib	Urothelial Carcinoma	Sensitivity/Response	CIViC C	EID11635
FGFR3 S249C	AZD-4547	Renal Pelvis Transitional Cell Carcinoma	Sensitivity/Response	CIViC C	EID8316
FGFR3 V555M	Infigratinib	Transitional Cell Carcinoma	Resistance	CIViC C	EID6406
FGFR3 K650E	R3Mab	Multiple Myeloma	Sensitivity/Response	CIViC D	EID10365
FGFR3 K650E	Midostaurin	Multiple Myeloma	Sensitivity/Response	CIViC D	EID10407
FGFR3 Overexpression	R3Mab	Cancer	Sensitivity/Response	CIViC D	EID10352
FGFR3 Overexpression	R3Mab	Multiple Myeloma	Sensitivity/Response	CIViC D	EID10364
FGFR3 Overexpression	Dovitinib	Multiple Myeloma	Sensitivity/Response	CIViC D	EID12294
FGFR3 Overexpression	PD173074 + Dovitinib + Tyrosine Kinase Inhibitor SU5402	Bladder Carcinoma	Sensitivity/Response	CIViC D	EID803
FGFR3 S249C	Erdafitinib	Bladder Urothelial Carcinoma	Sensitivity/Response	CIViC D	EID12954

+12 more predictive associations (showing top 30 by evidence level).

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (26 total), top 25:

Ligand	Action	Affinity	Parameter
TYRA-200	Inhibition	10.0	pKd
futibatinib	Inhibition	9.3	pIC50
infigratinib	Inhibition	9.0	pIC50
ASP5878	Inhibition	8.68	pIC50
compound 29 [PMID: 36356320]	Inhibition	8.57	pIC50
dovitinib	Inhibition	8.52	pIC50
erdafitinib	Inhibition	8.52	pIC50
tinengotinib	Inhibition	8.46	pIC50
segigratinib	Inhibition	8.44	pIC50
PRN1371	Inhibition	8.39	pIC50
derazantinib	Inhibition	8.35	pIC50
vepugratinib	Inhibition	8.3	pIC50
fexagratinib	Inhibition	8.3	pIC50
tasurgratinib	Inhibition	8.27	pIC50
compound 7 [Nguyen et al., 2023]	Inhibition	8.25	pIC50
fanregratinib	Inhibition	8.22	pIC50
LY2874455	Inhibition	8.19	pIC50
dabogratinib	Inhibition	7.96	pIC50
zoligratinib	Inhibition	7.66	pIC50
rogaratinib	Inhibition	7.61	pIC50
MK-2461	Inhibition	7.3	pIC50
pemigatinib	Inhibition	7.0	pIC50
nintedanib	Inhibition	6.97	pIC50
compound 1d [PMID: 21493067]	Inhibition	6.94	pIC50
BLU-9931	Inhibition	6.82	pIC50

Binding affinities (BindingDB)

1204 measured of 1827 human assays (1827 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[(2-Aminoethoxy)methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,14][1,2,4]-triazin-4-amine dihydrochloride	IC50	0.2 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-6-[(4-methylpiperazin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.3 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[5-[(2,5-dimethylpyrrolidin-1-yl)methyl]-1H-indol-2-yl]methanone	IC50	0.32 nM	US-8829199: Aminopyrazole derivative
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
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
1-[3-[7-[6-[(1-hydroxy-2-methylpropan-2-yl)amino]pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.447 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
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
1-[3-[7-(4-imidazol-1-ylpyrimidin-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.46 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[6-(3-hydroxypiperidin-1-yl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.484 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(1-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.49 nM	US-8895745: Bicyclic heterocyclic compounds as FGFR inhibitors
1-[3-[7-[5-(cyclopropylamino)-1,3,4-thiadiazol-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.5 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
6-(ethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.5 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-6-(1,3-oxazol-5-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.5 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
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
1-[3-[7-[6-(3-oxopiperazin-1-yl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.53 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[6-(4-aminopiperidin-1-yl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.535 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(5-amino-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.54 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-(oxolan-3-yl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.542 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.545 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(6-piperidin-1-ylpyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.55 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
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
1-[3-[7-[6-(4-acetylpiperazin-1-yl)-3-pyridinyl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.56 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[6-(2-hydroxyethylamino)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.569 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(1-piperidin-4-ylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.57 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-(1-ethylpyrrolidin-3-yl)imino-3-iminopropan-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.582 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
5-(7-Methoxy-5-methyl-1-benzothiophen-2-yl)-6-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine trihydrochloride	IC50	0.6 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
4-{[4-Amino-5-(5-chloro-7-methoxy-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]methyl}-piperazin-2-one	IC50	0.6 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
1-[3-[7-(1-pyrrolidin-3-ylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.603 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-imino-3-(1-methylpiperidin-3-yl)iminopropan-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.61 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[6-(dimethylamino)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.61 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(1-piperidin-3-ylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.612 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-imino-3-(1-propan-2-ylazetidin-3-yl)iminopropan-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.613 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[(Z)-1-amino-4-imino-4-morpholin-4-ylbut-1-enyl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.64 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[5-(2-methoxyethyl)-1,3,4-thiadiazol-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.643 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
[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
1-[3-[7-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.675 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
N-(3,5-dimethoxyphenyl)-7-(1-methylpyrazol-4-yl)-N-piperidin-4-yl-1,5-naphthyridin-2-amine	IC50	0.676 nM	US-9757364: Naphthyridine derivative compounds
6-(cyclopropylmethoxymethyl)-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)-7-(piperazin-1-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.7 nM	US-9206184: Disubstituted benzothienyl-pyrrolotriazines and uses thereof
N-{[4-Amino-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]-methyl}acetamide	IC50	0.7 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
6-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-5-(7-methoxy-5-methyl-1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	IC50	0.7 nM	US-9598416: Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment cancer
1-[3-[7-[5-(2-piperidin-1-ylethyl)-1,3,4-thiadiazol-2-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.704 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[5-(2-hydroxyethyl)-2-pyridinyl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.704 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[1-(2-hydroxyethyl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.704 nM	US-8895745: Bicyclic heterocyclic compounds as FGFR inhibitors
1-[3-[7-[6-(methylamino)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.71 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-[6-(azetidin-1-yl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.715 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
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
1-[3-[7-[6-[(1-methylpiperidin-4-yl)amino]pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.73 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
2-[[3-imino-2-[3-[3-(2,2,2-trifluoroethylcarbamoylamino)phenyl]imidazo[1,2-a]pyridin-7-yl]propylidene]amino]-N,N,2-trimethylpropanamide	IC50	0.74 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases
1-[3-[7-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.78 nM	US-8895745: Bicyclic heterocyclic compounds as FGFR inhibitors
1-[3-[7-(5-amino-2-pyridinyl)imidazo[1,2-a]pyridin-3-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea	IC50	0.789 nM	US-8796244: Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases

ChEMBL bioactivities

4156 potent at pChembl≥5 of 4181 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.18	IC50	0.066	nM	ERDAFITINIB
10.00	IC50	0.1	nM	CHEMBL3701266
10.00	IC50	0.1	nM	PEMIGATINIB
10.00	IC50	0.1	nM	CHEMBL3701241
9.70	IC50	0.2	nM	CHEMBL3701239
9.70	IC50	0.2	nM	CHEMBL3937124
9.70	IC50	0.2	nM	CHEMBL5175256
9.67	IC50	0.212	nM	CHEMBL4577380
9.58	IC50	0.2645	nM	CHEMBL4568760
9.57	IC50	0.27	nM	CHEMBL4870179
9.54	IC50	0.2885	nM	CHEMBL4461304
9.54	IC50	0.29	nM	LY-2874455
9.52	IC50	0.3	nM	CHEMBL3701241
9.52	IC50	0.3	nM	CHEMBL6168351
9.51	IC50	0.31	nM	ERDAFITINIB
9.49	IC50	0.32	nM	FUTIBATINIB
9.43	IC50	0.3731	nM	CHEMBL4443370
9.42	IC50	0.3802	nM	CHEMBL3978754
9.41	IC50	0.389	nM	CHEMBL3976275
9.41	IC50	0.389	nM	CHEMBL3942763
9.40	IC50	0.4	nM	CHEMBL190161
9.40	IC50	0.4	nM	CHEMBL5203027
9.40	IC50	0.4	nM	PEMIGATINIB
9.39	IC50	0.4113	nM	CHEMBL4577380
9.39	IC50	0.41	nM	CHEMBL4529789
9.39	IC50	0.4081	nM	CHEMBL4443370
9.38	IC50	0.42	nM	ERDAFITINIB
9.37	IC50	0.43	nM	FUTIBATINIB
9.35	IC50	0.4467	nM	CHEMBL3921618
9.35	IC50	0.447	nM	CHEMBL3690444
9.34	IC50	0.4571	nM	CHEMBL3961923
9.34	IC50	0.46	nM	CHEMBL3690562
9.34	IC50	0.46	nM	CHEMBL5177696
9.33	IC50	0.47	nM	ASP-5878
9.32	IC50	0.48	nM	CHEMBL4529789
9.31	IC50	0.4898	nM	CHEMBL3937972
9.31	IC50	0.484	nM	CHEMBL3690492
9.31	IC50	0.49	nM	CHEMBL3647342
9.31	IC50	0.49	nM	CHEMBL4862823
9.31	IC50	0.49	nM	FUTIBATINIB
9.30	IC50	0.5	nM	CHEMBL191023
9.30	IC50	0.5	nM	CHEMBL191070
9.30	IC50	0.5	nM	CHEMBL3694646
9.30	IC50	0.5	nM	FUTIBATINIB
9.30	IC50	0.5	nM	CHEMBL3701262
9.30	IC50	0.5	nM	CHEMBL3911335
9.30	IC50	0.5	nM	CHEMBL4294625
9.30	IC50	0.5	nM	CHEMBL5180631
9.30	IC50	0.5	nM	CHEMBL5200643
9.30	IC50	0.5	nM	CHEMBL5592900

PubChem BioAssay actives

854 with measured affinity, of 2455 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
Pemigatinib	2141009: Inhibition of human recombinant FGFR3 by enzymatic 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	1298526: Inhibition of FGFR3 in human RT112 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0002	uM
2-methyl-6-(6-morpholin-4-yl-3H-imidazo[4,5-c]pyridin-2-yl)-7-[[(1S)-1-pyrimidin-2-ylethyl]amino]-4H-pyrazolo[4,3-b]pyridin-5-one	1601499: Inhibition of human FGFR3 V555M mutant using FL-peptide substrate measured after 45 mins in presence of ATP by mobility shift assay	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	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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
2-methyl-6-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-7-[[(1S)-2-methyl-1-pyridin-2-ylpropyl]amino]-4H-pyrazolo[4,3-b]pyridin-5-one	1601499: Inhibition of human FGFR3 V555M mutant using FL-peptide substrate measured after 45 mins in presence of ATP by mobility shift assay	ic50	0.0003	uM
2-methyl-6-(6-methyl-5-morpholin-4-yl-1H-benzimidazol-2-yl)-7-[[(1S)-1-pyrimidin-2-ylpropyl]amino]-4H-pyrazolo[4,3-b]pyridin-5-one	1601499: Inhibition of human FGFR3 V555M mutant using FL-peptide substrate measured after 45 mins in presence of ATP by mobility shift assay	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	1939968: Inhibition of human recombinant FGFR3	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	1936395: Inhibition of FGFR3 (unknown origin) using TK as substrate incubated for 1 hr in presence of biotin/ATP by HTRF assay	ic50	0.0003	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	1751595: Inhibition of human FGFR3 using biotinylated-EQEDEPEGDYFEWLE peptide as substrate incubated for 1 hr in presence of ATP by FRET assay	ic50	0.0003	uM
6-(4-fluoro-6-morpholin-4-yl-1H-benzimidazol-2-yl)-2-methyl-7-[[(1S)-1-pyrimidin-2-ylethyl]amino]-4H-pyrazolo[4,3-b]pyridin-5-one	1601499: Inhibition of human FGFR3 V555M mutant using FL-peptide substrate measured after 45 mins in presence of ATP by mobility shift assay	ic50	0.0004	uM
6-[6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-1H-benzimidazol-2-yl]-2-methyl-7-[[(1S)-1-pyrimidin-2-ylethyl]amino]-4H-pyrazolo[4,3-b]pyridin-5-one	1601498: Inhibition of human FGFR3 wild-type using FL-peptide substrate measured after 50 mins in presence of ATP by mobility shift assay	ic50	0.0004	uM
N-methyl-5-[5-[(3S)-oxolan-3-yl]oxy-6-(1-propan-2-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-3-carboxamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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
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
Erdafitinib	1897371: Inhibition of FGFR3 (unknown origin)	ic50	0.0004	uM
5-[5-[(3S)-oxolan-3-yl]oxy-6-(1-propan-2-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(trideuteriomethyl)pyridine-3-carboxamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0005	uM
4-[2-(2,6-dichloro-3,5-dimethoxyanilino)-3-pyridinyl]-N-(1-piperidin-4-ylpyrazol-4-yl)-1,3,5-triazin-2-amine	1880029: Inhibition of FGFR3 K650E 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	1880023: Inhibition of wild-type FGFR3 (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	1880029: Inhibition of FGFR3 K650E mutant (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	1880029: Inhibition of FGFR3 K650E mutant (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	1880029: Inhibition of FGFR3 K650E mutant (unknown origin) by radiometric kinase activity assay	ic50	0.0005	uM
N-methyl-3-[7-(1-methylpyrazol-4-yl)-6-[(3S)-oxolan-3-yl]oxyimidazo[1,2-b]pyridazin-3-yl]benzamide	1849313: Inhibition of recombinant human FGFR3 V555L mutant 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	0.0005	uM
3-[2-(1-cyclobutyl-6-fluorobenzimidazol-5-yl)ethynyl]-1-[(3S,5R)-5-(methoxymethyl)-1-prop-2-enoylpyrrolidin-3-yl]-5-(methylamino)pyrazole-4-carboxamide	2099585: Inhibition of FGFR3 K650M mutant (unknown origin) using 5-FAM-KKKKEEIYFFF-CONH2 peptide as fluorogenic substrate incubated for 80 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ic50	0.0005	uM
7-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]-N-hydroxyheptanamide	1897371: Inhibition of FGFR3 (unknown origin)	ic50	0.0005	uM
Infigratinib	1880029: Inhibition of FGFR3 K650E mutant (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
Futibatinib	1810704: Inhibition of human FGFR3 (450 to 758 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay	ic50	0.0005	uM
2-[4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]pyrimidin-2-yl]amino]pyrazol-1-yl]ethanol	1911608: Inhibition of recombinant FGFR3 (unknown origin) by mobility assay	ic50	0.0005	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	1751595: Inhibition of human FGFR3 using biotinylated-EQEDEPEGDYFEWLE peptide as substrate incubated for 1 hr in presence of ATP by FRET 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	1404633: Inhibition of human N-terminal GST-tagged FGFR3 (436 to 806 residues) cytoplasmic domain expressed in baculovirus expression system after 60 mins by off-chip mobility shift assay	ic50	0.0005	uM
N’-(3,5-dimethoxyphenyl)-N’-[2-(1-methylpyrazol-4-yl)quinoxalin-6-yl]-N-propan-2-ylethane-1,2-diamine	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0006	uM
3,4-difluoro-N-methyl-5-[7-(1-methylpyrazol-4-yl)-6-[(3S)-oxolan-3-yl]oxyimidazo[1,2-b]pyridazin-3-yl]benzamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0006	uM
4-[2-[4-[7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]quinoxalin-2-yl]pyrazol-1-yl]ethoxy]-N-hydroxybenzamide	1897371: Inhibition of FGFR3 (unknown origin)	ic50	0.0006	uM
N-[4-[[6-(3,5-dimethoxyphenyl)purin-9-yl]methyl]phenyl]prop-2-enamide	2063030: Inhibition of FGFR3 (unknown origin) by ELISA	ic50	0.0006	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide	1298526: Inhibition of FGFR3 in human RT112 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0006	uM
4-fluoro-N,3-dimethyl-5-[7-(1-methylpyrazol-4-yl)-6-[(3S)-oxolan-3-yl]oxyimidazo[1,2-b]pyridazin-3-yl]benzamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0007	uM
3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea;phosphoric acid	622142: Inhibition of FGFR3 juxtamembrane domain-mediated proliferation of mouse BAF3 cells transformed with TEL-Kinase construct	ic50	0.0007	uM
7-[3,5-dimethoxy-N-[2-(propan-2-ylamino)ethyl]anilino]-3-(1-methylpyrazol-4-yl)pyrido[1,2-a]pyrimidin-4-one	1778445: Inhibition of human N-terminal GST fusion tagged FGFR3 cytoplasmic domain (436 to 806 end residues) expressed in baculovirus infected Sf21 insect cells	ic50	0.0008	uM
3-(difluoromethyl)-4-fluoro-N-methyl-5-[7-(1-methylpyrazol-4-yl)-6-[(3S)-oxolan-3-yl]oxyimidazo[1,2-b]pyridazin-3-yl]benzamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0009	uM
1-[(3S,5R)-5-(methoxymethyl)-1-prop-2-enoylpyrrolidin-3-yl]-5-(methylamino)-3-[2-(2-methyl-3H-benzimidazol-5-yl)ethynyl]pyrazole-4-carboxamide	2099583: Inhibition of wild type FGFR3 (unknown origin) using 5-FAM-KKKKEEIYFFF-CONH2 peptide as fluorogenic substrate incubated for 80 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ic50	0.0009	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	1810704: Inhibition of human FGFR3 (450 to 758 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay	ic50	0.0009	uM
2,4-difluoro-N-methoxy-5-[[5-propan-2-yl-6-(5-propan-2-yl-1,3,4-oxadiazol-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide	248140: Inhibition of FGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0010	uM
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(5-morpholin-4-yl-3-pyridinyl)ethynyl]benzamide	1435446: Inhibition of recombinant FGFR3 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0010	uM
5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]-N-[3-fluoro-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidin-2-amine	1866545: Inhibition of wild type N-terminal GST tagged FGFR3 (436 to 806 residues) (unknown origin) expressed in sf21 insect cells preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by off-chip mobility shift assay	ic50	0.0010	uM
N-methyl-5-[6-(1-methylpyrazol-4-yl)-5-(oxolan-3-yloxy)pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-3-carboxamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0010	uM
N-[4-[(E)-2-[4-(4-methylpiperazin-1-yl)-6-[(5-propan-2-yl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]ethenyl]phenyl]prop-2-enamide	1685023: Inhibition of His-tagged FGFR3 V555M mutant (unknown origin) expressed in insect cells using poly Glu-Tyr preincubated for 1 hr followed by substrate addition and measured after 1 hr by Lance Eu-W1024-antiphosphoTyrosine based TR-FRET assay	ic50	0.0010	uM
1-tert-butyl-3-[3-(3,5-dimethoxyphenyl)-7-(3-morpholin-4-ylpropylamino)-1,6-naphthyridin-2-yl]urea	248925: Inhibition of FGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0010	uM
1-tert-butyl-3-[3-(3,5-dimethoxyphenyl)-7-[3-(4-methylpiperazin-1-yl)propylamino]-1,6-naphthyridin-2-yl]urea	248925: Inhibition of FGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0010	uM
5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]-N-[3-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidin-2-amine	1866545: Inhibition of wild type N-terminal GST tagged FGFR3 (436 to 806 residues) (unknown origin) expressed in sf21 insect cells preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by off-chip mobility shift assay	ic50	0.0011	uM
N-methyl-3-[7-(1-methylpyrazol-4-yl)-6-(oxetan-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzamide	1849312: Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 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	0.0011	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	7
sodium arsenite	decreases expression, increases abundance, increases expression	5
bisphenol A	affects expression, decreases methylation, affects cotreatment, increases expression	4
(+)-JQ1 compound	decreases expression, increases expression	4
Particulate Matter	affects expression, decreases expression, increases abundance, increases expression, affects cotreatment	4
methylmercuric chloride	increases expression, affects cotreatment	3
SU 5402	affects expression, decreases reaction, increases activity, decreases activity, decreases phosphorylation	3
Arsenic	affects methylation, decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Estradiol	affects cotreatment, decreases expression, affects binding, increases expression	3
Cyclosporine	decreases expression	3
futibatinib	decreases activity	2
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects cotreatment	2
ponatinib	decreases activity	2
infigratinib	increases response to substance, decreases phosphorylation	2
Zoledronic Acid	decreases expression, increases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Copper	affects binding, increases expression, affects cotreatment, decreases expression	2
Ethinyl Estradiol	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression	2
FR900359	increases phosphorylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
kojic acid	decreases expression	1
beta-lapachone	decreases expression	1

ChEMBL screening assays

975 unique, capped per target: 948 binding, 18 functional, 9 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
CHEMBL4136631	ADMET	Inhibition of recombinant human His-tagged FGFR3 cytoplasmic domain (399 to 806 residues) expressed in baculovirus expression system using Tyr 04 as substrate measured after 1 hr by Z’-LYTE assay	Identification of an Indazole-Based Pharmacophore for the Inhibition of FGFR Kinases Using Fragment-Led de Novo Design. — ACS Med Chem Lett

Cellosaurus cell lines

80 cell lines: 45 cancer cell line, 15 finite cell line, 14 induced pluripotent stem cell, 6 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0012	LP-1	Cancer cell line	Female
CVCL_0036	RT-4	Cancer cell line	Male
CVCL_0P82	GM00711	Finite cell line	Male
CVCL_0P83	GM00712	Finite cell line	Male
CVCL_0P84	GM00713	Finite cell line	Male
CVCL_0P85	GM00714	Finite cell line	Male
CVCL_0P93	GM01422	Finite cell line	Female
CVCL_0Q06	GM08855	Finite cell line	Female
CVCL_0Q08	GM08909	Finite cell line	Male
CVCL_0Q17	GM10688	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05353192	PHASE4	UNKNOWN	A Study to Evaluate the Efficacy and Safety of Recombinant Human Growth Hormone in Children With Achondroplasia
NCT00541814	PHASE4	UNKNOWN	Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function
NCT00999258	PHASE4	UNKNOWN	Impact of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients
NCT01265615	PHASE4	COMPLETED	Paricalcitol Versus Calcitriol for the Management of Renocardiac Syndrome in Renal Transplant Patients
NCT04769778	PHASE4	UNKNOWN	Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00629993	PHASE4	TERMINATED	Dissemination of Cervical Cancer Screening to Primary Care Physicians in Underserved Communities
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00862810	PHASE4	COMPLETED	Alternate Dosing Schedules Study for HPV Vaccine
NCT00923702	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India
NCT01021904	PHASE4	UNKNOWN	Primary and Secondary Prevention of Human Papillomavirus (HPV) Disease in China
NCT01101750	PHASE4	COMPLETED	Does the HPV Vaccine Cause the Same Response in Adolescent Kidney and Liver Transplant Patients as in Healthy Controls?
NCT01173900	PHASE4	COMPLETED	Delivery, Uptake and Acceptability of HPV Vaccination in Tanzanian Girls
NCT01544478	PHASE4	COMPLETED	V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110)
NCT01895517	PHASE4	COMPLETED	CervIcal Cancer Screening Trial by Randomization of HPV Testing Intervention for Upcoming Screening （CITRUS Study）
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02296255	PHASE4	COMPLETED	Effect of HPV Vaccination on Women Aged 25 Years
NCT02629510	PHASE4	UNKNOWN	The Efficacy of Tachosil® for Prevention of Hemorrhage After Loop Electrosurgical Excisional Procedure (LEEP)
NCT03197766	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
NCT03424018	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia
NCT06164951	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia
NCT06926491	PHASE3	RECRUITING	Evaluate the Efficacy and Safety of KK8398 in Patients With Achondroplasia（AOBA Study）
NCT06455059	PHASE3	ACTIVE_NOT_RECRUITING	Interventional Study of Vosoritide for the Treatment of Children With Hypochondroplasia
NCT07073014	PHASE3	ENROLLING_BY_INVITATION	Long-Term Extension Study of Vosoritide to Treat Children With Hypochondroplasia
NCT00005010	PHASE3	COMPLETED	Prevention of Kidney Transplant Rejection
NCT00975000	PHASE3	COMPLETED	Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients
NCT01056835	PHASE3	COMPLETED	Effects of PGI2 Analogue Use on the Development of Chronic Allograft Nephropathy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00384891	PHASE3	TERMINATED	Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
NCT03335059	PHASE3	TERMINATED	Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.
NCT04534075	PHASE3	COMPLETED	Dietary Fiber During Radiotherapy - a Placebo-controlled Randomized Trial
NCT05822934	PHASE3	ACTIVE_NOT_RECRUITING	Carboplatin-gemcitabine Versus Cisplatin- Gemcitabine as Neoadjuvant Chemotherapy for Treatment of Muscle Invasive Urinary Bladder Cancer
NCT02055157	PHASE2	COMPLETED	A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia
NCT02724228	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-Term Safety, Tolerability, & Efficacy of BMN 111 in Children With Achondroplasia (ACH)