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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. [provided by RefSeq, Aug 2017]
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.
FGFR3 (Fibroblast Growth Factor Receptor 3) is a Protein Coding gene. Diseases associated with FGFR3 include Achondroplasia and Hypochondroplasia. Among its related pathways are Signaling by activated point mutants of FGFR3 and PI3K/AKT activation. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is FGFR2.
Fibroblast growth factors (FGFs) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGF receptors (FGFRs) are transmembrane catalytic receptors with intracellular tyrosine kinase activity.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IDA | 11294897 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA | 21873635 |
GO:0005007 | fibroblast growth factor-activated receptor activity | IBA,IMP | 8663044 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005783 | endoplasmic reticulum | IDA | -- |
GO:0005794 | Golgi apparatus | IDA | 18061161 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | PI3K/AKT activation |
.89
|
|
5 | Downstream signaling of activated FGFR2 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001501 | skeletal system development | TAS | 8601314 |
GO:0001958 | endochondral ossification | TAS | 15748888 |
GO:0002062 | chondrocyte differentiation | TAS | 15748888 |
GO:0003416 | endochondral bone growth | TAS | 15748888 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
erdafitinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
Nintedanib | Approved | Pharma | Target, inhibitor | VEGFR, FGFR, PDGFR, and FLT3 inhibitor, Kinase Inhibitors | 139 | |
Palifermin | Approved | Pharma | Target, binder | 0 | ||
Pazopanib | Approved | Pharma | Target, inhibitor | VEFGR, c-Kit, and PDGFR inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Ponatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors, Fibroblast growth factor receptor (FGFR)inhibitors | 53 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor | 58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
ACTB-1003 | 939805-30-8 | |
AZD4547 | FGFR inhibitor | 1035270-39-3 |
BGJ398 | FGFR inhibitor ,potent and selective | 872511-34-7 |
BIBF 1120 | VEGFR/PDGF/FGFR inhibitor | 656247-17-5 |
CH5183284 (Debio-1347) | 1265229-25-1 | |
Danusertib (PHA-739358) | Pan-aurora kinase inhibitor | 827318-97-8 |
Dovitinib (TKI258) Lactate | Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR) | 915769-50-5 |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
LY2874455 | FGF/FGFR Inhibitor | 1254473-64-7 |
Nintedanib (BIBF 1120) | VEGFR/PDGFR/FGFR inhibitor | 928326-83-4 |
NVP-BGJ398 phosphate | FGFR inhibitor | 1310746-10-1 |
Pazopanib (GW-786034) | VEGFR/PDGFR/FGFR inhibitor | 635702-64-6 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
PD 161570 | 192705-80-9 | |
PD 173074 | FGFR inhibitor | 219580-11-7 |
Regorafenib | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 | 755037-03-7 |
Vandetanib (ZD6474) | VEGFR2/EGFR antagonist | 443913-73-3 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | FGFR3 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | FGFR3 33 32 |
|
OneToOne | |
dog (Canis familiaris) |
Mammalia | FGFR3 33 32 |
|
OneToOne | |
rat (Rattus norvegicus) |
Mammalia | Fgfr3 32 |
|
||
mouse (Mus musculus) |
Mammalia | Fgfr3 17 33 32 |
|
||
oppossum (Monodelphis domestica) |
Mammalia | FGFR3 33 |
|
OneToOne | |
platypus (Ornithorhynchus anatinus) |
Mammalia | FGFR3 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | FGFR3 33 32 |
|
OneToOne | |
tropical clawed frog (Silurana tropicalis) |
Amphibia | fgfr3 32 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.8760 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | fgfr3 33 32 32 |
|
OneToOne | |
fruit fly (Drosophila melanogaster) |
Insecta | htl 33 34 32 |
|
ManyToMany | |
tor 34 |
|
|
|||
btl 33 34 |
|
ManyToMany | |||
worm (Caenorhabditis elegans) |
Secernentea | egl-15 33 34 32 |
|
OneToMany | |
R151.4 34 |
|
|
|||
C24G6.2b 34 |
|
|
|||
kin-9 34 |
|
|
|||
C24G6.2a 34 |
|
|
|||
ver-2 34 |
|
|
|||
F09A5.2 34 |
|
|
|||
old-2 34 |
|
|
|||
W04G5.10 34 |
|
|
|||
kin-16 34 |
|
|
|||
old-1 34 |
|
|
|||
kin-23 34 |
|
|
|||
Y50D4B.6 34 |
|
|
|||
Y38H6C.20 34 |
|
|
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F59A3.8 34 |
|