Aliases for FGFR3 Gene
External Ids for FGFR3 Gene
Previous HGNC Symbols for FGFR3 Gene
Previous GeneCards Identifiers for FGFR3 Gene
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.
GeneCards Summary for FGFR3 Gene
FGFR3 (Fibroblast Growth Factor Receptor 3) is a Protein Coding gene. Diseases associated with FGFR3 include Achondroplasia and Hypochondroplasia. Among its related pathways are RET signaling and Signaling by GPCR. 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.
UniProtKB/Swiss-Prot Summary for FGFR3 Gene
Tyrosine-protein kinase that acts as 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.
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.