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FLASH GENE
Symbol FGFR2 contributors: mct - updated : 26-03-2019
HGNC name fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome)
HGNC id 3689
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal peptide, three Ig-like domains
  • an acidic region between the first and second Ig loops
  • a single membrane-spanning segment
  • an intracellular split tyrosine-kinase domain
  • three immunoglobulin C2 type domains
  • a ligand (FGF)-binding D2 domain
    • HOMOLOGY
    interspecies homolog to rattus Fgfr2 (97.19 pc)
    homolog to murine Fgfr2 (96.95 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • fibroblast growth factor receptor subfamily
    • CATEGORY enzyme , signaling growth factor , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • receptor tyrosine kinase class IV, keratinocyte growth factor receptor, involved in vertebral development
  • important regulator of bone formation and osteoblast activity, playing an important role in regulation of RUNX2 function and bone formation
  • mediate two independent signaling pathways in retinal pigment epithelial cells
  • playing distinct roles in proliferation and Sertoli cell differentiation during testis development
  • FGFR2 signalling may be potentially a regulator of the NMD (nonsense-mediated decay) pathway
  • FGFR1, FGFR2, fGFR3, differentially control the normal generation of oligodendrocyte progenitor (OLP) from the embryonic ventral forebrain
  • maintains a critical balance between the proliferation and differentiation of osteoprogenitor cell
  • maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells
  • essential in sustaining the breast TIC(tumor-initiating cells) pool through promotion of self-renewal and maintenance of bipotent TICs
  • involved in the development of frontal brain regions and its impairment in cognitive and social behaviors
  • FGFR2 plays an essential role in controlling cell proliferation and differentiation, and maintaining PAX6 levels in corneal epithelium via ERK-independent pathways during embryonic development
  • region-specific requirements for FGFR2 signaling in the developing caudal Wolffian duct (WD) epithelia
  • FGFR2 regulates epithelial maturation and cell cycle progression in the urethral endoderm and in the surface ectoderm
  • FGFR2 mediated FGF signaling may play an important role in palate initiation
  • role for FGFR2 in development of the middle ear skeletal tissues, suggesting potential causes for conductive hearing loss in LADD syndrome
  • role of a TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in lung organogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text osteogenesis
    PATHWAY
    metabolism
    signaling sensory transduction/vision
  • FGFR2-RPS6KA3 signalling pathway is involved in pathophysiology of breast cancer
    • a component
  • MMP14 forms a complex with FGFR2 and ADAM9 in osteoblasts
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NCAM1
  • receptor for FGF9 in the XY gonad
  • interaction of FRS2 with wild-type receptor occurs primarily at the vesicular membrane, whereas the interaction with the P253R receptor occurs exclusively at the plasma membrane
  • MMP14 is a critical negative modulator of ADAM9 activity to maintain FGFR2 signaling in calvarial osteogenesis
  • upon stimulation, FGFR2 phosphorylates tyrosine residues on GRB2, promoting dissociation from the receptor and allowing full
  • co-localization of NCAM1 and FGFR2 in early vertebrate development with intracellular signaling pathways present to enable a cellular response
  • activation of downstream signaling, establishing a role for GRB2 as an active regulator of RTK signaling
  • GRB2 is strongly implicated in controlling FGFR2 kinase activity prior to growth factor stimulation
  • FGFR2 induces rapid but reversible NANOG repression within ES cells
  • HOXC6 play an important role in several cellular events through the regulation of its functional biological targets such as BMP7, FGFR2, and PDGFRA
  • FGFR2 serves as a scaffold for multiple components of the NFKB1 signaling complex
  • GRB2 controls FGFR2 signaling by regulating receptor kinase and PTPN11 phosphatase activity in the absence of extracellular stimulation
  • LDB1 in a complex with LMO4, supports mammary stem cells by directly targeting the FGFR2 promoter in basal cells to increase its expression
  • key roles played, on the melanosome transfer in normal skin, by FGF7 released by dermal fibroblasts and by its receptor FGFR2 expressed and activated on the epidermal keratinocytes
  • potential role for NEGR1 in regulating neurite outgrowth through the modulation of FGFR2 signaling pathway
  • FGFR2 signalling correlates with maintenance of expression of a key transcription factor for basal cell self-renewal and differentiation: SOX2
  • DDX6 protein acted as an RNA-binding protein for ERBB2 and FGFR2 mRNAs and positively regulated their post-transcriptional processes
  • NEGR1 and FGFR2 cooperatively regulate cortical development, suggesting a role for defective NEGR1-FGFR2 complex and convergent downstream ERK and AKT signalling in autism spectrum disorders
    • cell & other
    REGULATION
    Other regulated by HGS (regulates the FGFR2 degradative pathway, but not its juxtanuclear recycling transport) (
    ASSOCIATED DISORDERS
    corresponding disease(s) ACS1 , CRS5A , CRS6 , CRS7B , CRS11 , ANBXL1 , CRS7C , BSCGS , LADD1 , BBDS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in gastric carcinoma
    tumoral germinal mutation      
    mutation P253R in early-onset low-grade papillary carcinoma of the bladder associated with Apert syndrome
    tumoral     --low  
    by hypermethylation in gastric cancer cells, contributing to tumor progression
    tumoral   amplification --over  
    in breast cancer
    tumoral somatic mutation      
    in endometrial cancer
    tumoral   amplification    
    in diffuse-type gastric cancer
    constitutional   deletion    
    of either FGF9 or FGFR2 in an XY gonad resulted in up-regulation of WNT4 and male-to-female sex reversal
    constitutional     --over  
    increased FGFR2 activation during embryonic period leads to abnormal differentiation or regression of the tail bud and, in turn, sacrococcygeal eversion, in certain patients with severe syndromic craniosynostosis
    tumoral     --over  
    in pancreatic ductal adenocarcinoma (PDAC) and correlated with advanced stage cancer
    tumoral fusion      
    KLK2-FGFR2 fusion gene in metastatic prostate cancer
    Susceptibility
  • to hypospadias
  • to estrogen receptor-positive breast cancer, low-risk allele
    • Variant & Polymorphism SNP , other
  • polymorphisms increasing the risk of hypospadias
  • SNP increasing the risk of breast cancer
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveuterus
    anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma
    cancerreproductivebreast
    FGFR2 inhibition is a potential strategy for anti-cancer therapy by eradicating breast tumor-initiating cells
    cancerdigestivestomach
    development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification
    cancerendocrinepancreas
    therapeutic target for inhibition in PDAC
    ANIMAL & CELL MODELS
  • cleft palate occurred in nearly all mice homozygous for the Crouzon syndrome mutation C342Y in the mesenchymal splice form of Fgfr2
  • a soluble truncated Fgfr2 molecule encoded by a premature termination codon-containing transcript is up-regulated and persists in tissues of an Apert mouse model
  • deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis