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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
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthpalate  highly
Endocrineneuroendocrinepituitary  highly Homo sapiens
 parathyroid   highly
Hearing/Equilibriumear   highly
Skeletonaxialskullfacemaxilla 
 axialskullfacemandible 
Visualeyeretina    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Connectivebone   
Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductivespermatogonia Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
Text in gonads, in the coelomic domain of XX and XY gonads and in testis cords
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