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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
Corresponding disease
ACS1 acrocephalosyndactyly type 1
ANBXL1 Antley-Bixler syndrome 1
BBDS Bent bone dysplasia
CRS11 craniosynostosis, syndromatic 11
CRS5A craniosynostosis, syndromatic 5A
CRS6 craniosynostosis, syndromatic 6
CRS7B craniosynostosis, syndromatic 7B
CRS7C craniosynostosis, syndromatic 7C
LADD1 lacrimo-auriculo-dento-digital syndrome 1
Location 10q26.13      Physical location : 123.237.844 - 123.357.972
Synonym name
  • tyrosyl-protein kinase
  • keratinocyte growth factor receptor
  • CD332 antigen
  • FGF receptor
  • bacteria-expressed kinase
  • hydroxyaryl-protein kinase
  • protein tyrosine kinase, receptor like 14
  • Synonym symbol(s) BEK, KSAM, JWS, CEK3, CFD1, ECT1, KGFR, TK14, BFR1, CD332, BFR-1, TK25, FLJ98662
    TYPE anonymous DNA segment
    STRUCTURE 120.13 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence alternative promoter
    text structure
  • 2 mutually exclusive exons, K-SAM and BEK
  • the choice of exon IIIc in mesenchymal cells involves activation of this exon and repression of exon IIIb through intronic splicing silencers flanking FGFR2 exon IIIb
  • MAPPING cloned Y linked Y status confirmed
    TRANSCRIPTS type messenger
    text alternative splicing of FGFR2 pre-mRNA results in the mutually exclusive use of exons IIIb and IIIc, which leads to critically important differences in receptor function
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 splicing 4654 92 821 . in various epithelia, in spermatogonia, in inner retina . expressed in mesenchymal cells, and during epithelial-mesenchymal transition (EMT), is expressed in colorectal, pancreatic, bladder, cervical, and prostate cancers 2018 28930565
  • also called BEK and K-sam or variant 1, IIIc isoform
  • three Ig domains, including the IIIc-type encoded by exon 9, and the C1-type carboxyl terminus encoded by exon 20
  • required for differentiation of the simple embryonic limb ectoderm into thre complex apical ectodermal ridge epithelium
  • interaction with FGF10 for palate development
  • with FGFR1 in kidney mesenchyme, are critical for normal early renal development
  • 18 - 4657 92 822 . expressed mainly on epithelial cells, mesenchymal, spermatogonia . abundantly present in the normal pituitary gland with contrasting down-regulation in neoplastic pituitary cells . is mainly expressed in normal epithelial cells, as well as in oral mucosal, esophageal, gastric, colorectal, pancreatic, pulmonary, breast, endometrial, cervical, and prostate cancers 2018 28930565
  • also called variant 2 or K-sam-IIH1, IIIb, and BFR-1, FGFR2b, KGFR
  • three Ig domains, including the IIIb type encoded by exon 8, and the C1-type carboxyl terminus encoded by exon 20
  • required for normal function of the osteoblast lineage during both intramembrane and endochondral osteogenesis
  • an increase in FGFR2c binding to multiple FGFs results in craniosynostosis, whereas binding of mutant FGFR2c to FGF10 results in severe limb pathology
  • involved in skin homeostasis and cancer development
  • target of MAGEA3
  • FGF10/FGFR2b signaling is essential for cardiac fibroblast development and growth of the myocardium
  • its expression represents a key event regulating keratinocyte early differentiation during the switch from undifferentiated to differentiating cells
  • FGFR2b-induced phagocytosis and autophagy involve converging autophagosomal and phagosomal compartments
  • FGFR2b signalling would control the number of melanosomes in keratinocytes, determining skin pigmentation
  •      - - - 1992 1582255
    17 splicing 2781 - 769 - 2018 29068468
  • also called variant 3, FGFR2c
  • lacking exons 8-10, soluble form
  • FGFR2 maintains a niche-dependent population of self-renewing highly potent non-adherent mesenchymal progenitors through FGFR2c
  • ectopic expression of FGFR2c in normal human keratinocytes induces epithelial-mesenchymal transition and leads to invasiveness and anchorage-independent growth
  • 15 splicing 3821 - 709 - 1992 1582255
  • also called variant 4
  • truncated, lack IgIII domain
  • 17 splicing 3708 - 707 - 1992 1582255
  • also called variant 5
  • 3 Ig like domains
  • 15 splicing 4103 - 706 - 1992 1582255
    also called variant 6
    16 splicing 4306 - 705 - 1992 1582255
    also called variant 7
    17 splicing 3011 - 680 - 1992 1582255
  • also called variant 9
  • unique carboxy terminus
  • 16 - 4303 - 704 - 1992 1582255
  • also called variant 8
  • lack exon 3-4
  • 16 - 3890 - 732 - 1992 1582255
    17 - 4038 - 593 - 1992 1582255
    18 - 4648 - 819 - 1992 1582255
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthpalate  highly
    Endocrineneuroendocrinepituitary  highly Homo sapiens
     parathyroid   highly
    Hearing/Equilibriumear   highly
    Visualeyeretina    Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatogonia Homo sapiens
    cell lineage
    cell lines
    at STAGE
    Text in gonads, in the coelomic domain of XX and XY gonads and in testis cords
  • 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
    interspecies homolog to rattus Fgfr2 (97.19 pc)
    homolog to murine Fgfr2 (96.95 pc)
  • protein kinase superfamily
  • Tyr protein kinase family
  • fibroblast growth factor receptor subfamily
  • CATEGORY enzyme , signaling growth factor , receptor
        plasma membrane
    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
    text osteogenesis
    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
    small molecule
  • 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
    Other regulated by HGS (regulates the FGFR2 degradative pathway, but not its juxtanuclear recycling transport) (
    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
  • 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
    Therapy target
    anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma
    FGFR2 inhibition is a potential strategy for anti-cancer therapy by eradicating breast tumor-initiating cells
    development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification
    therapeutic target for inhibition in PDAC
  • 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