Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
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
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
    EC.number 2.7.10.1
    DNA
    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
    Physical map
    LOC93202 10q26.13 thioredoxin 1 pseudogene 2 INPP5F 10q26.13 inositol polyphosphate-5-phosphatase F FLJ13081 10q26.13 hypothetical protein FLJ13081 SEC23IP 10q25-q26 SEC23 interacting protein LOC338570 10q26.13 similar to alpha NAC/1.9.2. protein LOC196051 10q26.13 hypothetical protein LOC196051 WDR11 10q26 WD repeat domain 11 FGFR2 10q26 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) ATE1 10q26.13 arginyltransferase 1 FLJ20003 10q26.13 hypothetical protein FLJ20003 TACC2 10q26 transforming, acidic coiled-coil containing protein 2 FLJ25359 10q26.13 hypothetical protein FLJ25359 PLEKHA1 10q26.3 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1 LOC387715 10 LOC387715 PRSS11 10q25.3-q26.2 protease, serine, 11 (IGF binding) LOC253436 10q26.13 hypothetical LOC253436 LOC390008 10 similar to hensin CUZD1 10q26.13 CUB and zona pellucida-like domains 1 MGC45962 10q26.13 hypothetical protein MGC45962 LOC118670 10q26.13 similar to hypothetical protein MGC45962 FLJ13490 10q26.13 hypothetical protein FLJ13490 MGC35392 10q26.13 hypothetical protein MGC35392 PEGASUS 10q26 zinc finger protein, subfamily 1A, 5 (Pegasus) ACADSB 10q25-q26 acyl-Coenzyme A dehydrogenase, short/branched chain LOC340784 10q26.13 similar to NK-type homeobox LOC387716 10 similar to Hmx2 protein LOC387717 10 LOC387717 BUB3 10q26 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast) LOC390009 10 similar to 40S ribosomal protein S26
    RNA
    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
    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
  • 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
  • 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
    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