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FLASH GENE
Symbol FGF10 contributors: mct - updated : 31-01-2016
HGNC name fibroblast growth factor 10
HGNC id 3666
Corresponding disease
ALSG aplasia of lacrymal and salivary gland
LADD3 lacrimo-auriculo-dento-digital syndrome 3
Location 5p12      Physical location : 44.305.096 - 44.388.784
Synonym name
  • keratinocyte growth factor 2
  • produced by fibroblasts of urinary bladder lamina propria
  • Synonym symbol(s) KGF2
    DNA
    TYPE functioning gene
    STRUCTURE 83.69 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure
  • enhancer containing a highly conserved ISL1 consensus binding site within the FGF10 first intron
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 627 - 208 - 1999 9916808
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
    Nervousbrainlimbic systemhippocampusdentate gyrushighly
     brainhindbraincerebellum highly
     braindiencephalonthalamus highly
    Reproductivefemale systemovaryovarian follicle highly Homo sapiensAdult
     female systemovaryovarian follicle   Homo sapiensFetal
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell
    Reproductiveoocyte Homo sapiensFetal
    Reproductiveoocyte Homo sapiensAdult
    Respiratoryalveolar cell type II
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text mesenchymal cells, lung, limbs, embryonic pancreatic mesenchyme
    developing epidermis, hair follicle
    PROTEIN
    PHYSICAL PROPERTIES Hydrophobic
    STRUCTURE
    motifs/domains
  • hydrophobic N terminal domain (40AA) serving as a signal sequence
  • a FGF domain
  • two N-glycosylation sites
  • an heparin binding site and several phosphorylation sites
  • conjugated GlycoP , RiboP
    HOMOLOGY
    interspecies homolog to rattus Fgf10 (100.00 pc)
    homolog to murine Fgf10 (94.69 pc)
    intraspecies paralog to FGF7
    Homologene
    FAMILY
  • heparin-binding growth factors family
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • initiation and growth of the limb bud
  • triggering FGF8 expression in ectoderm and SHH expression in mesoderm
  • regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (FGFR2)
  • stimulating wound healing
  • essential regulator of lung and limb formation
  • role in prostatic development, morphogenesis and epithelial proliferation, adipogenesis
  • promoting the proliferation of embryonic pancreatic epithelial cells
  • regulates the morphogenesis of the hepatopancreatic duct and intestinal tube
  • regulating G1 cyclins and CDKs
  • promotes invasion and outgrowth of trophoblasts and it increases SPRY2 expression, which attenuates trophoblast sprouting
  • implicated in control of neurogenesis
  • controls the patterning of the tracheal cartilage rings via SHH
  • potentially regulating Meckel cartilage formation during early mandibular morphogenesis by controlling the cell differentiation in the lateral area of the mandibular process
  • FGF3 and FGF10 are not required for specification of cardiovascular progenitors, but rather for their normal developmental coordination
  • likely functional network involving BARX2, FGF10 and MMPs that plays an essential role in regulating branching morphogenesis of the ocular glands
  • may contribute to human preantral follicle development.
  • FGF8 and FGF10 promotes the proliferation of the cardiac progenitor cells that form the arterial pole of the heart
  • FGF10 and FGF3 secreted from the forming neurohypophysis exert direct guidance effects on hypothalamic neurosecretory axons
  • prevents the differentiation of distal epithelial progenitors into SOX2-expressing airway epithelial cells
  • FGF7 and FGF10 are involved in the proliferation of ameloblastoma cells through the MAPK pathway
  • SDC4 participates likely in amelogenesis, and FGF10 may modulate dental epithelial cell behaviors through the regulation of SDC4 expression
  • regulates regional cardiomyocyte proliferation in the fetal heart, and triggers cell-cycle re-entry of adult cardiomyocytes
  • neuroprotective function of FGF10 against ischemic neuronal injury
  • dual role for FGF10 in cochlear development, to regulate outgrowth of the duct and subsequently as a bidirectional signal that sequentially specifies Reissner membrane and outer sulcus non-sensory domains
  • involvement in breast tumorigenesis
  • role of a TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in lung organogenesis
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
  • FGF10/FGFR2b signaling is essential for cardiac fibroblast development and growth of the myocardium
  • DLX5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand for FGFR2 receptor
  • CEBP in adipocytes
  • upregulating Na, K-ATPase via thr MAPK pathway
  • interacting with FGFR2B for palate development(coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an FGF-SHH signaling network)
  • interacting with FGFBP1
  • key role for FGF3, and a secondary role for FGF10, in WNT8A expression
  • interacting with cortactin (involved in keratinocyte migration promoted by both FGF7 and FGF10)
  • ELAVL1 bind and control the FGF10 and TBX4 mRNAs
  • BARX2 and FGF10 cooperate in the regulation of MMPs)
  • ISL1 directly regulates FGF10 transcription during human cardiac outflow formation
  • TBX4 and TBX5 interact with FGF10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development
  • inhibition of FGF10 by inflammatory signaling involves the NFKB1-dependent interactions between RELA, SP3, and the FGF10 promoter
  • PBX1 directly binds to the FGF10 promoter and cooperates with MEIS and HOX proteins to transcriptionally activate FGF10
  • ETV1 and EWSR1 transactivate FGF10 directly and cooperatively in response to apical ectodermal ridge (AER)-FGFs
  • LHX9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme
  • glycoprotein that specifically binds to FGFR2 to control signaling pathways including cell differentiation, proliferation, and apoptosis
  • TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds
  • cell & other
    REGULATION
    activated by GATA3 that directly activates FGF10 in the early inner ear, and does so through a single binding site
    ASSOCIATED DISORDERS
    corresponding disease(s) ALSG , LADD3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in &8764;10p100 of breast cancers and increased levels of FGF10 are highly correlated with proliferation rate of breast cancer cell lines and cancer cell invasion
    Susceptibility
  • to chronic obstructive pulmonary disease (COPD)
  • to lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD)spectrum
  • Variant & Polymorphism other
  • FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD
  • SNVs or CNVs involving FGF10 loci in our subjects with lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD)spectrum
  • Candidate gene candidate gene in patients with anorectal malformations and exstrophy of the cloaca
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheroma 
    may be a promising agent for treatment of ischemic stroke
    cardiovascularaquired 
    potential target for cardiac repair
    ANIMAL & CELL MODELS
  • defective terminal differentiation and hypoplasia of
  • epidermis in Fgf10(-/-) mouse
  • overexpression of Fgf10 in adult mice promotes cardiomyocyte but not cardiac fibroblast cell-cycle re-entry