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FLASH GENE
Symbol FGF18 contributors: mct/npt/pgu - updated : 11-04-2013
HGNC name fibroblast growth factor 18
HGNC id 3674
Location 5q35.1      Physical location : 170.846.666 - 170.884.621
Synonym symbol(s) FGF-18, ZFGF5
DNA
TYPE functioning gene
STRUCTURE 37.51 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • containing putative Tcf4-binding motifs
  • two transcription pathways that are essential for bone, physically and functionally converge at the promoter (direct interactions of Runx2 and canonical Wnt signaling induce FGF18)
  • a GLIS3 binding site in the FGF18 promoter flanking region is important in its regulation by GLIS3
  • MAPPING cloned Y linked N status confirmed
    Physical map
    FLJ20364 5q35.1 hypothetical protein FLJ20364 DOCK2 5q35.1 dedicator of cyto-kinesis 2 FOXI1 5q34 forkhead box I1 LOC345430 5q35.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC133874 5q35.1 hypothetical gene LOC133874 LCP2 5q34 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) KCNMB1 5q34 potassium large conductance calcium-activated channel, subfamily M, beta member 1 KCNIP1 5q35.2 Kv channel interacting protein 1 LOC389343 5 LOC389343 GABRP 5q33-q34 gamma-aminobutyric acid (GABA) A receptor, pi RANBP17 5q31 RAN binding protein 17 USP12P1 5q33-q34 ubiquitin specific protease 12 pseudogene 1 TLX3 5q35.1 T-cell leukemia, homeobox 3 LOC391847 5 similar to hypothetical protein LOC391848 5 similar to 60S ribosomal protein L10 (QM protein homolog) NPM1 5q35 nucleophosmin (nucleolar phosphoprotein B23, numatrin) FGF18 5q34 fibroblast growth factor 18 FBXW1B 5q35.1 F-box and WD-40 domain protein 1B STK10 5q35.1 serine/threonine kinase 10 LOC285588 5q35.2 similar to RIKEN cDNA 1700007I06 DC-UbP 5q35.2 dendritic cell-derived ubiquitin-like protein KIAA1295 5q35.2 KIAA1295 protein LOC391849 5 similar to neuralized homolog LOC133539 5q35.2 similar to RIKEN cDNA 1810009O10 DUSP1 5q34 dual specificity phosphatase 1 KIAA1181 5q35.2 KIAA1181 protein LOC389344 5 LOC389344 RPL26L1 5q35.2 ribosomal protein L26-like 1 LOC285591 5q35.2 inorganic pyrophosphatase pseudogene ATP6V0E 5q35.3 ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e LOC153222 5q35.2 adult retina protein BNIP1 5q33-q34 BCL2/adenovirus E1B 19kDa interacting protein 1 LOC391850 5 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NKX2-5 5q34-q35.3 NK2 transcription factor related, locus 5 (Drosophila) STC2 5p14.2-q15 stanniocalcin 2 LOC389345 5 LOC389345 LOC91272 5q35.2 hypothetical protein BC007436
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1546 - 207 - 1998 9742123
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Reproductivefemale systemovary   
    Respiratorylung    
    Skin/Tegumentskin appendageshair    Homo sapiensAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumenthair follicle cell Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text developing tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • typical hydrophobic signal sequence at N terminus
  • HOMOLOGY
    interspecies homolog to rattus FGF18
    Homologene
    FAMILY
  • heparin-binding growth factors family
  • FGF8 subfamily
  • CATEGORY RNA associated , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • signaling molecule inducing osteoclast formation through receptor activator of nulear receptor NFKB ligand and PTGS2 resembling to FGF2 and stimulating the proliferation of chondrocytes
  • regulate the growth plate chondrocyte proliferation, hypertrophy and cartilage vascularization necessary for endochondral ossification
  • may play a prominent role in chondrogenesis and osteogenesis during skeletal development and growth
  • perichondrial FGF1, FGF2, FGF6, FGF7, FGF9, FGF18, FGF21, FGF22 regulate growth plate chondrogenesis
  • induction of hepatic and intestinal proliferation
  • repressing noggin gene induction and thereby increased chondrocyte gene expression and chondrogenesis by facilitating bone morphogenetic protein-dependent signals
  • required for embryonic lung alveolar development
  • FGF18 and FGFR3 are involved, possibly as partners, in the control of intestinal precursor cell proliferation
  • provided both directional and proliferative cues to chondrocytes in the developing upper respiratory tract (exerted this effect on developing chondrocytes by up-regulating SOX9 expression)
  • enhancing cell migration in response to mechanical damage
  • seems to play a role in maintenance of chondrocyte properties, although its expression was rather high in dedifferentiated chondrocytes
  • novel regulatory mechanism for FGF18 signaling involving GLG1 and DLK1
  • epithelial FGF18 signaling and its reduction in the milieu of hair stem cells are crucial for the maintenance of resting and growth phase, respectively
  • pleiotropic protein that stimulates proliferation in several tissues
  • could be used to improve bone repair and regeneration
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • target of the WNT signaling pathway
  • interacting with RUNX2
  • interacting with perlecan (perlecan can bind FGF18 and alter the mitogenic effect of FGF18 on growth plate chondrocytes)
  • direct target of canonical Wnt signaling
  • ligand of FGFR3
  • overexpression of WDR5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of TWIST1 and FGF18
  • GLG1 is involved in FGF18 signalling via FGFR3C
  • FOXP1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling FGF18 expression (pMID: 23946441)
  • cell & other
    REGULATION
    activated by calcineurin-dependent transcription factor, NFAT4 (nuclear factor of activated T-cell 4)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal tumours and is progressively enhanced during colon carcinogenesis reaching very high levels in carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Fgf-18 null mice exhibit a skeletal dwarfism similar to that of perlecan null mice