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FGFR3 (Fibroblast Growth Factor Receptor 3)

Identity

HGNC (Hugo) FGFR3
LocusID (NCBI) 2261
Location 4p16.3
Location_base_pair Starts at 1795039 and ends at 1810599 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere - IT 15 - FGFR 3 - IDUA - MYL 5 - ZNF 141 - telomere

DNA/RNA

 
  c-FGFR3 (4p16.3) in normal cells: PAC 1054L13 (above) and PAC 1174P18 (below) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Description 16.5 Kb; 19 exons; exon 1 unknown in human
Transcription 4.0 Kb mRNA; large 3' untranslated region (1.4 kb); alternative splicing of exons 7 and 8 gives rise to two isoforms IIIb and IIIc

Protein

 
  Protein Diagram
Description 806 amino acids; 115 kDa; tyrosine kinase receptor; contains three major domains: an extracellular domain with 3 Ig-like loops, a highly hydrophobic transmembrane domain (22 amino acids) and an intracellular domain with tyrosine kinase activity
Expression mostly in brain, cartilage, liver, inner ear, kidney
Localisation plasma membrane
Function FGF receptor with tyrosine kinase activity; binding of ligand (FGF) induces receptor dimerization, autophosphorylation and signal transduction
Homology with other FGFR (1, 2 and 4); Cek 2 in chicken

Implicated in

Entity t(4;14)(p16.3;q32.3)/multiple myeloma --> FGFR3 -IgH
Disease plasma cell leukaemia and multiple myeloma
Prognosis unknown: found in 11 cases, but with no data on clinics
Abnormal Protein no fusion protein, but promoter exchange between both partner genes
Oncogenesis overexpression and activation of FGFR 3 provides an oncogenic signal
  
Entity squeletal dysplasia (inborn diseases)
Disease hypochondroplasia, achondroplasia, thanatophoric dwarfism (TD I and II), Crouzon syndrome with acanthosis nigricans and coronal craniosynostosis; endochondral and membranous ossification defects are caused by recurrent missense mutations
  

Breakpoints

 
Note Chromosome 4 breakpoints are clustured in a 50-70 kb region centromeric to FGFR 3

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030

External links

Nomenclature
HGNC (Hugo)FGFR3   3690
Cards
AtlasFGFRID99
Entrez_Gene (NCBI)FGFR3  2261  fibroblast growth factor receptor 3
GeneCards (Weizmann)FGFR3
Ensembl (Hinxton)ENSG00000068078 [Gene_View]  chr4:1795039-1810599 [Contig_View]  FGFR3 [Vega]
ICGC DataPortalENSG00000068078
AceView (NCBI)FGFR3
Genatlas (Paris)FGFR3
WikiGenes2261
SOURCE (Princeton)NM_000142 NM_001163213 NM_022965
Genomic and cartography
GoldenPath (UCSC)FGFR3  -  4p16.3   chr4:1795039-1810599 +  4p16.3   [Description]    (hg19-Feb_2009)
EnsemblFGFR3 - 4p16.3 [CytoView]
Mapping of homologs : NCBIFGFR3 [Mapview]
OMIM100800   109800   134934   146000   149730   162900   187600   187601   273300   602849   603956   610474   612247   
Gene and transcription
Genbank (Entrez)AB209441 AF238374 AF245114 AF369211 AF369212
RefSeq transcript (Entrez)NM_000142 NM_001163213 NM_022965
RefSeq genomic (Entrez)AC_000136 NC_000004 NC_018915 NG_012632 NT_006051 NW_001838896 NW_004929314
Consensus coding sequences : CCDS (NCBI)FGFR3
Cluster EST : UnigeneHs.1420 [ NCBI ]
CGAP (NCI)Hs.1420
Alternative Splicing : Fast-db (Paris)GSHG0022405
Alternative Splicing GalleryENSG00000068078
Gene ExpressionFGFR3 [ NCBI-GEO ]     FGFR3 [ SEEK ]   FGFR3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP22607 (Uniprot)
NextProtP22607  [Medical]
With graphics : InterProP22607
Splice isoforms : SwissVarP22607 (Swissvar)
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)FGF_rcpt_3    FGF_rcpt_fam    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    Immunoglobulin    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom   
Related proteins : CluSTrP22607
Domain families : Pfam (Sanger)I-set (PF07679)    ig (PF00047)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam07679    pfam00047    pfam07714   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  TyrKc (SM00219)  
DMDM Disease mutations2261
Blocks (Seattle)P22607
PDB (SRS)1RY7    2LZL    4K33   
PDB (PDBSum)1RY7    2LZL    4K33   
PDB (IMB)1RY7    2LZL    4K33   
PDB (RSDB)1RY7    2LZL    4K33   
Human Protein AtlasENSG00000068078
Peptide AtlasP22607
HPRD00624
IPIIPI00027174   IPI00220253   IPI00220254   IPI01013721   IPI00382818   IPI00016305   IPI00945340   
Protein Interaction databases
DIP (DOE-UCLA)P22607
IntAct (EBI)P22607
FunCoupENSG00000068078
BioGRIDFGFR3
IntegromeDBFGFR3
STRING (EMBL)FGFR3
Ontologies - Pathways
QuickGOP22607
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  MAPK cascade  skeletal system development  positive regulation of endothelial cell proliferation  endochondral ossification  morphogenesis of an epithelium  chondrocyte differentiation  lens morphogenesis in camera-type eye  endochondral bone growth  protein tyrosine kinase activity  fibroblast growth factor-activated receptor activity  protein binding  ATP binding  extracellular region  nucleus  lysosome  endoplasmic reticulum  plasma membrane  integral component of plasma membrane  focal adhesion  epidermal growth factor receptor signaling pathway  JAK-STAT cascade  cell-cell signaling  positive regulation of cell proliferation  positive regulation of cell proliferation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  cytoplasmic side of plasma membrane  cell surface  positive regulation of phospholipase activity  cytoplasmic membrane-bounded vesicle  fibroblast growth factor binding  fibroblast growth factor binding  peptidyl-tyrosine phosphorylation  substantia nigra development  central nervous system myelination  bone mineralization  positive regulation of protein ubiquitination  somatic stem cell maintenance  chondrocyte proliferation  Fc-epsilon receptor signaling pathway  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of MAPK cascade  positive regulation of neuron apoptotic process  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of cell differentiation  negative regulation of mitosis  negative regulation of smoothened signaling pathway  protein autophosphorylation  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  digestive tract morphogenesis  negative regulation of developmental growth  response to axon injury  negative regulation of astrocyte differentiation  negative regulation of epithelial cell proliferation  inner ear receptor cell differentiation  bone morphogenesis  bone morphogenesis  axonogenesis involved in innervation  alveolar secondary septum development  lens fiber cell development  positive regulation of ERK1 and ERK2 cascade  bone maturation  epithelial cell fate commitment  positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway  cochlea development  positive regulation of canonical Wnt signaling pathway  fibroblast growth factor receptor apoptotic signaling pathway  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  MAPK cascade  skeletal system development  positive regulation of endothelial cell proliferation  endochondral ossification  morphogenesis of an epithelium  chondrocyte differentiation  lens morphogenesis in camera-type eye  endochondral bone growth  protein tyrosine kinase activity  fibroblast growth factor-activated receptor activity  protein binding  ATP binding  extracellular region  nucleus  lysosome  endoplasmic reticulum  plasma membrane  integral component of plasma membrane  focal adhesion  epidermal growth factor receptor signaling pathway  JAK-STAT cascade  cell-cell signaling  positive regulation of cell proliferation  positive regulation of cell proliferation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  cytoplasmic side of plasma membrane  cell surface  positive regulation of phospholipase activity  cytoplasmic membrane-bounded vesicle  fibroblast growth factor binding  fibroblast growth factor binding  peptidyl-tyrosine phosphorylation  substantia nigra development  central nervous system myelination  bone mineralization  positive regulation of protein ubiquitination  somatic stem cell maintenance  chondrocyte proliferation  Fc-epsilon receptor signaling pathway  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of MAPK cascade  positive regulation of neuron apoptotic process  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of cell differentiation  negative regulation of mitosis  negative regulation of smoothened signaling pathway  protein autophosphorylation  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  perinuclear region of cytoplasm  digestive tract morphogenesis  negative regulation of developmental growth  response to axon injury  negative regulation of astrocyte differentiation  negative regulation of epithelial cell proliferation  inner ear receptor cell differentiation  bone morphogenesis  bone morphogenesis  axonogenesis involved in innervation  alveolar secondary septum development  lens fiber cell development  positive regulation of ERK1 and ERK2 cascade  bone maturation  epithelial cell fate commitment  positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway  cochlea development  positive regulation of canonical Wnt signaling pathway  fibroblast growth factor receptor apoptotic signaling pathway  
Pathways : KEGGMAPK signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Endocytosis    PI3K-Akt signaling pathway    Regulation of actin cytoskeleton    Pathways in cancer    MicroRNAs in cancer    Bladder cancer   
REACTOMEP22607 [protein]
REACTOME PathwaysREACT_116125 Disease [pathway]
REACTOME PathwaysREACT_6900 Immune System [pathway]
REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseFGFR3
Wikipedia pathwaysFGFR3
Gene fusion - rearrangments
Rearrangement : COSMICFGFR3 [4p16.3]  -  TACC3 [4p16.3]
Rearrangement : TICdbFGFR3 [4p16.3]  -  BAIAP2L1 [6q21]
Rearrangement : TICdbFGFR3 [4p16.3]  -  TACC3 [14q11.2]
Rearrangement : TICdbETV6 [12p13.2]  -  FGFR3 [7p21.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)FGFR3
SNP (GeneSNP Utah)FGFR3
SNP : HGBaseFGFR3
Genetic variants : HAPMAPFGFR3
1000_GenomesFGFR3 
ICGC programENSG00000068078 
Cancer Gene: CensusFGFR3 
CONAN: Copy Number AnalysisFGFR3 
Somatic Mutations in Cancer : COSMICFGFR3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
DECIPHER (Syndromes)4:1795039-1810599
Mutations and Diseases : HGMDFGFR3
OMIM100800    109800    134934    146000    149730    162900    187600    187601    273300    602849    603956    610474    612247   
MedgenFGFR3
GENETestsFGFR3
Disease Genetic AssociationFGFR3
Huge Navigator FGFR3 [HugePedia]  FGFR3 [HugeCancerGEM]
Genomic VariantsFGFR3  FGFR3 [DGVbeta]
Exome VariantFGFR3
dbVarFGFR3
ClinVarFGFR3
snp3D : Map Gene to Disease2261
General knowledge
Homologs : HomoloGeneFGFR3
Homology/Alignments : Family Browser (UCSC)FGFR3
Phylogenetic Trees/Animal Genes : TreeFamFGFR3
Chemical/Protein Interactions : CTD2261
Chemical/Pharm GKB GenePA28129
Drug Sensitivity FGFR3
Clinical trialFGFR3
Cancer Resource (Charite)ENSG00000068078
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=FGFR3
Probes
ProbeFGFR3 (4p16.3) in normal cells (Bari)
Litterature
PubMed370 Pubmed reference(s) in Entrez
CoreMineFGFR3
GoPubMedFGFR3
iHOPFGFR3

Bibliography

Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.
Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A
Nature. 1994 ; 371 (6494) : 252-254.
PMID 8078586
 
FGFR activation in skeletal disorders: too much of a good thing.
Webster MK, Donoghue DJ
Trends in genetics : TIG. 1997 ; 13 (5) : 178-182.
PMID 9154000
 
Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.
Chesi M, Nardini E, Brents LA, Schrˆck E, Ried T, Kuehl WM, Bergsagel PL
Nature genetics. 1997 ; 16 (3) : 260-264.
PMID 9207791
 
A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.
Richelda R, Ronchetti D, Baldini L, Cro L, Viggiano L, Marzella R, Rocchi M, Otsuki T, Lombardi L, Maiolo AT, Neri A
Blood. 1997 ; 90 (10) : 4062-4070.
PMID 9354676
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-1998Jacky Bonaventure
Unité INSERM 393, Hopital Necker-Enfants Malades 149 rue de Sèvres 75743 Paris Cedex 15, France

Citation

This paper should be referenced as such :
Bonaventure J
FGFR3 (Fibroblast Growth Factor Receptor 3);
Atlas Genet Cytogenet Oncol Haematol. February 1998
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/FGFRID99.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Nov 8 16:25:58 CET 2014

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