Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

FGFR3 (Fibroblast Growth Factor Receptor 3)

Written1998-02Jacky Bonaventure
Unité INSERM 393, Hopital Necker-Enfants Malades, 149 rue de Sèvres 75743, Paris Cedex 15, France

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) FGFR3
LocusID (NCBI) 2261
Atlas_Id 99
Location 4p16.3  [Link to chromosome band 4p16]
Location_base_pair Starts at 1795039 and ends at 1810599 bp from pter ( according to hg19-Feb_2009)  [Mapping FGFR3.png]
Local_order centromere - IT 15 - FGFR 3 - IDUA - MYL 5 - ZNF 141 - telomere
Fusion genes
(updated 2016)
BBS10 (12q21.2) / FGFR3 (4p16.3)ETV6 (12p13.2) / FGFR3 (4p16.3)FGFR3 (4p16.3) / AES (19p13.3)
FGFR3 (4p16.3) / BAIAP2L1 (7q21.3)FGFR3 (4p16.3) / ELAVL3 (19p13.2)FGFR3 (4p16.3) / ETV6 (12p13.2)
FGFR3 (4p16.3) / IGH (14q32.33)FGFR3 (4p16.3) / IGHG1 (14q32.33)FGFR3 (4p16.3) / TACC3 (4p16.3)
FGFR3 (4p16.3) / TPRG1 (3q28)IGH (14q32.33) / FGFR3 (4p16.3)IGHG1 (14q32.33) / FGFR3 (4p16.3)
IGL (22q11.22) / FGFR3 (4p16.3)

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

Note
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

Bibliography

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, Schröck 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
 
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
 

Citation

This paper should be referenced as such :
Jacky Bonaventure
FGFR3 (fibroblast growth factor receptor 3)
Atlas Genet Cytogenet Oncol Haematol. 1998;2(1):12-13.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/FGFRID99.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  i(4p) in myeloid malignancies
Multiple myeloma
t(4;12)(p16;p13) ETV6/FGFR3
t(4;14)(p16;q32) IGH/FGFR3 and WHSC1

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Bladder: Urothelial carcinomas
Testis: Spermatocytic seminoma
Lung: Translocations in Squamous Cell Carcinoma

External links

Nomenclature
HGNC (Hugo)FGFR3   3690
Cards
AtlasFGFRID99
Entrez_Gene (NCBI)FGFR3  2261  fibroblast growth factor receptor 3
AliasesACH; CD333; CEK2; HSFGFR3EX; 
JTK4
GeneCards (Weizmann)FGFR3
Ensembl hg19 (Hinxton)ENSG00000068078 [Gene_View]  chr4:1795039-1810599 [Contig_View]  FGFR3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000068078 [Gene_View]  chr4:1795039-1810599 [Contig_View]  FGFR3 [Vega]
ICGC DataPortalENSG00000068078
TCGA cBioPortalFGFR3
AceView (NCBI)FGFR3
Genatlas (Paris)FGFR3
WikiGenes2261
SOURCE (Princeton)FGFR3
Genomic and cartography
GoldenPath hg19 (UCSC)FGFR3  -     chr4:1795039-1810599 +  4p16.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)FGFR3  -     4p16.3   [Description]    (hg38-Dec_2013)
EnsemblFGFR3 - 4p16.3 [CytoView hg19]  FGFR3 - 4p16.3 [CytoView hg38]
Mapping of homologs : NCBIFGFR3 [Mapview hg19]  FGFR3 [Mapview hg38]
OMIM100800   109800   114500   134934   146000   149730   162900   187600   187601   273300   602849   603956   610474   612247   616482   
Gene and transcription
Genbank (Entrez)AB209441 AF238374 AF245114 AF369211 AF369212
RefSeq transcript (Entrez)NM_000142 NM_001163213 NM_022965
RefSeq genomic (Entrez)NC_000004 NC_018915 NG_012632 NT_006051 NW_004929314
Consensus coding sequences : CCDS (NCBI)FGFR3
Cluster EST : UnigeneHs.1420 [ NCBI ]
CGAP (NCI)Hs.1420
Alternative Splicing GalleryENSG00000068078
Gene ExpressionFGFR3 [ NCBI-GEO ]   FGFR3 [ EBI - ARRAY_EXPRESS ]   FGFR3 [ SEEK ]   FGFR3 [ MEM ]
Gene Expression Viewer (FireBrowse)FGFR3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2261
GTEX Portal (Tissue expression)FGFR3
Protein : pattern, domain, 3D structure
UniProt/SwissProtP22607 (Uniprot)
NextProtP22607  [Sequence]  [Exons]  [Medical]  [Publications]
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 ]   
PhosPhoSitePlusP22607
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)FGF_rcpt_fam    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom   
Domain families : Pfam (Sanger)I-set (PF07679)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam07679    pfam07714   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  TyrKc (SM00219)  
DMDM Disease mutations2261
Blocks (Seattle)FGFR3
PDB (SRS)1RY7    2LZL    4K33   
PDB (PDBSum)1RY7    2LZL    4K33   
PDB (IMB)1RY7    2LZL    4K33   
PDB (RSDB)1RY7    2LZL    4K33   
Structural Biology KnowledgeBase1RY7    2LZL    4K33   
SCOP (Structural Classification of Proteins)1RY7    2LZL    4K33   
CATH (Classification of proteins structures)1RY7    2LZL    4K33   
SuperfamilyP22607
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
STRING (EMBL)FGFR3
ZODIACFGFR3
Ontologies - Pathways
QuickGOP22607
Ontology : AmiGOMAPK cascade  skeletal system development  endochondral ossification  chondrocyte differentiation  endochondral bone growth  protein tyrosine kinase activity  protein tyrosine kinase activity  fibroblast growth factor-activated receptor activity  Ras guanyl-nucleotide exchange factor activity  protein binding  ATP binding  extracellular region  nucleus  endoplasmic reticulum  Golgi apparatus  plasma membrane  plasma membrane  integral component of plasma membrane  focal adhesion  JAK-STAT cascade  cell-cell signaling  positive regulation of cell proliferation  positive regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  cell surface  positive regulation of phospholipase activity  regulation of phosphatidylinositol 3-kinase signaling  1-phosphatidylinositol-3-kinase activity  fibroblast growth factor binding  fibroblast growth factor binding  peptidyl-tyrosine phosphorylation  transport vesicle  bone mineralization  chondrocyte proliferation  phosphatidylinositol-3-phosphate biosynthetic process  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of MAPK cascade  positive regulation of GTPase activity  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of phosphatidylinositol 3-kinase activity  protein autophosphorylation  phosphatidylinositol phosphorylation  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  phosphatidylinositol-mediated signaling  negative regulation of developmental growth  bone morphogenesis  bone morphogenesis  positive regulation of ERK1 and ERK2 cascade  bone maturation  fibroblast growth factor receptor apoptotic signaling pathway  
Ontology : EGO-EBIMAPK cascade  skeletal system development  endochondral ossification  chondrocyte differentiation  endochondral bone growth  protein tyrosine kinase activity  protein tyrosine kinase activity  fibroblast growth factor-activated receptor activity  Ras guanyl-nucleotide exchange factor activity  protein binding  ATP binding  extracellular region  nucleus  endoplasmic reticulum  Golgi apparatus  plasma membrane  plasma membrane  integral component of plasma membrane  focal adhesion  JAK-STAT cascade  cell-cell signaling  positive regulation of cell proliferation  positive regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  fibroblast growth factor receptor signaling pathway  cell surface  positive regulation of phospholipase activity  regulation of phosphatidylinositol 3-kinase signaling  1-phosphatidylinositol-3-kinase activity  fibroblast growth factor binding  fibroblast growth factor binding  peptidyl-tyrosine phosphorylation  transport vesicle  bone mineralization  chondrocyte proliferation  phosphatidylinositol-3-phosphate biosynthetic process  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of MAPK cascade  positive regulation of GTPase activity  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of phosphatidylinositol 3-kinase activity  protein autophosphorylation  phosphatidylinositol phosphorylation  phosphatidylinositol-4,5-bisphosphate 3-kinase activity  phosphatidylinositol-mediated signaling  negative regulation of developmental growth  bone morphogenesis  bone morphogenesis  positive regulation of ERK1 and ERK2 cascade  bone maturation  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 PathwaysR-HSA-5655332 Signaling by FGFR3 in disease [pathway]
REACTOME PathwaysR-HSA-1839130 Signaling by activated point mutants of FGFR3 [pathway]
REACTOME PathwaysR-HSA-2033515 t(4 [pathway]
REACTOME Pathways14) translocations of FGFR3 [pathway]
REACTOME PathwaysR-HSA-2033514 FGFR3 mutant receptor activation [pathway]
NDEx NetworkFGFR3
Atlas of Cancer Signalling NetworkFGFR3
Wikipedia pathwaysFGFR3
Orthology - Evolution
OrthoDB2261
GeneTree (enSembl)ENSG00000068078
Phylogenetic Trees/Animal Genes : TreeFamFGFR3
Homologs : HomoloGeneFGFR3
Homology/Alignments : Family Browser (UCSC)FGFR3
Gene fusions - Rearrangements
Fusion : MitelmanETV6/FGFR3 [12p13.2/4p16.3]  [t(4;12)(p16;p13)]  
Fusion : MitelmanFGFR3/AES [4p16.3/19p13.3]  [t(4;19)(p16;p13)]  
Fusion : MitelmanFGFR3/BAIAP2L1 [4p16.3/7q21.3]  [t(4;7)(p16;q22)]  
Fusion : MitelmanFGFR3/ELAVL3 [4p16.3/19p13.2]  [t(4;19)(p16;p13)]  
Fusion : MitelmanFGFR3/TACC3 [4p16.3/4p16.3]  [del(4)(p16p16)]  [t(4;4)(p16;p16)]  
Fusion : MitelmanFGFR3/TPRG1 [4p16.3/3q28]  [t(3;4)(q28;p16)]  
Fusion : MitelmanIGH/FGFR3 [14q32.33/4p16.3]  [t(11;14)(q13;q32)]  [t(14;16)(q32;q23)]  
[t(14;20)(q32;q12)]  [t(4;14)(p16;q32)]  [t(6;14)(p21;q32)]  
Fusion : MitelmanIGL/FGFR3 [22q11.22/4p16.3]  [t(4;22)(p16;q11)]  
Fusion : COSMICFGFR3 [4p16.3]  -  TACC3 [4p16.3]  [fusion_1348]  [fusion_1349]  [fusion_1350]  [fusion_1351]  [fusion_1352]  [fusion_1353]  [fusion_1354]  
[fusion_1355]  [fusion_1356]  [fusion_1357]  [fusion_1358]  [fusion_1359]  [fusion_1360]  [fusion_1361]  [fusion_1434]  [fusion_1435]  
Fusion: TCGAFGFR3 4p16.3 AES 19p13.3 PRAD
Fusion: TCGAFGFR3 4p16.3 ELAVL3 19p13.2 LGG
Fusion: TCGAFGFR3 4p16.3 TACC3 4p16.3 BLCA GBM HNSC LGG LUSC
Fusion: TCGAFGFR3 4p16.3 TPRG1 3q28 HNSC
Fusion : TICdbETV6 [12p13.2]  -  FGFR3 [4p16.3]
Fusion : TICdbFGFR3 [4p16.3]  -  BAIAP2L1 [7q21.3]
Fusion : TICdbFGFR3 [4p16.3]  -  TACC3 [4p16.3]
Polymorphisms : SNP, variants
NCBI Variation ViewerFGFR3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FGFR3
dbVarFGFR3
ClinVarFGFR3
1000_GenomesFGFR3 
Exome Variant ServerFGFR3
ExAC (Exome Aggregation Consortium)FGFR3 (select the gene name)
Genetic variants : HAPMAP2261
Genomic Variants (DGV)FGFR3 [DGVbeta]
Mutations
ICGC Data PortalFGFR3 
TCGA Data PortalFGFR3 
Broad Tumor PortalFGFR3
OASIS PortalFGFR3 [ Somatic mutations - Copy number]
Cancer Gene: CensusFGFR3 
Somatic Mutations in Cancer : COSMICFGFR3 
intOGen PortalFGFR3
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
BioMutasearch FGFR3
DgiDB (Drug Gene Interaction Database)FGFR3
DoCM (Curated mutations)FGFR3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FGFR3 (select a term)
intoGenFGFR3
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)4:1795039-1810599  ENSG00000068078
CONAN: Copy Number AnalysisFGFR3 
Mutations and Diseases : HGMDFGFR3
OMIM100800    109800    114500    134934    146000    149730    162900    187600    187601    273300    602849    603956    610474    612247    616482   
MedgenFGFR3
Genetic Testing Registry FGFR3
NextProtP22607 [Medical]
TSGene2261
GENETestsFGFR3
Huge Navigator FGFR3 [HugePedia]
snp3D : Map Gene to Disease2261
BioCentury BCIQFGFR3
ClinGenFGFR3 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2261
Chemical/Pharm GKB GenePA28129
Drug Sensitivity FGFR3
Clinical trialFGFR3
Miscellaneous
canSAR (ICR)FGFR3 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=FGFR3
Probes
ProbeFGFR3 (4p16.3) in normal cells (Bari)
Litterature
PubMed413 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFGFR3
EVEXFGFR3
GoPubMedFGFR3
iHOPFGFR3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Aug 31 17:57:00 CEST 2016

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.