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EXT2 exostoses (multiple) 2

Written2000-01Judith VMG Bovée
Afdeling Pathologie, Leids Universitair Medisch Centrum, Postbus 9600, L1-Q, 2300 RC Leiden, the Netherlands
Updated2002-03Judith VMG Bovée
Afdeling Pathologie, Leids Universitair Medisch Centrum, Postbus 9600, L1-Q, 2300 RC Leiden, the Netherlands

(Note : for Links provided by Atlas : click)

Identity

Alias_namesexostoses (multiple) 2
exostosin 2
Alias_symbol (synonym)SOTV
Other alias
HGNC (Hugo) EXT2
LocusID (NCBI) 2132
Atlas_Id 213
Location 11p11.2  [Link to chromosome band 11p11]
Location_base_pair Starts at 44095549 and ends at 44245430 bp from pter ( according to hg19-Feb_2009)  [Mapping EXT2.png]
 
  EXT2 (11p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ABI3BP (3q12.2) / EXT2 (11p11.2)ACCS (11p11.2) / EXT2 (11p11.2)CSTB (21q22.3) / EXT2 (11p11.2)
EXT2 (11p11.2) / ALKBH3 (11p11.2)EXT2 (11p11.2) / ALX4 (11p11.2)SBF2 (11p15.4) / EXT2 (11p11.2)

DNA/RNA

 
Description Sixteen exons across the EXT2 locus were identified, two of which (1a and 1b) are alternatively spliced; spans approximately 108 kb of genomic DNA
Transcription 3.5 and 3.7 kb

Protein

Description 718 amino acids; 82.2 kDa
Expression mRNA is ubiquitously expressed. In mouse embryo's, a high level of expression of Ext2 mRNA has been found in developing limb buds and expression was demonstrated to be confined to the proliferating and prehypertrophic chondrocytes of the growth plate.
Localisation endoplasmic reticulum
Function
  • a tumour suppressor function is suggested; exostosin-2 (EXT2) is an endoplasmic reticulum localized type II transmembrane glycoprotein which together with exostosin-1 (EXT1) forms a Golgi-localized hetero-oligomeric complex that catalyzes heparan sulphate (HS) polymerization.
  • It is thus hypothesized that EXT controls HSPG synthesis and display at the cell surface, which in turn is involved in FGF and IHh/PTHrP signalling within the normal growth plate.
  • Homology human EXT1, EXTL1, EXTL2 and EXTL3, mouse Ext2

    Mutations

    Germinal germline mutations in EXT2 are causative for hereditary multiple exostoses, a heterogeneous autosomal dominant disorder; mutations include nucleotide substitutions (57%), small deletions (19%) and small insertions (24%), of which the majority is predicted to result in a truncated or non-functional protein
    Somatic no somatic mutations were found in 34 sporadic and hereditary osteochondromas and secondary peripheral chondrosarcomas tested

    Implicated in

    Note
      
    Entity hereditary multiple exostoses
    Prognosis the main complication in hereditary multiple exostoses is malignant transformation of an osteochondroma (exostosis) into chondrosarcoma, which is estimated to occur in 1-3% of the HME cases
    Cytogenetics 11p rearrangement was found in 1 sporadic osteochondroma (exostosis) using cytogenetic analysis; loss of heterozygosity at the EXT2 locus was absent in 14 osteochondromas
      

    Bibliography

    EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.
    Bovée JV, Cleton-Jansen AM, Wuyts W, Caethoven G, Taminiau AH, Bakker E, Van Hul W, Cornelisse CJ, Hogendoorn PC
    American journal of human genetics. 1999 ; 65 (3) : 689-698.
    PMID 10441575
     
    Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas.
    Bridge JA, Nelson M, Orndal C, Bhatia P, Neff JR
    Cancer. 1998 ; 82 (9) : 1657-1663.
    PMID 9576285
     
    The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans.
    Clines GA, Ashley JA, Shah S, Lovett M
    Genome research. 1997 ; 7 (4) : 359-367.
    PMID 9110175
     
    Genetic heterogeneity in families with hereditary multiple exostoses.
    Cook A, Raskind W, Blanton SH, Pauli RM, Gregg RG, Francomano CA, Puffenberger E, Conrad EU, Schmale G, Schellenberg G
    American journal of human genetics. 1993 ; 53 (1) : 71-79.
    PMID 8317501
     
    Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8.
    Hecht JT, Hogue D, Strong LC, Hansen MF, Blanton SH, Wagner M
    American journal of human genetics. 1995 ; 56 (5) : 1125-1131.
    PMID 7726168
     
    The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate.
    Kitagawa H, Shimakawa H, Sugahara K
    The Journal of biological chemistry. 1999 ; 274 (20) : 13933-13937.
    PMID 10318803
     
    The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.
    Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K
    The Journal of biological chemistry. 1998 ; 273 (41) : 26265-26268.
    PMID 9756849
     
    New perspectives on the molecular basis of hereditary bone tumours.
    McCormick C, Duncan G, Tufaro F
    Molecular medicine today. 1999 ; 5 (11) : 481-486.
    PMID 10529789
     
    Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.
    Raskind WH, Conrad EU, Chansky H, Matsushita M
    American journal of human genetics. 1995 ; 56 (5) : 1132-1139.
    PMID 7726169
     
    A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses.
    Simmons AD, Musy MM, Lopes CS, Hwang LY, Yang YP, Lovett M
    Human molecular genetics. 1999 ; 8 (12) : 2155-2164.
    PMID 10545594
     
    EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.
    Stickens D, Brown D, Evans GA
    Developmental dynamics : an official publication of the American Association of Anatomists. 2000 ; 218 (3) : 452-464.
    PMID 10878610
     
    Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11.
    Wu YQ, Heutink P, de Vries BB, Sandkuijl LA, van den Ouweland AM, Niermeijer MF, Galjaard H, Reyniers E, Willems PJ, Halley DJ
    Human molecular genetics. 1994 ; 3 (1) : 167-171.
    PMID 8162019
     
    Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11.
    Wuyts W, Ramlakhan S, Van Hul W, Hecht JT, van den Ouweland AM, Raskind WH, Hofstede FC, Reyniers E, Wells DE, de Vries B
    American journal of human genetics. 1995 ; 57 (2) : 382-387.
    PMID 7668264
     
    Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.
    Wuyts W, Van Hul W
    Human mutation. 2000 ; 15 (3) : 220-227.
    PMID 10679937
     

    Citation

    This paper should be referenced as such :
    Bovée, JVMG
    EXT2 (exostoses (multiple) 2)
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):186-187.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/EXT2ID213.html
    History of this paper:
    Bovée, JVMG. EXT2 (exostoses (multiple) 2). Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):5-6.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37576/01-2000-EXT2ID213.pdf


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

    Leukemias TL_t1111p11p11ID2506


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]

    Solid Tumors TT_t0311q12p11ID105590 TT_t1111p11p11ID100463 TT_t1111p11p11ID100464


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
      Multiple osteochondromas (MO)


    External links

    Nomenclature
    HGNC (Hugo)EXT2   3513
    LRG (Locus Reference Genomic)LRG_494
    Cards
    AtlasEXT2ID213
    Entrez_Gene (NCBI)EXT2  2132  exostosin glycosyltransferase 2
    AliasesSOTV; SSMS
    GeneCards (Weizmann)EXT2
    Ensembl hg19 (Hinxton)ENSG00000151348 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000151348 [Gene_View]  ENSG00000151348 [Sequence]  chr11:44095549-44245430 [Contig_View]  EXT2 [Vega]
    ICGC DataPortalENSG00000151348
    TCGA cBioPortalEXT2
    AceView (NCBI)EXT2
    Genatlas (Paris)EXT2
    WikiGenes2132
    SOURCE (Princeton)EXT2
    Genetics Home Reference (NIH)EXT2
    Genomic and cartography
    GoldenPath hg38 (UCSC)EXT2  -     chr11:44095549-44245430 +  11p11.2   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)EXT2  -     11p11.2   [Description]    (hg19-Feb_2009)
    GoldenPathEXT2 - 11p11.2 [CytoView hg19]  EXT2 - 11p11.2 [CytoView hg38]
    ImmunoBaseENSG00000151348
    Mapping of homologs : NCBIEXT2 [Mapview hg19]  EXT2 [Mapview hg38]
    OMIM133701   608210   616682   
    Gene and transcription
    Genbank (Entrez)AK296713 AK309459 AK312375 BC010058 BC013050
    RefSeq transcript (Entrez)NM_000401 NM_001178083 NM_207122
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)EXT2
    Cluster EST : UnigeneHs.368404 [ NCBI ]
    CGAP (NCI)Hs.368404
    Alternative Splicing GalleryENSG00000151348
    Gene ExpressionEXT2 [ NCBI-GEO ]   EXT2 [ EBI - ARRAY_EXPRESS ]   EXT2 [ SEEK ]   EXT2 [ MEM ]
    Gene Expression Viewer (FireBrowse)EXT2 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)2132
    GTEX Portal (Tissue expression)EXT2
    Human Protein AtlasENSG00000151348-EXT2 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ93063   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ93063  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ93063
    Splice isoforms : SwissVarQ93063
    Catalytic activity : Enzyme2.4.1.224|2.4.1.225 [ Enzyme-Expasy ]   2.4.1.224|2.4.1.2252.4.1.224|2.4.1.225 [ IntEnz-EBI ]   2.4.1.224|2.4.1.225 [ BRENDA ]   2.4.1.224|2.4.1.225 [ KEGG ]   
    PhosPhoSitePlusQ93063
    Domains : Interpro (EBI)Exostosin    Exostosin-2    EXT_C    Nucleotide-diphossugar_trans   
    Domain families : Pfam (Sanger)Exostosin (PF03016)    Glyco_transf_64 (PF09258)   
    Domain families : Pfam (NCBI)pfam03016    pfam09258   
    Conserved Domain (NCBI)EXT2
    DMDM Disease mutations2132
    Blocks (Seattle)EXT2
    SuperfamilyQ93063
    Human Protein Atlas [tissue]ENSG00000151348-EXT2 [tissue]
    Peptide AtlasQ93063
    HPRD00599
    IPIIPI00004047   IPI00922132   IPI00942173   IPI00976549   IPI00953659   
    Protein Interaction databases
    DIP (DOE-UCLA)Q93063
    IntAct (EBI)Q93063
    FunCoupENSG00000151348
    BioGRIDEXT2
    STRING (EMBL)EXT2
    ZODIACEXT2
    Ontologies - Pathways
    QuickGOQ93063
    Ontology : AmiGOGolgi membrane  ossification  mesoderm formation  protein binding  endoplasmic reticulum  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  Golgi apparatus  Golgi apparatus  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  acetylglucosaminyltransferase activity  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  membrane  integral component of membrane  transferase activity, transferring glycosyl groups  transferase activity, transferring glycosyl groups  cell differentiation  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  UDP-N-acetylglucosamine transferase complex  metal ion binding  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  extracellular exosome  
    Ontology : EGO-EBIGolgi membrane  ossification  mesoderm formation  protein binding  endoplasmic reticulum  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  Golgi apparatus  Golgi apparatus  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  acetylglucosaminyltransferase activity  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  membrane  integral component of membrane  transferase activity, transferring glycosyl groups  transferase activity, transferring glycosyl groups  cell differentiation  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  UDP-N-acetylglucosamine transferase complex  metal ion binding  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  extracellular exosome  
    Pathways : KEGGGlycosaminoglycan biosynthesis - heparan sulfate / heparin   
    REACTOMEQ93063 [protein]
    REACTOME PathwaysR-HSA-3656253 [pathway]   
    NDEx NetworkEXT2
    Atlas of Cancer Signalling NetworkEXT2
    Wikipedia pathwaysEXT2
    Orthology - Evolution
    OrthoDB2132
    GeneTree (enSembl)ENSG00000151348
    Phylogenetic Trees/Animal Genes : TreeFamEXT2
    HOGENOMQ93063
    Homologs : HomoloGeneEXT2
    Homology/Alignments : Family Browser (UCSC)EXT2
    Gene fusions - Rearrangements
    Fusion : MitelmanACCS/EXT2 [11p11.2/11p11.2]  [t(11;11)(p11;p11)]  
    Fusion : MitelmanEXT2/ALKBH3 [11p11.2/11p11.2]  [t(11;11)(p11;p11)]  
    Fusion : MitelmanEXT2/ALX4 [11p11.2/11p11.2]  [t(11;11)(p11;p11)]  
    Fusion PortalEXT2 11p11.2 ALKBH3 11p11.2 SKCM
    Fusion PortalEXT2 11p11.2 ALX4 11p11.2 BRCA
    Fusion : FusionGDB11405    12333    12334    12335    12336    24662    32698    6186    8701   
    Fusion : Fusion_HubABI3BP--EXT2    ACCS--EXT2    CD44--EXT2    CSTB--EXT2    DDX10--EXT2    DGCR2--EXT2    EXT2--ALKBH3    EXT2--ALX4    EXT2--C11ORF73    EXT2--C14ORF80    EXT2--CCDC15    EXT2--EXT1    EXT2--IER3    EXT2--LRRC4C    EXT2--MICAL2   
    EXT2--MIR670HG    EXT2--NDUFC2    EXT2--PAPOLA    EXT2--PARVA    EXT2--PHF21A    EXT2--PPIC    EXT2--PRMT10    EXT2--PSPC1    EXT2--RNF214    EXT2--TTC17    EXT2--USP7    EXT2--UVRAG    EXT2--ZNF704    FDFT1--EXT2    NAALADL2--EXT2   
    ODZ4--EXT2    PRKRIR--EXT2    PTPRG--EXT2    SAMD4A--EXT2    SBF2--EXT2    SERGEF--EXT2    ZXDC--EXT2   
    Fusion : QuiverEXT2
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerEXT2 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)EXT2
    dbVarEXT2
    ClinVarEXT2
    1000_GenomesEXT2 
    Exome Variant ServerEXT2
    ExAC (Exome Aggregation Consortium)ENSG00000151348
    GNOMAD BrowserENSG00000151348
    Varsome BrowserEXT2
    Genetic variants : HAPMAP2132
    Genomic Variants (DGV)EXT2 [DGVbeta]
    DECIPHEREXT2 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisEXT2 
    Mutations
    ICGC Data PortalEXT2 
    TCGA Data PortalEXT2 
    Broad Tumor PortalEXT2
    OASIS PortalEXT2 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICEXT2  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DEXT2
    Mutations and Diseases : HGMDEXT2
    LOVD (Leiden Open Variation Database)Multiple Osteochondroma Mutation Database
    BioMutasearch EXT2
    DgiDB (Drug Gene Interaction Database)EXT2
    DoCM (Curated mutations)EXT2 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)EXT2 (select a term)
    intoGenEXT2
    NCG5 (London)EXT2
    Cancer3DEXT2(select the gene name)
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM133701    608210    616682   
    Orphanet3247    10684   
    DisGeNETEXT2
    MedgenEXT2
    Genetic Testing Registry EXT2
    NextProtQ93063 [Medical]
    TSGene2132
    GENETestsEXT2
    Target ValidationEXT2
    Huge Navigator EXT2 [HugePedia]
    snp3D : Map Gene to Disease2132
    BioCentury BCIQEXT2
    ClinGenEXT2 (curated)
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD2132
    Chemical/Pharm GKB GenePA27925
    Clinical trialEXT2
    Miscellaneous
    canSAR (ICR)EXT2 (select the gene name)
    DataMed IndexEXT2
    Probes
    Litterature
    PubMed113 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineEXT2
    EVEXEXT2
    GoPubMedEXT2
    iHOPEXT2
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Mon Aug 26 18:54:41 CEST 2019

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