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EXT1 (exostosin 1)

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

Other namesEXT
LGCR
LGS
TRPS2
TTV
HGNC (Hugo) EXT1
LocusID (NCBI) 2131
Atlas_Id 212
Location 8q24.11
Location_base_pair Starts at 118811602 and ends at 119124058 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
ADGRB1 (8q24.3) / EXT1 (8q24.11)DSCAM (21q22.2) / EXT1 (8q24.11)EEF1A1 (6q13) / EXT1 (8q24.11)
EXT1 (8q24.11) / CLUL1 (18p11.32)EXT1 (8q24.11) / DCTN6 (8p12)EXT1 (8q24.11) / EXT1 (8q24.11)
EXT1 (8q24.11) / FAM155A (13q33.3)EXT1 (8q24.11) / FAM177A1 (14q13.2)EXT1 (8q24.11) / OC90 (8q24.22)
EXT1 (8q24.11) / RSF1 (11q14.1)EXT1 (8q24.11) / SAMD12 (8q24.12)EXT1 (8q24.11) / WDYHV1 (8q24.13)
LRRC6 (8q24.22) / EXT1 (8q24.11)RAB28 (4p15.33) / EXT1 (8q24.11)RAD21 (8q24.11) / EXT1 (8q24.11)

DNA/RNA

 
Description 11 exons, spans approximately 350 kb of genomic DNA
Transcription 3.4 kb

Protein

Description 746 amino acids, 86.304 kDa
Expression mRNA is ubiquitously expressed (also in chondrocytes), highest level of expression in liver.
Localisation endoplasmic reticulum
Function a tumour suppressor function is suggested; EXT1 is an endoplasmic reticulum (ER) resident type II transmembrane glycoprotein whose expression in cells alters the synthesis and display of cell surface heparan sulfate, and EXT1 was suggested to be involved in chain polymerization of heparan sulphate; an EXT1 homologue in Drosophila melanogaster (tout-velu, Ttv) was demonstrated to be involved in heparan sulphate proteoglycan biosynthesis controlling diffusion of an important segment polarity protein called Hedgehog (Hh)
Homology human EXT2, EXTL1, EXTL2 and EXTL3, mouse Ext1, Drosophila tout velu

Mutations

Germinal germline mutations in EXT1 are causative for hereditary multiple exostoses, a genetically heterogeneous autosomal dominant disorder; mutations include nucleotide substitutions (54%), small deletions (27%) and small insertions (16%), 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 1-5% of the HME cases
Cytogenetics clonal aberrations were found at band 8q24.1 in sporadic and hereditary osteochondromas using cytogenetic analysis; loss of heterozygosity was almost exclusively found at the EXT1 locus in 5 out of 14 osteochondromas
Oncogenesis two patients with multiple osteochondromas demonstrated a germline mutation combined with loss of the remaining wild type allele in three osteochondromas, supporting the Knudson's two hit model for tumour suppressor genes in osteochondroma development; these results indicate that in cartilaginous cells of the growth plate inactivation of both copies of the EXT1-gene is required for osteochondroma formation in hereditary cases
  

Bibliography

Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1).
Ahn J, Lüdecke HJ, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE
Nature genetics. 1995 ; 11 (2) : 137-143.
PMID 7550340
 
Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion.
Bellaiche Y, The I, Perrimon N
Nature. 1998 ; 394 (6688) : 85-88.
PMID 9665133
 
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
 
Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma.
Bovée JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ, Hogendoorn PC
Genes, chromosomes & cancer. 1999 ; 26 (3) : 237-246.
PMID 10502322
 
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
 
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
 
Expression and functional analysis of mouse EXT1, a homolog of the human multiple exostoses type 1 gene.
Lin X, Gan L, Klein WH, Wells D
Biochemical and biophysical research communications. 1998 ; 248 (3) : 738-743.
PMID 9703997
 
Isolation of the mouse cDNA homologous to the human EXT1 gene responsible for Hereditary Multiple Exostoses.
Lin X, Wells D
DNA sequence : the journal of DNA sequencing and mapping. 1997 ; 7 (3-4) : 199-202.
PMID 9254013
 
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
 
The murine Ext1 gene shows a high level of sequence similarity with its human homologue and is part of a conserved linkage group on chromosome 15.
Lohmann DR, Buiting K, Lüdecke HJ, Horsthemke B
Cytogenetics and cell genetics. 1997 ; 76 (3-4) : 164-166.
PMID 9186511
 
Genomic organization and promoter structure of the human EXT1 gene.
Lüdecke HJ, Ahn J, Lin X, Hill A, Wagner MJ, Schomburg L, Horsthemke B, Wells DE
Genomics. 1997 ; 40 (2) : 351-354.
PMID 9119404
 
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
 
The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate.
McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F
Nature genetics. 1998 ; 19 (2) : 158-161.
PMID 9620772
 
Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses.
Mertens F, Rydholm A, Kreicbergs A, Willén H, Jonsson K, Heim S, Mitelman F, Mandahl N
Genes, chromosomes & cancer. 1994 ; 9 (1) : 8-12.
PMID 7507706
 
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
 
Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan.
The I, Bellaiche Y, Perrimon N
Molecular cell. 1999 ; 4 (4) : 633-639.
PMID 10549295
 

Citation

This paper should be referenced as such :
Boée, JVMG
EXT1 (exostoses (multiple) 1)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):184-185.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/EXT1ID212.html
History of this paper:
Bovée, JVMG. EXT1 (exostoses (multiple) 1). Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):3-4.
http://documents.irevues.inist.fr/bitstream/handle/2042/37575/01-2000-EXT1ID212.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Bone tumors: an overview
Bone: Chondrosarcoma
Bone: Osteochondroma

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

External links

Nomenclature
HGNC (Hugo)EXT1   3512
Cards
AtlasEXT1ID212
Entrez_Gene (NCBI)EXT1  2131  exostosin glycosyltransferase 1
GeneCards (Weizmann)EXT1
Ensembl hg19 (Hinxton)ENSG00000182197 [Gene_View]  chr8:118811602-119124058 [Contig_View]  EXT1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000182197 [Gene_View]  chr8:118811602-119124058 [Contig_View]  EXT1 [Vega]
ICGC DataPortalENSG00000182197
TCGA cBioPortalEXT1
AceView (NCBI)EXT1
Genatlas (Paris)EXT1
WikiGenes2131
SOURCE (Princeton)EXT1
Genomic and cartography
GoldenPath hg19 (UCSC)EXT1  -     chr8:118811602-119124058 -  8q24.11   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)EXT1  -     8q24.11   [Description]    (hg38-Dec_2013)
EnsemblEXT1 - 8q24.11 [CytoView hg19]  EXT1 - 8q24.11 [CytoView hg38]
Mapping of homologs : NCBIEXT1 [Mapview hg19]  EXT1 [Mapview hg38]
OMIM133700   215300   608177   
Gene and transcription
Genbank (Entrez)AK130054 AK313129 BC001174 DQ891868 DQ895056
RefSeq transcript (Entrez)NM_000127
RefSeq genomic (Entrez)NC_000008 NC_018919 NG_007455 NT_008046 NW_004929340
Consensus coding sequences : CCDS (NCBI)EXT1
Cluster EST : UnigeneHs.492618 [ NCBI ]
CGAP (NCI)Hs.492618
Alternative Splicing GalleryENSG00000182197
Gene ExpressionEXT1 [ NCBI-GEO ]   EXT1 [ EBI - ARRAY_EXPRESS ]   EXT1 [ SEEK ]   EXT1 [ MEM ]
Gene Expression Viewer (FireBrowse)EXT1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2131
GTEX Portal (Tissue expression)EXT1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16394 (Uniprot)
NextProtQ16394  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ16394
Splice isoforms : SwissVarQ16394 (Swissvar)
Catalytic activity : Enzyme2.4.1.224 [ Enzyme-Expasy ]   2.4.1.2242.4.1.224 [ IntEnz-EBI ]   2.4.1.224 [ BRENDA ]   2.4.1.224 [ KEGG ]   
PhosPhoSitePlusQ16394
Domains : Interpro (EBI)Exostosin    Exostosin-1    EXT_C    Nucleotide-diphossugar_trans   
Domain families : Pfam (Sanger)Exostosin (PF03016)    Glyco_transf_64 (PF09258)   
Domain families : Pfam (NCBI)pfam03016    pfam09258   
DMDM Disease mutations2131
Blocks (Seattle)EXT1
SuperfamilyQ16394
Human Protein AtlasENSG00000182197
Peptide AtlasQ16394
HPRD00598
IPIIPI00293128   IPI00893515   IPI00893384   
Protein Interaction databases
DIP (DOE-UCLA)Q16394
IntAct (EBI)Q16394
FunCoupENSG00000182197
BioGRIDEXT1
STRING (EMBL)EXT1
ZODIACEXT1
Ontologies - Pathways
QuickGOQ16394
Ontology : AmiGOGolgi membrane  skeletal system development  ossification  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  gastrulation  axon guidance  endoderm development  mesoderm development  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  integral component of membrane  transferase activity, transferring glycosyl groups  olfactory bulb development  integral component of endoplasmic reticulum membrane  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  metal ion binding  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  embryonic skeletal joint development  
Ontology : EGO-EBIGolgi membrane  skeletal system development  ossification  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  gastrulation  axon guidance  endoderm development  mesoderm development  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  integral component of membrane  transferase activity, transferring glycosyl groups  olfactory bulb development  integral component of endoplasmic reticulum membrane  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  metal ion binding  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  embryonic skeletal joint development  
Pathways : KEGGGlycosaminoglycan biosynthesis - heparan sulfate / heparin   
REACTOMEQ16394 [protein]
REACTOME PathwaysR-HSA-3656253 Defective EXT1 causes exostoses 1, TRPS2 and CHDS [pathway]
REACTOME PathwaysR-HSA-2022928 HS-GAG biosynthesis [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkEXT1
Wikipedia pathwaysEXT1
Orthology - Evolution
OrthoDB2131
GeneTree (enSembl)ENSG00000182197
Phylogenetic Trees/Animal Genes : TreeFamEXT1
Homologs : HomoloGeneEXT1
Homology/Alignments : Family Browser (UCSC)EXT1
Gene fusions - Rearrangements
Fusion : MitelmanADGRB1/EXT1 [8q24.3/8q24.11]  [t(8;8)(q24;q24)]  
Fusion : MitelmanEXT1/FAM155A [8q24.11/13q33.3]  [t(8;13)(q24;q33)]  
Fusion : MitelmanEXT1/OC90 [8q24.11/8q24.22]  [t(8;8)(q24;q24)]  
Fusion : MitelmanEXT1/RSF1 [8q24.11/11q14.1]  [t(8;11)(q24;q14)]  
Fusion : MitelmanEXT1/SAMD12 [8q24.11/8q24.12]  [t(8;8)(q24;q24)]  
Fusion : MitelmanEXT1/WDYHV1 [8q24.11/8q24.13]  [t(8;8)(q24;q24)]  
Fusion : MitelmanLRRC6/EXT1 [8q24.22/8q24.11]  [t(8;8)(q24;q24)]  
Fusion: TCGABAI1 EXT1 8q24.11 LGG
Fusion: TCGAEXT1 8q24.11 FAM155A 13q33.3 BLCA
Fusion: TCGAEXT1 8q24.11 OC90 8q24.22 LUAD
Fusion: TCGAEXT1 8q24.11 RSF1 11q14.1 BRCA
Fusion: TCGAEXT1 8q24.11 SAMD12 8q24.12 BRCA HNSC
Fusion: TCGAEXT1 8q24.11 WDYHV1 8q24.13 BLCA
Fusion: TCGALRRC6 8q24.22 EXT1 8q24.11 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerEXT1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EXT1
dbVarEXT1
ClinVarEXT1
1000_GenomesEXT1 
Exome Variant ServerEXT1
ExAC (Exome Aggregation Consortium)EXT1 (select the gene name)
Genetic variants : HAPMAP2131
Genomic Variants (DGV)EXT1 [DGVbeta]
Mutations
ICGC Data PortalEXT1 
TCGA Data PortalEXT1 
Broad Tumor PortalEXT1
OASIS PortalEXT1 [ Somatic mutations - Copy number]
Cancer Gene: CensusEXT1 
Somatic Mutations in Cancer : COSMICEXT1 
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)Multiple Osteochondroma Mutation Database
BioMutasearch EXT1
DgiDB (Drug Gene Interaction Database)EXT1
DoCM (Curated mutations)EXT1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)EXT1 (select a term)
intoGenEXT1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)8:118811602-119124058  ENSG00000182197
CONAN: Copy Number AnalysisEXT1 
Mutations and Diseases : HGMDEXT1
OMIM133700    215300    608177   
MedgenEXT1
Genetic Testing Registry EXT1
NextProtQ16394 [Medical]
TSGene2131
GENETestsEXT1
Huge Navigator EXT1 [HugePedia]
snp3D : Map Gene to Disease2131
BioCentury BCIQEXT1
ClinGenEXT1 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2131
Chemical/Pharm GKB GenePA27924
Clinical trialEXT1
Miscellaneous
canSAR (ICR)EXT1 (select the gene name)
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed88 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineEXT1
EVEXEXT1
GoPubMedEXT1
iHOPEXT1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu May 26 11:40:23 CEST 2016

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