EXT2 exostoses (multiple) 2

2002-03-01   Judith VMG Bovée  

Identity

HGNC
EXT2
LOCATION
11p11.2
IMAGE
Atlas Image
LEGEND
EXT2 (11p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
2132
ALIAS
SOTV,SSMS
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image

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

Proteins

Description

718 amino acids; 82.2 kDa

Expression

mRNA is ubiquitously expressed. In mouse embryos, 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

    Entity name
    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

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    104415751999EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.Bovée JV et al
    95762851998Clonal 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 et al
    91101751997The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans.Clines GA et al
    83175011993Genetic heterogeneity in families with hereditary multiple exostoses.Cook A et al
    77261681995Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8.Hecht JT et al
    103188031999The 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 et al
    97568491998The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.Lind T et al
    105297891999New perspectives on the molecular basis of hereditary bone tumours.McCormick C et al
    77261691995Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.Raskind WH et al
    105455941999A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses.Simmons AD et al
    108786102000EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.Stickens D et al
    81620191994Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11.Wu YQ et al
    76682641995Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11.Wuyts W et al
    106799372000Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.Wuyts W et al

    Other Information

    Locus ID:

    NCBI: 2132
    MIM: 608210
    HGNC: 3513
    Ensembl: ENSG00000151348

    Variants:

    dbSNP: 2132
    ClinVar: 2132
    TCGA: ENSG00000151348
    COSMIC: EXT2

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000151348ENST00000343631Q93063
    ENSG00000151348ENST00000358681Q93063
    ENSG00000151348ENST00000395673Q93063
    ENSG00000151348ENST00000527014E9PNL9
    ENSG00000151348ENST00000532479E9PJA5
    ENSG00000151348ENST00000533608Q93063

    Expression (GTEx)

    0
    50
    100
    150
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Glycosaminoglycan biosynthesis - heparan sulfate / heparinKEGGko00534
    Glycosaminoglycan biosynthesis - heparan sulfate / heparinKEGGhsa00534
    Metabolic pathwaysKEGGhsa01100
    Glycosaminoglycan biosynthesis, heparan sulfate backboneKEGGhsa_M00059
    Glycosaminoglycan biosynthesis, heparan sulfate backboneKEGGM00059
    MetabolismREACTOMER-HSA-1430728
    Metabolism of carbohydratesREACTOMER-HSA-71387
    Glycosaminoglycan metabolismREACTOMER-HSA-1630316
    Heparan sulfate/heparin (HS-GAG) metabolismREACTOMER-HSA-1638091
    HS-GAG biosynthesisREACTOMER-HSA-2022928

    References

    Pubmed IDYearTitleCitations
    381550092024EXT2: a novel prognostic and predictive biomarker for head and neck squamous cell carcinoma.0
    381550092024EXT2: a novel prognostic and predictive biomarker for head and neck squamous cell carcinoma.0
    367691582023Insights into the Peritumoural Brain Zone of Glioblastoma: CDK4 and EXT2 May Be Potential Drivers of Malignancy.4
    367691582023Insights into the Peritumoural Brain Zone of Glioblastoma: CDK4 and EXT2 May Be Potential Drivers of Malignancy.4
    351941252022Prevalence of neural epidermal growth factor-like 1- and exostosin 1/exostosin 2-associated membranous nephropathy: a single-center retrospective study in Japan.14
    352117662022Clinical survey of a pedigree with hereditary multiple exostoses and identification of EXT‑2 gene deletion mutation.0
    351941252022Prevalence of neural epidermal growth factor-like 1- and exostosin 1/exostosin 2-associated membranous nephropathy: a single-center retrospective study in Japan.14
    352117662022Clinical survey of a pedigree with hereditary multiple exostoses and identification of EXT‑2 gene deletion mutation.0
    334789712021In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes.34
    335961402021Identification of Novel Mutations in the EXT1 and EXT2 Genes of Chinese Patients with Hereditary Multiple Osteochondromas.0
    336322552021Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses.7
    342800072021A Novel Intronic Splicing Mutation in the EXT2 Gene of a Chinese Family with Multiple Osteochondroma.2
    343022132021Immunopathological analysis of the expression of glomerular exostosin 1 and exostosin 2 in Japanese patients with lupus nephritis.5
    344035212021Identification of a novel EXT2 frameshift mutation in a family with hereditary multiple exostoses by whole-exome sequencing.2
    334789712021In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes.34

    Citation

    Judith VMG Bovée

    EXT2 exostoses (multiple) 2

    Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

    Online version: http://atlasgeneticsoncology.org/gene/213/ext2-exostoses-(multiple)-2

    Historical Card

    2000-01-01 EXT2 exostoses (multiple) 2 by  Judith VMG Bovée 

    Afdeling Pathologie, Leids Universitair Medisch Centrum, Postbus 9600, L1-Q, 2300 RC Leiden, the Netherlands