EXT2 exostoses (multiple) 2

2002-03-01 Judith VMG Bovée Affiliation

Identity

HGNC

EXT2

LOCATION

11p11.2

IMAGE

LEGEND

EXT2 (11p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LOCUSID

2132

ALIAS

SOTV,SSMS

FUSION GENES

Show Gene Fusions

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

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

Bibliography

Pubmed ID	Last Year	Title	Authors
10441575	1999	EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.	Bovée JV et al
9576285	1998	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 et al
9110175	1997	The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans.	Clines GA et al
8317501	1993	Genetic heterogeneity in families with hereditary multiple exostoses.	Cook A et al
7726168	1995	Hereditary 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
10318803	1999	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 et al
9756849	1998	The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.	Lind T et al
10529789	1999	New perspectives on the molecular basis of hereditary bone tumours.	McCormick C et al
7726169	1995	Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.	Raskind WH et al
10545594	1999	A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses.	Simmons AD et al
10878610	2000	EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.	Stickens D et al
8162019	1994	Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11.	Wu YQ et al
7668264	1995	Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11.	Wuyts W et al
10679937	2000	Molecular 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 ID	Transcript ID	Uniprot
ENSG00000151348	ENST00000343631	Q93063
ENSG00000151348	ENST00000358681	Q93063
ENSG00000151348	ENST00000395673	Q93063
ENSG00000151348	ENST00000527014	E9PNL9
ENSG00000151348	ENST00000532479	E9PJA5
ENSG00000151348	ENST00000533608	Q93063

Expression (GTEx)

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

Pathway	Source	External ID
Glycosaminoglycan biosynthesis - heparan sulfate / heparin	KEGG	ko00534
Glycosaminoglycan biosynthesis - heparan sulfate / heparin	KEGG	hsa00534
Metabolic pathways	KEGG	hsa01100
Glycosaminoglycan biosynthesis, heparan sulfate backbone	KEGG	hsa_M00059
Glycosaminoglycan biosynthesis, heparan sulfate backbone	KEGG	M00059
Metabolism	REACTOME	R-HSA-1430728
Metabolism of carbohydrates	REACTOME	R-HSA-71387
Glycosaminoglycan metabolism	REACTOME	R-HSA-1630316
Heparan sulfate/heparin (HS-GAG) metabolism	REACTOME	R-HSA-1638091
HS-GAG biosynthesis	REACTOME	R-HSA-2022928

References

Pubmed ID	Year	Title	Citations
17293876	2007	A genome-wide association study identifies novel risk loci for type 2 diabetes.	990
19380854	2009	Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry.	108
18633108	2008	Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.	86
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
17761672	2007	Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation.	65
17928989	2007	Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population.	63
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
17786204	2007	Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function.	56
19008344	2009	Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians.	50
19008344	2009	Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians.	50

Citation

Judith VMG Bovée

EXT2 exostoses (multiple) 2

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/213/ext2

Historical Card

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

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