EXT2 (gene)

Exostosin glycosyltransferase-2 is a protein that in humans is encoded by the EXT2 gene.^[5][6][7]

This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of Hereditary Multiple Exostoses (HME).^[7]

Gene location

The EXT2 gene is located on chromosome 11 in the human genome, its location is on the p arm of this chromosome.^[8] The p arm of a chromosome is the shorter arm of a chromosome.^[9]

Interactions

Included in the EXT family are EXT2,

Mutations that change the amino acid sequence of the exostosin glycosyltransferase-2 protein can lead to it becoming unfunctional. When this protein is unfunctional it causes the heparan sulfate chains to become shorter. The chains are still formed and extended by the other proteins encoded by the EXT family genes, although not to the same extent. This increases the likelihood that a cartilage cell will be placed incorrectly, as heparan sulfate is a bone and cartilage tumor suppressor. Since bone has a very specific structure, misplacing a cartilage cell in early growth is comparable to misplacement of a brick early on in construction of a wall. Misplacement in cartilage will result in cartilage tumor or tumors at the growth plates of long bones. This condition is known as hereditary multiple exostoses (HME) or hereditary multiple osteochondromas (HMO).[16] HME can also be the result of a mutation to the EXT1 gene or other EXT family genes.^[17] EXT1 mutations tend to be more severe with more exostoses and are the cause of 56-78% of human HME cases, except for in China where mutations of the EXT2 gene are more common. HME effects 1 in 50,000 people and is more commonly seen in males in a 1.5:1 ratio.^[18]

Heredity of the EXT2 Gene

EXT2 gene mutations are dominant

Further reading

• Wuyts W, Van Hul W (2000). "Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes". Human Mutation. 15 (3): 220–7.
  S2CID 45999816
  .
• Wuyts W, Ramlakhan S, Van Hul W, Hecht JT, van den Ouweland AM, Raskind WH, et al. (August 1995). "Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11". American Journal of Human Genetics. 57 (2): 382–7.
  PMID 7668264
  .
• Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, et al. (September 1996). "The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes". Nature Genetics. 14 (1): 25–32.
  S2CID 27148572
  .
• Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul EV, et al. (October 1996). "Positional cloning of a gene involved in hereditary multiple exostoses". Human Molecular Genetics. 5 (10): 1547–57.
  PMID 8894688
  .
• Clines GA, Ashley JA, Shah S, Lovett M (April 1997). "The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans". Genome Research. 7 (4): 359–67.
  PMID 9110175
  .
• Philippe C, Porter DE, Emerton ME, Wells DE, Simpson AH, Monaco AP (September 1997). "Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses". American Journal of Human Genetics. 61 (3): 520–8.
  PMID 9326317
  .
• Wuyts W, Van Hul W, De Boulle K, Hendrickx J, Bakker E, Vanhoenacker F, et al. (February 1998). "Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses". American Journal of Human Genetics. 62 (2): 346–54.
  PMID 9463333
  .
• McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F (June 1998). "The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate". Nature Genetics. 19 (2): 158–61.
  S2CID 25832441
  .
• Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K (October 1998). "The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate". The Journal of Biological Chemistry. 273 (41): 26265–8.
  PMID 9756849
  .
• Park KJ, Shin KH, Ku JL, Cho TJ, Lee SH, Choi IH, et al. (1999). "Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses". Journal of Human Genetics. 44 (4): 230–4.
  PMID 10429361
  .
• Xu L, Xia J, Jiang H, Zhou J, Li H, Wang D, et al. (1999). "Mutation analysis of hereditary multiple exostoses in the Chinese". Human Genetics. 105 (1–2): 45–50.
  PMID 10480354
  .
• Simmons AD, Musy MM, Lopes CS, Hwang LY, Yang YP, Lovett M (November 1999). "A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses". Human Molecular Genetics. 8 (12): 2155–64.
  PMID 10545594
  .
• McCormick C, Duncan G, Goutsos KT, Tufaro F (January 2000). "The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate". Proceedings of the National Academy of Sciences of the United States of America. 97 (2): 668–73.
  PMID 10639137
  .
• Kobayashi S, Morimoto K, Shimizu T, Takahashi M, Kurosawa H, Shirasawa T (February 2000). "Association of EXT1 and EXT2, hereditary multiple exostoses gene products, in Golgi apparatus". Biochemical and Biophysical Research Communications. 268 (3): 860–7.
  PMID 10679296
  .
• Shi YR, Wu JY, Tsai FJ, Lee CC, Tsai CH (April 2000). "An R223P mutation in EXT2 gene causes hereditary multiple exostoses". Human Mutation. 15 (4): 390–1.
  S2CID 83566600
  .
• Stickens D, Brown D, Evans GA (July 2000). "EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis". Developmental Dynamics. 218 (3): 452–64.
  S2CID 25986105
  .
• Bernard MA, Hall CE, Hogue DA, Cole WG, Scott A, Snuggs MB, et al. (February 2001). "Diminished levels of the putative tumor suppressor proteins EXT1 and EXT2 in exostosis chondrocytes". Cell Motility and the Cytoskeleton. 48 (2): 149–62.
  PMID 11169766
  .

External links

• Multiple Hereditary Exostoses Research Foundation

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