EXT1 gene

exostosin glycosyltransferase 1

The EXT1 gene provides instructions for producing a protein called exostosin-1. This protein is found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, exostosin-1 attaches (binds) to another protein, exostosin-2, to form a complex that modifies heparan sulfate. Heparan sulfate is a complex of sugar molecules (a polysaccharide) that is added to proteins to form proteoglycans, which are proteins attached to several sugars. Heparan sulfate is involved in regulating a variety of body processes including blood clotting and the formation of blood vessels (angiogenesis). It also has a role in the spreading (metastasis) of cancer cells.

About 480 mutations in the EXT1 gene have been identified in people with hereditary multiple osteochondromas type 1, a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. Most of these mutations are known as "loss-of-function" mutations because they prevent any functional exostosin-1 protein from being made. The loss of functional exostosin-1 protein prevents it from forming a complex with the exostosin-2 protein and adding heparan sulfate to proteins. It is unclear how this impairment leads to the signs and symptoms of hereditary multiple osteochondromas.

The EXT1 gene is located in a region of chromosome 8 that is deleted in people with trichorhinophalangeal syndrome type II (TRPS II). TRPS II is a condition that causes bone and joint malformations including multiple osteochondromas (described above); distinctive facial features; intellectual disability; and abnormalities of the skin, hair, teeth, sweat glands, and nails. As a result of this deletion, affected individuals are missing one copy of the EXT1 gene in each cell. A shortage of exostosin-1 protein causes the osteochondromas in people with TRPS II. The deletion of other genes near the EXT1 gene likely contributes to the additional features of this condition.

Cytogenetic Location: 8q24.11, which is the long (q) arm of chromosome 8 at position 24.11

Molecular Location: base pairs 117,794,490 to 118,111,826 on chromosome 8 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 8q24.11, which is the long (q) arm of chromosome 8 at position 24.11
  • exostoses (multiple) 1
  • exostosin 1
  • EXT
  • Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase
  • N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase