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Normal Function
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 binds to another protein, exostosin-2, to form a complex that modifies a protein called heparan sulfate.
Heparan sulfate is a complex of sugar molecules (a polysaccharide) that is added to proteins. Heparan sulfate helps regulate a variety of body processes, including cell signaling, cell interactions, and immune system functions. Heparan sulfate is also involved in regulating bone formation (ossification) and the growth and specialization (differentiation) of cartilage-forming cells called chondrocytes. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development.
Health Conditions Related to Genetic Changes
Hereditary multiple osteochondromas
Genetic changes that cause disease are called pathogenic variants. Hundreds of pathogenic variants in the EXT1 gene can cause hereditary multiple osteochondromas, a condition in which people develop multiple noncancerous (benign) bone tumors called osteochondromas. EXT1 gene variants cause a form of the condition called hereditary multiple osteochondromas type 1.
Most of the pathogenic variants in the EXT1 gene that cause hereditary multiple osteochondromas are known as "loss-of-function variants" because they prevent any functional exostosin-1 protein from being made. Without functional exostosin-1 to form a complex with exostosin-2, heparan sulfate is not properly modified. This likely disrupts ossification and chondrocyte differentiation, resulting in the formation of the bone tumors seen in people with hereditary multiple osteochondromas.
More About This Health ConditionTrichorhinophalangeal syndrome type II
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; distinctive facial features; intellectual disabilities; 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 proteins causes osteochondromas in people with TRPS II. The deletion of additional genes near the EXT1 gene likely contributes to the other features of this condition.
More About This Health ConditionOther Names for This Gene
- exostosin 1
- EXT
- EXT1_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Francannet C, Cohen-Tanugi A, Le Merrer M, Munnich A, Bonaventure J, Legeai-Mallet L. Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet. 2001 Jul;38(7):430-4. doi: 10.1136/jmg.38.7.430. Citation on PubMed or Free article on PubMed Central
- Lonie L, Porter DE, Fraser M, Cole T, Wise C, Yates L, Wakeling E, Blair E, Morava E, Monaco AP, Ragoussis J. Determination of the mutation spectrum of the EXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas, and exclusion of six candidate genes in EXT negative cases. Hum Mutat. 2006 Nov;27(11):1160. doi: 10.1002/humu.9467. Citation on PubMed
- Maas SM, Shaw AC, Bikker H, Ludecke HJ, van der Tuin K, Badura-Stronka M, Belligni E, Biamino E, Bonati MT, Carvalho DR, Cobben J, de Man SA, Den Hollander NS, Di Donato N, Garavelli L, Gronborg S, Herkert JC, Hoogeboom AJ, Jamsheer A, Latos-Bielenska A, Maat-Kievit A, Magnani C, Marcelis C, Mathijssen IB, Nielsen M, Otten E, Ousager LB, Pilch J, Plomp A, Poke G, Poluha A, Posmyk R, Rieubland C, Silengo M, Simon M, Steichen E, Stumpel C, Szakszon K, Polonkai E, van den Ende J, van der Steen A, van Essen T, van Haeringen A, van Hagen JM, Verheij JB, Mannens MM, Hennekam RC. Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome. Eur J Med Genet. 2015 May;58(5):279-92. doi: 10.1016/j.ejmg.2015.03.002. Epub 2015 Mar 16. Citation on PubMed
- McCormick C, Duncan G, Goutsos KT, Tufaro F. The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):668-73. doi: 10.1073/pnas.97.2.668. Citation on PubMed or Free article on PubMed Central
- Sefcik R, Earl D. Hereditary Multiple Osteochondromas. 2000 Aug 3 [updated 2026 Jan 29]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1235/ Citation on PubMed
- Tuysuz B, Gunes N, Alkaya DU. Trichorhinophalangeal Syndrome. 2017 Apr 20 [updated 2024 Mar 21]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK425926/ Citation on PubMed
- Wuyts W, Van Hul W, De Boulle K, Hendrickx J, Bakker E, Vanhoenacker F, Mollica F, Ludecke HJ, Sayli BS, Pazzaglia UE, Mortier G, Hamel B, Conrad EU, Matsushita M, Raskind WH, Willems PJ. Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses. Am J Hum Genet. 1998 Feb;62(2):346-54. doi: 10.1086/301726. Citation on PubMed or Free article on PubMed Central
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