The CHST3 gene provides instructions for making an enzyme called chondroitin 6-O-sulfotransferase 1 or C6ST-1. This enzyme has an important role in the development and maintenance of the skeleton. In particular, it is essential for the normal development of cartilage, which is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.

The C6ST-1 enzyme modifies molecules called chondroitin sulfate proteoglycans, which are abundant in cartilage and give this tissue its rubbery, gel-like consistency. The C6ST-1 enzyme carries out a process known as sulfation, in which a chemical group called a sulfate is transferred from one chemical compound to another. Specifically, the enzyme takes sulfate from a molecule called 3'-phosphoadenyl-5'-phosphosulfate (PAPS) and adds it to a specific location on chondroitin sulfate proteoglycans. Sulfation of these molecules is a critical step in cartilage formation.

Tests Listed in the Genetic Testing Registry

• Tests of CHST3

Scientific Articles on PubMed

• PubMed

Catalog of Genes and Diseases from OMIM

• CARBOHYDRATE SULFOTRANSFERASE 3; CHST3

Gene and Variant Databases

• NCBI Gene
• ClinVar

• Hermanns P, Unger S, Rossi A, Perez-Aytes A, Cortina H, Bonafe L, Boccone L, Setzu V, Dutoit M, Sangiorgi L, Pecora F, Reicherter K, Nishimura G, Spranger J, Zabel B, Superti-Furga A. Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis. Am J Hum Genet. 2008 Jun;82(6):1368-74. doi: 10.1016/j.ajhg.2008.05.006. Citation on PubMed or Free article on PubMed Central
• Thiele H, Sakano M, Kitagawa H, Sugahara K, Rajab A, Hohne W, Ritter H, Leschik G, Nurnberg P, Mundlos S. Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10155-60. doi: 10.1073/pnas.0400334101. Epub 2004 Jun 23. Citation on PubMed or Free article on PubMed Central
• Tsutsumi K, Shimakawa H, Kitagawa H, Sugahara K. Functional expression and genomic structure of human chondroitin 6-sulfotransferase. FEBS Lett. 1998 Dec 18;441(2):235-41. doi: 10.1016/s0014-5793(98)01532-4. Citation on PubMed
• Tuysuz B, Mizumoto S, Sugahara K, Celebi A, Mundlos S, Turkmen S. Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3. Clin Genet. 2009 Apr;75(4):375-83. doi: 10.1111/j.1399-0004.2009.01167.x. Citation on PubMed
• Unger S, Lausch E, Rossi A, Megarbane A, Sillence D, Alcausin M, Aytes A, Mendoza-Londono R, Nampoothiri S, Afroze B, Hall B, Lo IF, Lam ST, Hoefele J, Rost I, Wakeling E, Mangold E, Godbole K, Vatanavicharn N, Franco LM, Chandler K, Hollander S, Velten T, Reicherter K, Spranger J, Robertson S, Bonafe L, Zabel B, Superti-Furga A. Phenotypic features of carbohydrate sulfotransferase 3 (CHST3) deficiency in 24 patients: congenital dislocations and vertebral changes as principal diagnostic features. Am J Med Genet A. 2010 Oct;152A(10):2543-9. doi: 10.1002/ajmg.a.33641. Citation on PubMed
• van Roij MH, Mizumoto S, Yamada S, Morgan T, Tan-Sindhunata MB, Meijers-Heijboer H, Verbeke JI, Markie D, Sugahara K, Robertson SP. Spondyloepiphyseal dysplasia, Omani type: further definition of the phenotype. Am J Med Genet A. 2008 Sep 15;146A(18):2376-84. doi: 10.1002/ajmg.a.32482. Citation on PubMed