Normal Function
The SOX10 gene belongs to a family of genes that plays a critical role in the formation of tissues and organs during embryonic development. The SOX gene family also maintains the normal function of certain cells after birth. To carry out these roles, proteins made by genes in the SOX family bind to specific areas of DNA. By attaching to critical regions near genes, SOX proteins help control the activity of those genes. SOX proteins are called transcription factors on the basis of this action.
During embryonic development, the SOX10 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo, where they give rise to many different types of cells. The protein made by the SOX10 gene directs the activity of other genes (such as MITF) that signal neural crest cells to become more specific cell types. In particular, the SOX10 protein is essential for the formation of nerves in the intestine (enteric nerves) and for the production of specialized cells called melanocytes. Melanocytes produce melanin, a pigment that contributes to skin, hair, and eye color. Melanin is also involved in the normal function of the inner ear.
Health Conditions Related to Genetic Changes
Waardenburg syndrome
Variants (also known as mutations) in the SOX10 gene have been identified in people with Waardenburg syndrome type II and type IV (also known as Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome). Both types of Waardenburg syndrome are characterized by changes in skin, hair, and eye coloring and hearing loss. People with type IV also have an intestinal disorder called Hirschsprung disease that causes severe constipation or intestinal blockage.
Most SOX10 gene variants lead to the production of an abnormal version of the SOX10 protein or prevent the gene from making any protein. An abnormal or missing SOX10 protein cannot control genes that signal neural crest cells to become specific cell types. As a result, enteric nerves and melanocytes do not form normally during embryonic development. Missing enteric nerves in certain parts of the intestine cause the signs and symptoms of Hirschsprung disease. A lack of melanocytes affects the coloring of skin, hair, and eyes and causes the hearing loss characteristic of Waardenburg syndrome.
Researchers have found that variants in the SOX10 gene also cause a similar disorder known as peripheral demyelinating neuropathy, central demyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH). This rare condition is a variant of Waardenburg syndrome type IV that also affects other parts of the nervous system. Like variants that cause other types of Waardenburg syndrome, the variants involved in PCWH lead to the production of an abnormal version of the SOX10 protein that is unable to direct the activity of other genes.
More About This Health ConditionHirschsprung disease
MedlinePlus Genetics provides information about Hirschsprung disease
More About This Health ConditionKallmann syndrome
MedlinePlus Genetics provides information about Kallmann syndrome
More About This Health ConditionOther Names for This Gene
- DOM
- dominant megacolon, mouse, human homolog of
- SOX10_HUMAN
- SRY (sex determining region Y)-box 10
- SRY box 10
- SRY-related HMG-box gene 10
- transcription factor SOX-10
- WS4
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bondurand N, Dastot-Le Moal F, Stanchina L, Collot N, Baral V, Marlin S, Attie-Bitach T, Giurgea I, Skopinski L, Reardon W, Toutain A, Sarda P, Echaieb A, Lackmy-Port-Lis M, Touraine R, Amiel J, Goossens M, Pingault V. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. Am J Hum Genet. 2007 Dec;81(6):1169-85. doi: 10.1086/522090. Epub 2007 Oct 22. Citation on PubMed or Free article on PubMed Central
- Chaoui A, Watanabe Y, Touraine R, Baral V, Goossens M, Pingault V, Bondurand N. Identification and functional analysis of SOX10 missense mutations in different subtypes of Waardenburg syndrome. Hum Mutat. 2011 Dec;32(12):1436-49. doi: 10.1002/humu.21583. Epub 2011 Sep 19. Citation on PubMed
- Iso M, Fukami M, Horikawa R, Azuma N, Kawashiro N, Ogata T. SOX10 mutation in Waardenburg syndrome type II. Am J Med Genet A. 2008 Aug 15;146A(16):2162-3. doi: 10.1002/ajmg.a.32403. No abstract available. Citation on PubMed
- Mollaaghababa R, Pavan WJ. The importance of having your SOX on: role of SOX10 in the development of neural crest-derived melanocytes and glia. Oncogene. 2003 May 19;22(20):3024-34. doi: 10.1038/sj.onc.1206442. Citation on PubMed
- Pingault V, Zerad L, Bertani-Torres W, Bondurand N. SOX10: 20 years of phenotypic plurality and current understanding of its developmental function. J Med Genet. 2022 Feb;59(2):105-114. doi: 10.1136/jmedgenet-2021-108105. Epub 2021 Oct 19. Citation on PubMed
- Sham MH, Lui VC, Chen BL, Fu M, Tam PK. Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome. J Med Genet. 2001 Sep;38(9):E30. doi: 10.1136/jmg.38.9.e30. No abstract available. Citation on PubMed or Free article on PubMed Central
- Zhang H, Chen H, Luo H, An J, Sun L, Mei L, He C, Jiang L, Jiang W, Xia K, Li JD, Feng Y. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II. Hum Genet. 2012 Mar;131(3):491-503. doi: 10.1007/s00439-011-1098-2. Epub 2011 Oct 1. Citation on PubMed
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