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Genetics Home Reference: your guide to understanding genetic conditions
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SOX9

Reviewed August 2013

What is the official name of the SOX9 gene?

The official name of this gene is “SRY (sex determining region Y)-box 9.”

SOX9 is the gene's official symbol. The SOX9 gene is also known by other names, listed below.

What is the normal function of the SOX9 gene?

The SOX9 gene provides instructions for making a protein that plays a critical role during embryonic development. The SOX9 protein is especially important for the development of the skeleton and reproductive system. This protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this action, the SOX9 protein is called a transcription factor.

Does the SOX9 gene share characteristics with other genes?

The SOX9 gene belongs to a family of genes called SOX (SRY (sex determining region Y)-boxes).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the SOX9 gene related to health conditions?

campomelic dysplasia - caused by mutations in the SOX9 gene

More than 60 mutations involving the SOX9 gene have been found to cause campomelic dysplasia, a disorder that affects the development of the skeleton, reproductive system, and other parts of the body and is often life-threatening in the newborn period. Most cases of campomelic dysplasia are caused by mutations within the SOX9 gene. These mutations prevent the production of the SOX9 protein or result in a protein with impaired ability to function as a transcription factor. About 5 percent of cases are caused by chromosome abnormalities that occur near the SOX9 gene. These chromosome abnormalities disrupt regions of DNA called enhancers that normally regulate the activity of the SOX9 gene. All of these genetic changes prevent the SOX9 protein from properly controlling the genes essential for normal development of the skeleton, reproductive system, and other parts of the body. Abnormal development of these structures causes the signs and symptoms of campomelic dysplasia.

Individuals with milder forms of campomelic dysplasia are more likely to have chromosome abnormalities near the SOX9 gene than mutations within the gene.

isolated Pierre Robin sequence - caused by mutations in the SOX9 gene

Genetic changes that occur near the SOX9 gene cause some cases of isolated Pierre Robin sequence. Individuals with this condition have a small lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and an opening in the roof of the mouth (a cleft palate). These cases of Pierre Robin sequence are described as isolated because they occur without other signs and symptoms.

The genetic changes associated with isolated Pierre Robin sequence are thought to disrupt enhancer regions that normally regulate the activity of the SOX9 gene during development of the lower jaw, which reduces SOX9 gene activity. As a result, the SOX9 protein cannot properly control the genes essential for normal jaw development, causing micrognathia. Underdevelopment of the lower jaw affects placement of the tongue and formation of the palate, leading to glossoptosis and cleft palate.

Where is the SOX9 gene located?

Cytogenetic Location: 17q24.3

Molecular Location on chromosome 17: base pairs 72,121,019 to 72,126,419

The SOX9 gene is located on the long (q) arm of chromosome 17 at position 24.3.

The SOX9 gene is located on the long (q) arm of chromosome 17 at position 24.3.

More precisely, the SOX9 gene is located from base pair 72,121,019 to base pair 72,126,419 on chromosome 17.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SOX9?

You and your healthcare professional may find the following resources about SOX9 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the SOX9 gene or gene products?

  • SOX9_HUMAN
  • SRA1
  • SRY (sex-determining region Y)-box 9 protein
  • transcription factor SOX9

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SOX9?

chromosome ; cleft palate ; DNA ; dysplasia ; embryonic ; enhancer ; gene ; lower jaw ; micrognathia ; palate ; protein ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Amarillo IE, Dipple KM, Quintero-Rivera F. Familial microdeletion of 17q24.3 upstream of SOX9 is associated with isolated Pierre Robin sequence due to position effect. Am J Med Genet A. 2013 May;161A(5):1167-72. doi: 10.1002/ajmg.a.35847. Epub 2013 Mar 26. (http://www.ncbi.nlm.nih.gov/pubmed/23532965?dopt=Abstract)
  • Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nat Genet. 2009 Mar;41(3):359-64. doi: 10.1038/ng.329. Epub 2009 Feb 22. (http://www.ncbi.nlm.nih.gov/pubmed/19234473?dopt=Abstract)
  • Bien-Willner GA, Stankiewicz P, Lupski JR. SOX9cre1, a cis-acting regulatory element located 1.1 Mb upstream of SOX9, mediates its enhancement through the SHH pathway. Hum Mol Genet. 2007 May 15;16(10):1143-56. Epub 2007 Apr 4. (http://www.ncbi.nlm.nih.gov/pubmed/17409199?dopt=Abstract)
  • Fonseca AC, Bonaldi A, Bertola DR, Kim CA, Otto PA, Vianna-Morgante AM. The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9 gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia. BMC Med Genet. 2013 May 7;14:50. doi: 10.1186/1471-2350-14-50. (http://www.ncbi.nlm.nih.gov/pubmed/23648064?dopt=Abstract)
  • Hill-Harfe KL, Kaplan L, Stalker HJ, Zori RT, Pop R, Scherer G, Wallace MR. Fine mapping of chromosome 17 translocation breakpoints > or = 900 Kb upstream of SOX9 in acampomelic campomelic dysplasia and a mild, familial skeletal dysplasia. Am J Hum Genet. 2005 Apr;76(4):663-71. (http://www.ncbi.nlm.nih.gov/pubmed/15717285?dopt=Abstract)
  • Kobayashi A, Chang H, Chaboissier MC, Schedl A, Behringer RR. Sox9 in testis determination. Ann N Y Acad Sci. 2005 Dec;1061:9-17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16467253?dopt=Abstract)
  • Leipoldt M, Erdel M, Bien-Willner GA, Smyk M, Theurl M, Yatsenko SA, Lupski JR, Lane AH, Shanske AL, Stankiewicz P, Scherer G. Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia. Clin Genet. 2007 Jan;71(1):67-75. (http://www.ncbi.nlm.nih.gov/pubmed/17204049?dopt=Abstract)
  • Mead TJ, Wang Q, Bhattaram P, Dy P, Afelik S, Jensen J, Lefebvre V. A far-upstream (-70 kb) enhancer mediates Sox9 auto-regulation in somatic tissues during development and adult regeneration. Nucleic Acids Res. 2013 Apr;41(8):4459-69. doi: 10.1093/nar/gkt140. Epub 2013 Feb 28. (http://www.ncbi.nlm.nih.gov/pubmed/23449223?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6662)
  • Pop R, Zaragoza MV, Gaudette M, Dohrmann U, Scherer G. A homozygous nonsense mutation in SOX9 in the dominant disorder campomelic dysplasia: a case of mitotic gene conversion. Hum Genet. 2005 Jun;117(1):43-53. Epub 2005 Apr 2. (http://www.ncbi.nlm.nih.gov/pubmed/15806394?dopt=Abstract)
  • Smyk M, Obersztyn E, Nowakowska B, Bocian E, Cheung SW, Mazurczak T, Stankiewicz P. Recurrent SOX9 deletion campomelic dysplasia due to somatic mosaicism in the father. Am J Med Genet A. 2007 Apr 15;143A(8):866-70. (http://www.ncbi.nlm.nih.gov/pubmed/17352389?dopt=Abstract)
  • OMIM: SRY-BOX 9 (http://omim.org/entry/608160)
  • Velagaleti GV, Bien-Willner GA, Northup JK, Lockhart LH, Hawkins JC, Jalal SM, Withers M, Lupski JR, Stankiewicz P. Position effects due to chromosome breakpoints that map approximately 900 Kb upstream and approximately 1.3 Mb downstream of SOX9 in two patients with campomelic dysplasia. Am J Hum Genet. 2005 Apr;76(4):652-62. Epub 2005 Feb 22. (http://www.ncbi.nlm.nih.gov/pubmed/15726498?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: December 16, 2014