Health Topics

Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( Lock Locked padlock icon ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

You Are Here:
Home →
Genetics →
Genes →
SOX2 gene
URL of this page: https://medlineplus.gov/genetics/gene/sox2/

SOX2 gene

SRY-box transcription factor 2

Normal Function

The SOX2 gene provides instructions for making a type of protein called a transcription factor. Transcription factors attach (bind) to specific regions of DNA and help regulate the activity of other genes.

The SOX2 protein plays a critical role in regulating the genes that are involved in the formation of many different tissues and organs during embryonic development. The SOX2 protein is especially important for the development of the eyes. 

Health Conditions Related to Genetic Changes

Anophthalmia/Microphthalmia

Many different variants (also called mutations) in the SOX2 gene can cause one or both eyes to be absent (anophthalmia) or underdeveloped and abnormally small (microphthalmia). Because both conditions are characterized by impaired eye development, anophthalmia and microphthalmia are often considered to be related disorders (anophthalmia/microphthalmia). SOX2 gene variants are the most common genetic cause of anophthalmia and microphthalmia, but these variants are most common in people who have anophthalmia or severe microphthalmia that occurs in both eyes (bilateral).  

Many of the variants that cause anophthalmia and severe microphthalmia are known as "loss-of-function variants" because they reduce the activity of the SOX2 protein or decrease the amount of protein that is produced by the cells. Loss-of-function variants in the SOX2 gene reduce the amount of SOX2 protein that is available to regulate the early development of the eyes, which can lead to anophthalmia or microphthalmia. Researchers are working to determine why some people with SOX2 gene variants only develop eye abnormalities, while others develop eye abnormalities with additional signs and symptoms.

More About This Health Condition

Anophthalmia/microphthalmia-esophageal atresia syndrome

Several variants in the SOX2 gene have been found to cause anophthalmia/microphthalmia-esophageal atresia (AEG) syndrome, a rare disorder that is characterized by the abnormal development of the eyes and other parts of the body, including the tube that carries food from the mouth to the stomach (esophagus). People with this condition often have anophthalmia or microphthalmia in addition to esophageal defects, which can include a blockage of the esophagus (esophageal atresia). 

Loss-of-function variants cause AEG syndrome. Without enough functional SOX2 protein, the genes that are essential for the normal development of the eyes and other parts of the body cannot be regulated properly. The abnormal development of these structures causes the signs and symptoms of AEG syndrome.

More About This Health Condition

Coloboma

MedlinePlus Genetics provides information about Coloboma

More About This Health Condition

Combined pituitary hormone deficiency

MedlinePlus Genetics provides information about Combined pituitary hormone deficiency

More About This Health Condition

Peters anomaly

MedlinePlus Genetics provides information about Peters anomaly

More About This Health Condition

Septo-optic dysplasia

MedlinePlus Genetics provides information about Septo-optic dysplasia

More About This Health Condition

Other disorders

Variants in the SOX2 gene have been associated with hypogonadotropic hypogonadism, which is caused by a lack of certain hormones that direct sexual development. Researchers are working to learn more about this association. In some cases, the associated SOX2 variant results in the substitution of one protein building block (amino acid) for another in the SOX2 protein. In other cases, the SOX2 variant causes cells to produce a shortened version of the SOX2 protein that does not function properly. People with this type of variant are also more likely to have eye abnormalities.

Other Names for This Gene

  • ANOP3
  • MCOPS3
  • SRY box 2
  • SRY-related HMG-box gene 2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Alatzoglou KS, Kelberman D, Dattani MT. The role of SOX proteins in normal pituitary development. J Endocrinol. 2009 Mar;200(3):245-58. doi: 10.1677/JOE-08-0447. Epub 2008 Dec 12. Citation on PubMed
  • Bakrania P, Robinson DO, Bunyan DJ, Salt A, Martin A, Crolla JA, Wyatt A, Fielder A, Ainsworth J, Moore A, Read S, Uddin J, Laws D, Pascuel-Salcedo D, Ayuso C, Allen L, Collin JR, Ragge NK. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. Br J Ophthalmol. 2007 Nov;91(11):1471-6. doi: 10.1136/bjo.2007.117929. Epub 2007 May 23. Citation on PubMed or Free article on PubMed Central
  • Cassin J, Stamou MI, Keefe KW, Sung KE, Bojo CC, Tonsfeldt KJ, Rojas RA, Ferreira Lopes V, Plummer L, Salnikov KB, Keefe DL Jr, Ozata M, Genel M, Georgopoulos NA, Hall JE, Crowley WF Jr, Seminara SB, Mellon PL, Balasubramanian R. Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms. JCI Insight. 2023 Feb 8;8(3):e164324. doi: 10.1172/jci.insight.164324. Citation on PubMed
  • Chesneau B, Aubert-Mucca M, Fremont F, Pechmeja J, Soler V, Isidor B, Nizon M, Dollfus H, Kaplan J, Fares-Taie L, Rozet JM, Busa T, Lacombe D, Naudion S, Amiel J, Rio M, Attie-Bitach T, Lesage C, Thouvenin D, Odent S, Morel G, Vincent-Delorme C, Boute O, Vanlerberghe C, Dieux A, Boussion S, Faivre L, Pinson L, Laffargue F, Le Guyader G, Le Meur G, Prieur F, Lambert V, Laudier B, Cottereau E, Ayuso C, Corton-Perez M, Bouneau L, Le Caignec C, Gaston V, Jeanton-Scaramouche C, Dupin-Deguine D, Calvas P, Chassaing N, Plaisancie J. First evidence of SOX2 mutations in Peters' anomaly: Lessons from molecular screening of 95 patients. Clin Genet. 2022 May;101(5-6):494-506. doi: 10.1111/cge.14123. Epub 2022 Feb 27. Citation on PubMed
  • Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia. Nat Genet. 2003 Apr;33(4):461-3. doi: 10.1038/ng1120. Epub 2003 Mar 3. Citation on PubMed
  • Harding P, Moosajee M. The Molecular Basis of Human Anophthalmia and Microphthalmia. J Dev Biol. 2019 Aug 14;7(3):16. doi: 10.3390/jdb7030016. Citation on PubMed
  • Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Lovell-Badge R, Robinson IC, Gerrelli D, Dattani MT. SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. J Clin Endocrinol Metab. 2008 May;93(5):1865-73. doi: 10.1210/jc.2007-2337. Epub 2008 Feb 19. Citation on PubMed or Free article on PubMed Central
  • Kelberman D, Rizzoti K, Avilion A, Bitner-Glindzicz M, Cianfarani S, Collins J, Chong WK, Kirk JM, Achermann JC, Ross R, Carmignac D, Lovell-Badge R, Robinson IC, Dattani MT. Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans. J Clin Invest. 2006 Sep;116(9):2442-55. doi: 10.1172/JCI28658. Epub 2006 Aug 24. Citation on PubMed or Free article on PubMed Central
  • Plaisancie J, Ceroni F, Holt R, Zazo Seco C, Calvas P, Chassaing N, Ragge NK. Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia. Hum Genet. 2019 Sep;138(8-9):799-830. doi: 10.1007/s00439-019-01977-y. Epub 2019 Feb 14. Citation on PubMed
  • Tziaferi V, Kelberman D, Dattani MT. The role of SOX2 in hypogonadotropic hypogonadism. Sex Dev. 2008;2(4-5):194-9. doi: 10.1159/000152035. Epub 2008 Nov 5. Citation on PubMed
  • Williamson KA, FitzPatrick DR. The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur J Med Genet. 2014 Aug;57(8):369-80. doi: 10.1016/j.ejmg.2014.05.002. Epub 2014 May 22. Citation on PubMed
  • Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, Keng WT, Sharkey FH, McGill N, Hill CJ, Schneider A, Messina M, Turnpenny PD, Fantes JA, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet. 2006 May 1;15(9):1413-22. doi: 10.1093/hmg/ddl064. Epub 2006 Mar 16. Citation on PubMed
  • Williamson KA, Yates TM, FitzPatrick DR. SOX2 Disorder. 2006 Feb 23 [updated 2020 Jul 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1300/ Citation on PubMed
  • Zhou J, Kherani F, Bardakjian TM, Katowitz J, Hughes N, Schimmenti LA, Schneider A, Young TL. Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. Mol Vis. 2008 Mar 24;14:583-92. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.