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 ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

URL of this page: https://medlineplus.gov/genetics/gene/otx2/

OTX2 gene

orthodenticle homeobox 2

Normal Function

The OTX2 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 OTX2 gene is part of a family of homeobox genes, which act during early embryonic development to control the formation of many body structures.

The OTX2 protein plays a critical role in regulating the genes that are involved in the development of the eyes and related structures, such as the nerves that carry visual information from the eyes to the brain (optic nerves). The OTX2 protein is also involved in brain development, including the formation of the pituitary gland at the base of the brain. The pituitary gland produces hormones that help control growth, reproduction, and other critical body functions.

Health Conditions Related to Genetic Changes

Septo-optic dysplasia

MedlinePlus Genetics provides information about Septo-optic dysplasia

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

Anophthalmia/Microphthalmia

Variants (also called mutations) in the OTX2 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). People who have OTX2 gene variants may have anophthalmia or microphthalmia alone (isolated anophthalmia or microphthalmia), or they may have anophthalmia or microphthalmia as part of a syndrome that affects multiple parts of the body (syndromic anophthalmia or microphthalmia). Additional signs and symptoms of syndromic anophthalmia or microphthalmia can include missing pieces of tissue in structures that form the eye (coloboma), intellectual disabilities, and abnormalities of the pituitary gland. The signs and symptoms that are associated with OTX2 gene variants can vary, even among members of the same family.

Many different variants in the OTX2 gene have been associated with anophthalmia and microphthalmia. Some OTX2 gene variants cause cells to produce an abnormally short version of the OTX2 protein, while other variants lead to the substitution of one protein building block (amino acid) for another in the OTX2 protein. These genetic changes disrupt the protein's ability to regulate the genes that are essential for the normal development of the eyes, which can lead to anophthalmia or microphthalmia. 

More About This Health Condition

Other disorders

Variants in the OTX2 gene may contribute to the otocephaly-dysgnathia complex, which is characterized by low-set ears, an absent or underdeveloped lower jaw, a small mouth (microstomia), and an unusually small tongue (microglossia). Additional signs and symptoms that have been associated with the otocephaly-dysgnathia complex include: eye abnormalities, such as anophthalmia and microphthalmia; intellectual disabilities; and an underdeveloped pituitary gland. Though variants in the OTX2 gene may contribute to the development of the otocephaly-dysgnathia complex, researchers are working to learn more about the cause of this disorder.

Research has suggested that the OTX2 gene may also play a role in the progression of the most aggressive forms of medulloblastoma, a type of cancerous brain tumor that occurs during childhood. In these cases, the OTX2 protein does not act as a transcription factor. Instead, it works with proteins called splicing factors, which help process messenger RNA (mRNA). mRNA is a chemical cousin of DNA, and it serves as a genetic blueprint for making proteins. The OTX2 protein helps cut and rearrange the mRNA blueprint to produce different versions of proteins (alternative splicing), some of which allow tumor cells to grow. Researchers do not fully understand why the OTX2 protein, which normally acts as a transcription factor, sometimes acts in this different role.

Other Names for This Gene

  • CPHD6
  • MCOPS5

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

  • Chassaing N, Sorrentino S, Davis EE, Martin-Coignard D, Iacovelli A, Paznekas W, Webb BD, Faye-Petersen O, Encha-Razavi F, Lequeux L, Vigouroux A, Yesilyurt A, Boyadjiev SA, Kayserili H, Loget P, Carles D, Sergi C, Puvabanditsin S, Chen CP, Etchevers HC, Katsanis N, Mercer CL, Calvas P, Jabs EW. OTX2 mutations contribute to the otocephaly-dysgnathia complex. J Med Genet. 2012 Jun;49(6):373-9. doi: 10.1136/jmedgenet-2012-100892. Epub 2012 May 10. Citation on PubMed
  • Dateki S, Fukami M, Sato N, Muroya K, Adachi M, Ogata T. OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. J Clin Endocrinol Metab. 2008 Oct;93(10):3697-702. doi: 10.1210/jc.2008-0720. Epub 2008 Jul 15. Citation on PubMed
  • Dateki S, Kosaka K, Hasegawa K, Tanaka H, Azuma N, Yokoya S, Muroya K, Adachi M, Tajima T, Motomura K, Kinoshita E, Moriuchi H, Sato N, Fukami M, Ogata T. Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype. J Clin Endocrinol Metab. 2010 Feb;95(2):756-64. doi: 10.1210/jc.2009-1334. Epub 2009 Dec 4. Citation on PubMed
  • Diaczok D, Romero C, Zunich J, Marshall I, Radovick S. A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency. J Clin Endocrinol Metab. 2008 Nov;93(11):4351-9. doi: 10.1210/jc.2008-1189. Epub 2008 Aug 26. Citation on PubMed or Free article on PubMed Central
  • 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
  • Lu Y, Labak CM, Jain N, Purvis IJ, Guda MR, Bach SE, Tsung AJ, Asuthkar S, Velpula KK. OTX2 expression contributes to proliferation and progression in Myc-amplified medulloblastoma. Am J Cancer Res. 2017 Mar 1;7(3):647-656. eCollection 2017. Citation on PubMed
  • Patat O, van Ravenswaaij-Arts CM, Tantau J, Corsten-Janssen N, van Tintelen JP, Dijkhuizen T, Kaplan J, Chassaing N. Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2. Mol Syndromol. 2013 Sep;4(6):302-5. doi: 10.1159/000353727. Epub 2013 Jul 9. Citation on PubMed
  • 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
  • Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, Ruddle P, Hurst J, Collin JR, Salt A, Cooper ST, Thompson PJ, Sisodiya SM, Williamson KA, Fitzpatrick DR, van Heyningen V, Hanson IM. Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet. 2005 Jun;76(6):1008-22. doi: 10.1086/430721. Epub 2005 Apr 21. Citation on PubMed or Free article on PubMed Central
  • Saulnier O, Zagozewski J, Liang L, Hendrikse LD, Layug P, Gordon V, Aldinger KA, Haldipur P, Borlase S, Coudiere-Morrison L, Cai T, Martell E, Gonzales NM, Palidwor G, Porter CJ, Richard S, Sharif T, Millen KJ, Doble BW, Taylor MD, Werbowetski-Ogilvie TE. A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing. Nat Cell Biol. 2024 Aug;26(8):1233-1246. doi: 10.1038/s41556-024-01460-5. Epub 2024 Jul 18. Citation on PubMed
  • Tajima T, Ohtake A, Hoshino M, Amemiya S, Sasaki N, Ishizu K, Fujieda K. OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. J Clin Endocrinol Metab. 2009 Jan;94(1):314-9. doi: 10.1210/jc.2008-1219. Epub 2008 Oct 14. Citation on PubMed
  • Wyatt A, Bakrania P, Bunyan DJ, Osborne RJ, Crolla JA, Salt A, Ayuso C, Newbury-Ecob R, Abou-Rayyah Y, Collin JR, Robinson D, Ragge N. Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma. Hum Mutat. 2008 Nov;29(11):E278-83. doi: 10.1002/humu.20869. Citation on PubMed

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.