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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed March 2010

What is the official name of the HESX1 gene?

The official name of this gene is “HESX homeobox 1.”

HESX1 is the gene's official symbol. The HESX1 gene is also known by other names, listed below.

What is the normal function of the HESX1 gene?

The HESX1 gene provides instructions for producing a protein that regulates the activity of other genes. On the basis of this action, the HESX1 protein is called a transcription factor. The HESX1 gene is part of a family of homeobox genes, which act during early embryonic development to control the formation of many body structures.

The HESX1 protein plays an important role in early brain development. In particular, it is essential for the formation of the pituitary, which is a gland at the base of the brain that produces several hormones. The HESX1 protein is also necessary for the development of structures at the front of the brain (the forebrain), including the nerves that carry visual information from the eyes to the brain (optic nerves).

The HESX1 protein interacts with other proteins, including the protein produced from the PROP1 gene, during embryonic development. Both the HESX1 protein and the PROP1 protein bind to DNA and control the activity of other genes. The HESX1 protein turns off (represses) genes, while the PROP1 protein turns on (activates) genes. These proteins work together to coordinate the development of certain parts of the brain.

Does the HESX1 gene share characteristics with other genes?

The HESX1 gene belongs to a family of genes called homeobox (homeoboxes).

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? ( in the Handbook.

How are changes in the HESX1 gene related to health conditions?

septo-optic dysplasia - associated with the HESX1 gene

At least five mutations in the HESX1 gene have been identified in people with septo-optic dysplasia. Some of these mutations change single DNA building blocks (base pairs) in the HESX1 gene, while others insert or delete genetic material in the gene. Mutations in this gene alter the function of the HESX1 protein, for example by preventing it from binding to DNA and repressing the activity of other genes. HESX1 gene mutations disrupt the formation and early development of the pituitary gland, optic nerves, and other brain structures. These abnormalities of brain development lead to the characteristic features of septo-optic dysplasia.

Studies suggest that mutations in the HESX1 gene are a rare cause of septo-optic dysplasia.

other disorders - caused by mutations in the HESX1 gene

More than a dozen HESX1 gene mutations have been found to cause underdevelopment (hypoplasia) of the pituitary gland in people without the other characteristic features of septo-optic dysplasia. Pituitary hypoplasia leads to a shortage of hormones needed for growth, reproduction, and other critical body functions. Affected individuals may also have signs and symptoms affecting other parts of the body, including genital abnormalities, vision impairment, distinctive facial features, and extra (supernumerary) fingers.

Mutations in the HESX1 gene lead to the production of a defective or nonfunctional HESX1 protein, which disrupts the formation of the pituitary gland during critical stages of embryonic development. Some mutations prevent the HESX1 protein from binding to DNA and repressing the activity of other genes. Other mutations prevent the HESX1 protein from interacting with the PROP1 protein to coordinate brain development. It is unclear how mutations in the HESX1 gene can cause signs and symptoms affecting other parts of the body.

Where is the HESX1 gene located?

Cytogenetic Location: 3p14.3

Molecular Location on chromosome 3: base pairs 57,197,838 to 57,227,632

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The HESX1 gene is located on the short (p) arm of chromosome 3 at position 14.3.

The HESX1 gene is located on the short (p) arm of chromosome 3 at position 14.3.

More precisely, the HESX1 gene is located from base pair 57,197,838 to base pair 57,227,632 on chromosome 3.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about HESX1?

You and your healthcare professional may find the following resources about HESX1 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 HESX1 gene or gene products?

  • ANF
  • CPHD5
  • homeobox, ES cell expressed 1
  • Rathke pouch homeobox
  • RPX

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding HESX1?

cell ; deficiency ; DNA ; dysplasia ; embryonic ; expressed ; gene ; homeobox ; hormone ; hypoplasia ; pituitary gland ; protein ; reproduction ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Brickman JM, Clements M, Tyrell R, McNay D, Woods K, Warner J, Stewart A, Beddington RS, Dattani M. Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders. Development. 2001 Dec;128(24):5189-99. (
  • Carvalho LR, Woods KS, Mendonca BB, Marcal N, Zamparini AL, Stifani S, Brickman JM, Arnhold IJ, Dattani MT. A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. J Clin Invest. 2003 Oct;112(8):1192-201. (
  • Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Mårtensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. 1998 Jun;19(2):125-33. (
  • Dattani MT, Robinson IC. HESX1 and Septo-Optic Dysplasia. Rev Endocr Metab Disord. 2002 Dec;3(4):289-300. Review. (
  • Kato Y, Kimoto F, Susa T, Nakayama M, Ishikawa A, Kato T. Pituitary homeodomain transcription factors HESX1 and PROP1 form a heterodimer on the inverted TAAT motif. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):168-73. doi: 10.1016/j.mce.2009.10.006. Epub 2009 Oct 29. (
  • McNay DE, Turton JP, Kelberman D, Woods KS, Brauner R, Papadimitriou A, Keller E, Keller A, Haufs N, Krude H, Shalet SM, Dattani MT. HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. J Clin Endocrinol Metab. 2007 Feb;92(2):691-7. Epub 2006 Dec 5. (
  • NCBI Gene (
  • Sobrier ML, Maghnie M, Vié-Luton MP, Secco A, di Iorgi N, Lorini R, Amselem S. Novel HESX1 mutations associated with a life-threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities. J Clin Endocrinol Metab. 2006 Nov;91(11):4528-36. Epub 2006 Aug 29. (
  • Sobrier ML, Netchine I, Heinrichs C, Thibaud N, Vié-Luton MP, Van Vliet G, Amselem S. Alu-element insertion in the homeodomain of HESX1 and aplasia of the anterior pituitary. Hum Mutat. 2005 May;25(5):503. (
  • Tajima T, Hattorri T, Nakajima T, Okuhara K, Sato K, Abe S, Nakae J, Fujieda K. Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. J Clin Endocrinol Metab. 2003 Jan;88(1):45-50. (
  • Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet. 2001 Jan 1;10(1):39-45. (


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? ( in the Handbook.

Reviewed: March 2010
Published: February 8, 2016