Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

EDN3

Reviewed August 2012

What is the official name of the EDN3 gene?

The official name of this gene is “endothelin 3.”

EDN3 is the gene's official symbol. The EDN3 gene is also known by other names, listed below.

What is the normal function of the EDN3 gene?

The EDN3 gene provides instructions for making a protein called endothelin 3. Proteins in the endothelin family are produced in various cells and tissues, where they are involved in the development and function of blood vessels, the production of certain hormones, and the stimulation of cell growth and division.

Endothelin 3 functions by interacting with another protein, endothelin receptor type B (produced from the EDNRB gene), on the surface of cells. During early development before birth, endothelin 3 and endothelin receptor type B together play an important role in 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. In particular, endothelin 3 and its receptor are essential for the formation of nerves in the intestine (enteric nerves) and melanocytes. Melanocytes are cells that produce melanin, a pigment that contributes to skin, hair, and eye color. Melanin is also involved in the normal function of the inner ear.

Does the EDN3 gene share characteristics with other genes?

The EDN3 gene belongs to a family of genes called endogenous ligands (endogenous ligands).

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 EDN3 gene related to health conditions?

Hirschsprung disease - caused by mutations in the EDN3 gene

A small number of mutations in the EDN3 gene cause Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Although Hirschsprung disease is a feature of another disorder called Waardenburg syndrome, type IV (described below), EDN3 gene mutations can also cause Hirschsprung disease in people without Waardenburg syndrome. These mutations change one DNA building block (nucleotide) or insert an additional nucleotide in the gene. Changes in the EDN3 gene disrupt the normal function of endothelin 3, preventing it from playing its usual role in the development of enteric nerves. As a result, these cells do not form normally during embryonic development. A lack of enteric nerves prevents stool from being moved through the intestine normally, leading to severe constipation or intestinal blockage.

Waardenburg syndrome - caused by mutations in the EDN3 gene

Several mutations in the EDN3 gene have been identified in people with Waardenburg syndrome, type IV (also known as Waardenburg-Shah syndrome). This type of Waardenburg syndrome is characterized by changes in skin, hair, and eye coloring; hearing loss; and Hirschsprung disease. EDN3 mutations change single nucleotides in the gene, preventing the production of a functional endothelin 3 protein. Because active endothelin 3 is necessary for the formation of enteric nerves and melanocytes, these cell types 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.

Where is the EDN3 gene located?

Cytogenetic Location: 20q13.2-q13.3

Molecular Location on chromosome 20: base pairs 59,300,443 to 59,325,991

The EDN3 gene is located on the long (q) arm of chromosome 20 between positions 13.2 and 13.3.

The EDN3 gene is located on the long (q) arm of chromosome 20 between positions 13.2 and 13.3.

More precisely, the EDN3 gene is located from base pair 59,300,443 to base pair 59,325,991 on chromosome 20.

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 EDN3?

You and your healthcare professional may find the following resources about EDN3 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 EDN3 gene or gene products?

  • EDN3_HUMAN
  • endothelin 3 precursor
  • ET3
  • HSCR4
  • PPET3
  • Preproendothelin-3
  • RP4-614C15.1
  • WS4B

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 EDN3?

cell ; constipation ; DNA ; embryo ; embryonic ; enteric ; gene ; intestine ; melanin ; melanocytes ; neural crest ; nucleotide ; pigment ; precursor ; protein ; receptor ; stool ; syndrome

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

References

  • Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell. 1994 Dec 30;79(7):1277-85. (http://www.ncbi.nlm.nih.gov/pubmed/8001160?dopt=Abstract)
  • Duan XL, Zhang XS, Li GW. Clinical relationship between EDN-3 gene, EDNRB gene and Hirschsprung's disease. World J Gastroenterol. 2003 Dec;9(12):2839-42. (http://www.ncbi.nlm.nih.gov/pubmed/14669347?dopt=Abstract)
  • OMIM: ENDOTHELIN 3 (http://omim.org/entry/131242)
  • Heuckeroth RO. Finding your way to the end: a tale of GDNF and endothelin-3. Neuron. 2003 Dec 4;40(5):871-3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14659083?dopt=Abstract)
  • Kapur RP, Gershon MD, Milla PJ, Pachnis V. The influence of Hox genes and three intercellular signalling pathways on enteric neuromuscular development. Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:8-13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15065997?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1908)
  • Pingault V, Bondurand N, Lemort N, Sancandi M, Ceccherini I, Hugot JP, Jouk PS, Goossens M. A heterozygous endothelin 3 mutation in Waardenburg-Hirschsprung disease: is there a dosage effect of EDN3/EDNRB gene mutations on neurocristopathy phenotypes? J Med Genet. 2001 Mar;38(3):205-9. (http://www.ncbi.nlm.nih.gov/pubmed/11303518?dopt=Abstract)
  • Shin MK, Levorse JM, Ingram RS, Tilghman SM. The temporal requirement for endothelin receptor-B signalling during neural crest development. Nature. 1999 Dec 2;402(6761):496-501. (http://www.ncbi.nlm.nih.gov/pubmed/10591209?dopt=Abstract)
  • Svensson PJ, Von Tell D, Molander ML, Anvret M, Nordenskjöld A. A heterozygous frameshift mutation in the endothelin-3 (EDN-3) gene in isolated Hirschsprung's disease. Pediatr Res. 1999 May;45(5 Pt 1):714-7. (http://www.ncbi.nlm.nih.gov/pubmed/10231870?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 2012
Published: December 16, 2014