The EDNRB gene provides instructions for making a protein called endothelin receptor type B. This protein is located on the surface of cells and functions as a signaling mechanism, transmitting information from outside the cell to inside the cell. The receptor interacts with proteins called endothelins to regulate several critical biological processes, including the development and function of blood vessels, the production of certain hormones, and the stimulation of cell growth and division (proliferation).
Endothelin 3 (produced from the EDN3 gene) is one of the proteins that interacts with endothelin receptor type B. During early development before birth (embryonic development), 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 endothelin receptor type B are essential for the formation of nerves in the intestine (enteric nerves) and for the production of specialized cells called melanocytes. Melanocytes produce melanin, a pigment that contributes to skin, hair, and eye color. Melanin is also involved in the normal function of the inner ear.
Health Conditions Related to Genetic Changes
Variants (also known as mutations) in the EDNRB gene have been found to cause Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Although Hirschsprung disease is a feature of another condition called Waardenburg syndrome type IV (described below), EDNRB gene variants can also cause Hirschsprung disease in people without Waardenburg syndrome. People with a variant in one of the two copies of the EDNRB gene tend to develop Hirschsprung disease, while people with variants in both copies of the gene usually develop Waardenburg syndrome type IV. Most of these variants change single DNA building blocks (nucleotides) in the gene. Changes in the EDNRB gene disrupt the normal function of endothelin receptor type B, 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.More About This Health Condition
Variants in the EDNRB gene have been identified in people with Waardenburg syndrome type IV (also known as Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome). This type of Waardenburg syndrome is characterized by changes in skin, hair, and eye coloring; hearing loss; and Hirschsprung disease (described above). Variants in the EDNRB gene disrupt the normal function of endothelin receptor type B or lead to the production of an abnormally small, nonfunctional version of the protein. Because the receptor 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.More About This Health Condition
Several studies have suggested that inherited variations in the EDNRB gene may be associated with an increased risk of melanoma, a common form of skin cancer that begins in melanocytes. However, other studies have not shown this association, and this gene's role in cancer risk remains unclear.
Other Names for This Gene
- endothelin receptor, non-selective type
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Amiel J, Attie T, Jan D, Pelet A, Edery P, Bidaud C, Lacombe D, Tam P, Simeoni J, Flori E, Nihoul-Fekete C, Munnich A, Lyonnet S. Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease. Hum Mol Genet. 1996 Mar;5(3):355-7. doi: 10.1093/hmg/5.3.355. Citation on PubMed
- Barlow A, de Graaff E, Pachnis V. Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron. 2003 Dec 4;40(5):905-16. doi: 10.1016/s0896-6273(03)00730-x. Citation on PubMed
- 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. doi: 10.1016/0092-8674(94)90018-3. Citation on PubMed
- 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. doi: 10.3748/wjg.v9.i12.2839. Citation on PubMed or Free article on PubMed Central
- 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. doi: 10.1136/jmg.38.3.205. No abstract available. Citation on PubMed or Free article on PubMed Central
- Pla P, Larue L. Involvement of endothelin receptors in normal and pathological development of neural crest cells. Int J Dev Biol. 2003 Jun;47(5):315-25. Citation on PubMed
- Sanchez-Mejias A, Fernandez RM, Lopez-Alonso M, Antinolo G, Borrego S. New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. Genet Med. 2010 Jan;12(1):39-43. doi: 10.1097/GIM.0b013e3181c371b0. Citation on PubMed
- Soufir N, Meziani R, Lacapere JJ, Bertrand G, Fumeron F, Bourillon A, Gerard B, Descamps V, Crickx B, Ollivaud L, Archimbaud A, Lebbe C, Basset-Seguin N, Saiag P, Grandchamp B; Investigators of the Melan-Cohort. Association between endothelin receptor B nonsynonymous variants and melanoma risk. J Natl Cancer Inst. 2005 Sep 7;97(17):1297-301. doi: 10.1093/jnci/dji253. Citation on PubMed
- Spica T, Fargnoli MC, Hetet G, Bertrand G, Formicone F, Descamps V, Wolkenstein P, Dupin N, Lebbe C, Basset-Seguin N, Saiag P, Cambien F, Grandchamp B, Peris K, Soufir N. EDNRB gene variants and melanoma risk in two southern European populations. Clin Exp Dermatol. 2011 Oct;36(7):782-7. doi: 10.1111/j.1365-2230.2011.04062.x. Epub 2011 Apr 20. Citation on PubMed
- Thirumaran RK, Thoelke A, Ugurel S, Hemminki K, Schadendorf D, Kumar R. Re: Association between endothelin receptor B nonsynonymous variants and melanoma risk. J Natl Cancer Inst. 2006 Sep 6;98(17):1252-3; author reply 1253. doi: 10.1093/jnci/djj336. No abstract available. Citation on PubMed