EDN3

Endothelin 3, the protein made by the EDN3 gene, is a member of the endothelin peptide family. Endothelins 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 B, on the surface of cells. During embryonic development, endothelin 3 and endothelin receptor B play an important role in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo and give rise to many different types of cells. In particular, endothelin 3 and its receptor are essential for the normal formation of two cell types from neural crest cells: nerves in the large intestine (enteric nerves) and melanocytes. Melanocytes produce melanin (a pigment that contributes to skin, hair, and eye color) and are important for the normal function of the inner ear.

Waardenburg syndrome - caused by mutations in the EDN3 gene

At least 2 mutations in the EDN3 gene have been identified in people with Waardenburg syndrome, type IV. This type of Waardenburg syndrome is characterized by changes in skin, hair, and eye coloring; hearing loss; and an intestinal disorder called Hirschsprung disease that causes severe constipation or intestinal blockage. EDN3 mutations change single base pairs (the building material of DNA) in the gene, preventing the production of an active 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.

other disorders - caused by mutations in the EDN3 gene

A small number of mutations in the EDN3 gene are responsible for Hirschsprung disease in people without Waardenburg syndrome. These mutations substitute one base pair for another or insert a single base pair in the gene. Changes in the EDN3 gene disrupt the normal function of endothelin 3 and prevent 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 moving through the intestine normally, leading to severe constipation and intestinal blockage.

20q13.2-q13.3

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

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

You and your healthcare professional may find the following resources about EDN3 helpful.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• PubMed - Recent literature
• OMIM - Genetic disorder catalog (2 links)
• Research Resources - Tools for researchers (3 links)

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

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How does a gene make a protein?
• How can gene mutations cause disorders?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

base pair ; constipation ; DNA ; embryo ; enteric ; gene ; hormone ; intestine ; melanin ; melanocytes ; mutation ; neural crest cell ; peptide ; pigment ; protein ; receptor ; sign ; symptom

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