EDN3-Gen

The EDN3 gene (EDN3 stands for: Endothelin 3) is a protein-coding gene located on chromosome 20q13.32. Alternative splicing results in several transcript variants that code for different isoforms. An important paralog of this gene is EDN1 (endothelin1 gene).

The protein encoded by this gene, endothelin 3, is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides that are involved in a variety of biological functions. The active form of this protein is a 21 amino acid peptide produced from the precursor protein. The active peptide is a ligand for the endothelin receptor type B (EDNRB).

The interaction of this endothelin with EDNRB is essential for the development of neural crest-derived cell lineages such as melanocytes and enteric neurons. Mutations in this gene and in EDNRB have been associated with Hirschsprung disease (HSCR) and Waardenburg syndrome (WS), which are congenital disorders affecting neural crest-derived cells.

Altered expression of this gene is associated with tumorigenesis.

Diseases associated with EDN3 include Waardenburg syndrome, type 4B and Hirschsprung disease 4.

1. Bolk S et al (1996). Endothelin-3 frameshift mutation in congenital central hypoventilation syndrome. Nat Genet 13: 395-396.
2. Bondurand N et al. (2018) News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders. Dev Biol 444 Suppl 1:156-169.
3. Bourgeois C et al (1997). Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ribonucleic acid is generated by alternative splicing of exon 3. J Clin Endocrinol Metab 82: 3116-3123.
4. Hutchins EJ et al. (2018) Migration and diversification of the vagal neural crest. Dev Biol 444 Suppl 1(Suppl 1):98-109.
5. Lahav R et al (1996). Endothelin 3 promotes neural crest cell proliferation and mediates a vast increase in melanocyte number in culture. Proc Natl Acad Sci U.S.A. 93: 3892-3897.
6. Nakano A et al (1997). Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. J. Immunol 159: 1987-1892.