Endothelin receptor type B (EDNRB) is expressed in most tissues. Mutations in this receptor are responsible for Hirschsprung disease type 2, a multigenic disorder with phenotypes such as bicolored irides, megacolon, hypopigmentation, and hearing loss. EDNRB has similar affinity for all three endothelins and activates a phosphatidylinositol-calcium second messenger system. A splice variant, termed SVR, has been described; the sequence of the ETB-SVR receptor is identical to ET-B receptor, with the exception of the intracellular C-terminal domain. While both splice variants bind endothelin ET1, they exhibit different responses, which suggests that they may be functionally distinct. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804