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The GDNF family members (GDNF, neurturin and persephin) signal through multicomponent receptors that consist of the Ret receptor tyrosine kinase and one of four glycosyl-phosphatidylinositol (GPI)-linked ligand-binding subunits (GFR alpha-1 -4). GFR alpha-1, -2, and -4 are the preferred ligand-binding subunits for GDNF, neurturin and persephin, respectively. The Ret tyrosine-kinase receptor is encoded by the c-ret proto-oncogene. Human and mouse Ret share 83% amino acid sequence homology.
Mutations in this gene are associated with the disorders multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, Hirschsprung disease, and medullary thyroid carcinoma. Two transcript variants encoding different isoforms have been found for this gene.
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