2IVS, 2IVT, 2IVU, 2IVV, 2X2K, 2X2L, 2X2M, 2X2U, 4CKI, 4CKJ, 4UX8, 5AMN597919713ENSG00000165731ENSMUSG00000030110P07949P35546NM_000323NM_020629NM_020630NM_020975NM_001355216NM_001080780NM_009050NP_065681NP_066124NP_001342145NP_066124.1NP_001074249NP_033076The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signalling molecules.

[5] RET loss of function mutations are associated with the development of Hirschsprung's disease,[6][7] while gain of function mutations are associated with the development of various types of human cancer, including papillary thyroid carcinoma, multiple endocrine neoplasias type 2A and 2B, pheochromocytoma and parathyroid hyperplasia.

Tyr900 and Tyr905 within the activation loop (A-loop) of the kinase domain have been shown to be autophosphorylation sites by mass spectrometry.

[15] Phosphorylation of Tyr905 stabilizes the active conformation of the kinase, which, in turn, results in the autophosphorylation of other tyrosine residues mainly located in the C-terminal tail region of the molecule.

Phosphorylation of Tyr981 and the additional tyrosines Tyr1015, Tyr1062 and Tyr1096, not covered by the above structure, have been shown to be important to the initiation of intracellular signal transduction processes.

Mice deficient in GDNF, GFRα1 or the RET protein itself exhibit severe defects in kidney and enteric nervous system development.

This implicates RET signal transduction as key to the development of normal kidneys and the enteric nervous system.

[16] Activating point mutations in RET can give rise to the hereditary cancer syndrome known as multiple endocrine neoplasia type 2 (MEN 2).