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Proto-oncogene tyrosine-protein kinase receptor Ret is a 1114 amino acid peptide coded by RET (RET protooncogene) at 10q11.2. This is a receptor tyrosine kinase which has two isomers depending upon alternative splicing, that is cleaved into:
  1. Soluble RET kinase fragment
  2. Extracellular cell-membrane anchored RET cadherin 120 kDa fragment

The enzyme is widely involved in involved in regulating cellular mechanisms including cell proliferation, migration and differentiation as well as neuronal navigation. It phosphorylates PTK2/FAK1. It is inhibited by andetanib, cabozantinib, motesanib, sorafenib, sunitinib, and withaferin A.

Well over 100 variants of RET associated with various diseases are known.

Loss of function mutations are found in Hirschsprung disease, while gain of function mutations are found in multiple endocrine neoplasia type 2a and 2b and medullary thyroid carcinoma.

In papillary thyroid carcinoma, a chimeric gene (RET/PTC1) formed through a somatic rearrangement involving the neighboring genes RET and CCDC6 (H4, TST1, PTC1) is the oncogene.

Other genetic conditions due to mutations in RET include renal adysplasia (renal agenesis, renal aplasia, RADYS) and congenital central hypoventilation syndrome (congenital failure of autonomic control, Ondine curse, CCHS).

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