RET and NTRK1 proto-oncogenes in human diseases

J Cell Physiol. 2003 May;195(2):168-86. doi: 10.1002/jcp.10252.


RET and NTRK1 are receptor tyrosine kinase (RTK) proteins which play a role in the development and maturation of specific component of the nervous system. Their alterations have been associated to several human diseases, including some forms of cancer and developmental abnormalities. These features have contributed to the concept that one gene can be responsible for more than one disease. Moreover, both genes encoding for the two RTKs show genetic alterations that belong to either "gain of function" or "loss of function" class of mutations. In fact, receptor rearrangements or point mutations convert RET and NTRK1 in dominantly acting transforming genes leading to thyroid tumors, whereas inactivating mutations, associated with Hirschsprung's disease (HSCR) and congenital insensitivity to pain with anhidrosis (CIPA), impair RET and NTRK1 functions, respectively. In this review we have summarized the main features of the two receptors, their physiological and pathological roles. In addition, we attempted to identify the correlations between the different genetic alterations and the related pathogenetic mechanisms.

Publication types

  • Review

MeSH terms

  • Animals
  • Drosophila Proteins*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / metabolism
  • Genetic Diseases, Inborn / physiopathology
  • Hereditary Sensory and Autonomic Neuropathies / genetics
  • Hereditary Sensory and Autonomic Neuropathies / metabolism
  • Hereditary Sensory and Autonomic Neuropathies / physiopathology
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / metabolism
  • Hirschsprung Disease / physiopathology
  • Humans
  • Mutation / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, trkA / genetics*
  • Receptor, trkA / metabolism
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / physiopathology


  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Ret protein, Drosophila