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Rearranged during Transfection proto-oncogene protein tyrosine kinase (RET)
- Target
- RET
- Molecular classification
- Receptor, Receptor Tyrosine Kinase
01
Overview
The RET proto-oncogene encodes a receptor tyrosine kinase essential for neural crest-derived tissue development and maintenance. Activated by GDNF family ligands, RET regulates cell proliferation, differentiation, survival, migration, and metabolism. Mutations cause Hirschsprung disease (loss-of-function) and various cancers (gain-of-function), making it a therapeutic target for inhibitors in oncology and agonists for neurodegenerative diseases.
- Other names
- RET proto-oncogeneRET51RET43RET9
02
Mechanism of action
Small molecule inhibitors targeting mutant/fusion forms; Agonists (emerging)
03
Biological functions
Signal transductionCell proliferationCell differentiationCell survivalCell migrationMetabolism RegulationNeuronal survival
04
Disease associations
Hirschsprung diseasePapillary thyroid carcinomaMedullary thyroid carcinomaMultiple endocrine neoplasiaPheochromocytomaParathyroid hyperplasiaCentral hypoventilation syndromeRenal agenesisCancer
05
Safety considerations
Off-target effects of inhibitorsResistance to inhibitorsPotential for developmental defects (due to RET's role in embryogenesis)
06
Interacting drugs
RET inhibitors (selective)
07
Biomarkers
RET mutations (e.g., M918T in MTC)RET fusions (e.g., RET/PTC)
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