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Target intelligence / Profile preview
RET Proto-oncogene Protein Tyrosine Kinase Receptor (RET)
- Target
- RET
- Molecular classification
- Receptor, Receptor tyrosine kinase, Proto-oncogene
01
Overview
The RET proto-oncogene encodes a receptor tyrosine kinase essential for GDNF family ligand signaling. It regulates cell proliferation, differentiation, survival, migration, and metabolism, particularly in nervous system development and maintenance. RET activation requires ligand-coreceptor (GDNF-GFRα) binding, leading to dimerization and autophosphorylation, triggering downstream pathways like MAPK/ERK and PI3K/AKT. Loss-of-function mutations cause Hirschsprung's disease, while gain-of-function mutations and rearrangements are implicated in various cancers, including thyroid carcinomas and other solid tumors. RET is a therapeutic target for small molecule inhibitors in cancer therapy.
- Other names
- RET proto-oncogeneMEN2AMEN2BPTCRET51RET43RET9
02
Mechanism of action
Small molecule inhibitors targeting RET kinase activity; Agonists of RET signaling
03
Biological functions
Signal transductionCell proliferationCell differentiationCell survivalCell migrationOrgan developmentNeuron maintenance
04
Disease associations
Hirschsprung's diseaseCentral hypoventilation syndromeRenal agenesisPapillary thyroid carcinomaMedullary thyroid carcinomaMultiple endocrine neoplasia type 2AMultiple endocrine neoplasia type 2BPheochromocytomaParathyroid hyperplasiaLung cancerColorectal cancerBreast cancerSalivary gland cancerObesityNeurodegenerative diseases
05
Safety considerations
Therapy resistance due to mutationsOff-target effects of kinase inhibitors
06
Biomarkers
RET mutations (e.g., M918T, exons 10-11, exon 15)RET/PTC fusion transcripts
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