Summary of RET
The RET gene encodes a protein that is involved in signaling within cells. It is also necessary for normal kidney development and the production of sperm. It is associated with higher risk for cancer, constipation, blockage of the intestines, and problems with the thyroid (R).
The Function of RET
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.
Recommended name:Proto-oncogene tyrosine-protein kinase receptor Ret
Alternative name(s):Cadherin family member 12
- RS17158558 (RET) ??
- RS1799939 (RET) ??
- RS1800858 (RET) ??
- RS1800860 (RET) ??
- RS1800861 (RET) ??
- RS1800862 (RET) ??
- RS1800863 (RET) ??
- RS1864400 (RET) ??
- RS2075912 (RET) ??
- RS2435357 (RET) ??
- RS2472737 (RET) ??
- RS2505535 (RET) ??
- RS2506030 (RET) ??
- RS2742234 (RET) ??
- RS3026785 (RET) ??
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Top Gene-Substance Interactions
RET Interacts with These Diseases
Substances That Increase RET
Substances That Decrease RET
Hirschsprung disease Mutations in the RET gene are the most common genetic cause of Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. More than 200 RET gene mutations are known to cause this condition. These genetic changes result in a nonfunctional version of the RET protein that cannot interact with growth factors or transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. These nerves control contractions that move stool through the intestine, and their absence leads to the intestinal problems characteristic of Hirschsprung disease. lung cancer Genetics Home Reference provides information about lung cancer. multiple endocrine neoplasia More than 25 mutations in the RET gene are known to cause a form of multiple endocrine neoplasia called type 2. Multiple endocrine neoplasia typically involves the development of tumors in two or more of the body's hormone-producing glands, called endocrine glands. These tumors can be noncancerous or cancerous. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma. These subtypes are distinguished by their characteristic signs and symptoms and risk of specific tumors. Most of the RET gene mutations that cause multiple endocrine neoplasia type 2 change single protein building blocks (amino acids) in the RET protein. Type 2A most often results from a mutation that substitutes the amino acid arginine for the amino acid cysteine at position 634 (written as Cys634Arg or C634R). More than 90 percent of cases of type 2B are caused by a mutation that replaces the amino acid methionine with the amino acid threonine at position 918 (written as Met918Thr or M918T). Several amino acid substitutions can cause familial medullary thyroid carcinoma. The mutations responsible for multiple endocrine neoplasia type 2 result in an overactive RET protein that can transmit signals without first attaching to growth factors outside the cell. The overactive protein likely triggers cells to grow and divide abnormally, which can lead to the formation of tumors in the endocrine system and other tissues. The overactivating RET gene mutations that cause multiple endocrine neoplasia type 2 are very different from the inactivating mutations that cause Hirschsprung disease (described above); these two disorders rarely occur in the same individual. nonsyndromic paraganglioma Mutations in the RET gene increase the risk of developing a type of paraganglioma called pheochromocytoma. Paragangliomas are tumors of the nervous system that are usually noncancerous (benign). Pheochromocytomas specifically affect the adrenal glands, which are small hormone-producing glands located on top of each kidney. Pheochromocytomas are a feature of multiple endocrine neoplasia type 2, but they can also be nonsyndromic, which means they occur without the other signs and symptoms of the syndrome. RET gene mutations associated with nonsyndromic pheochromocytoma change single amino acids in the RET protein. As in multiple endocrine neoplasia type 2, the mutations likely result in an overactive RET protein that can trigger cells to grow and divide uncontrollably and can lead to the formation of tumors. other cancers Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic changes in the RET gene have been identified in several nonhereditary (sporadic) cancers. Chromosomal rearrangements involving the RET gene are one of the most common causes of a sporadic form of thyroid cancer called papillary thyroid carcinoma (also known as RET/PTC). Additionally, a nonfamilial form of medullary thyroid carcinoma (a type of thyroid cancer that can also occur as part of multiple endocrine neoplasia) can be caused by somatic mutations in the RET gene.
The RET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine (enteric neurons) and the portion of the nervous system that controls involuntary body functions such as heart rate (the autonomic nervous system). The RET protein is also necessary for normal kidney development and the production of sperm (spermatogenesis). The RET protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning of the protein allows it to interact with specific factors outside the cell and to receive signals that help the cell respond to its environment. When molecules that stimulate growth and development (growth factors) attach to the RET protein, a complex cascade of chemical reactions inside the cell is triggered. These reactions instruct the cell to undergo certain changes, such as dividing or maturing to take on specialized functions.
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors affect gene expression:
Positively regulated by NKX2-1, PHOX2B, SOX10 and PAX3.
Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation.
- Protein Tyrosine Kinase Activity
- Transmembrane Receptor Protein Tyrosine Kinase Activity
- Receptor Activity
- Ras Guanyl-Nucleotide Exchange Factor Activity
- Calcium Ion Binding
- Atp Binding
- Mapk Cascade
- Ureteric Bud Development
- Neural Crest Cell Migration
- Embryonic Epithelial Tube Formation
- Protein Phosphorylation
- Activation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Homophilic Cell Adhesion Via Plasma Membrane Adhesion Molecules
- Neuron Cell-Cell Adhesion
- Signal Transduction
- Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
- Posterior Midgut Development
- Positive Regulation Of Neuron Projection Development
- Positive Regulation Of Neuron Maturation
- Regulation Of Cell Adhesion
- Positive Regulation Of Cell Migration
- Membrane Protein Proteolysis
- Positive Regulation Of Cell Adhesion Mediated By Integrin
- Ureter Maturation
- Neuron Maturation
- Positive Regulation Of Cell Size
- Positive Regulation Of Transcription, Dna-Templated
- Response To Pain
- Enteric Nervous System Development
- Regulation Of Axonogenesis
- Retina Development In Camera-Type Eye
- Peyer's Patch Morphogenesis
- Cellular Response To Retinoic Acid
- Positive Regulation Of Metanephric Glomerulus Development
- Lymphocyte Migration Into Lymphoid Organs
- Positive Regulation Of Serine Phosphorylation Of Stat3 Protein
- Positive Regulation Of Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand