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Reviewed August 2012

What is the official name of the RET gene?

The official name of this gene is “ret proto-oncogene.”

RET is the gene's official symbol. The RET gene is also known by other names, listed below.

Read more about gene names and symbols on the About page.

What is the normal function of 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.

Does the RET gene share characteristics with other genes?

The RET gene belongs to a family of genes called CDH (cadherin superfamily).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? in the Handbook.

How are changes in the RET gene related to health conditions?

Hirschsprung disease - caused by mutations in the RET gene

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. Because these nerves control contractions that move stool through the intestine, their absence leads to the intestinal problems characteristic of Hirschsprung disease.

multiple endocrine neoplasia - caused by mutations in the RET gene

More than 25 mutations in the RET gene are known to cause multiple endocrine neoplasia type 2. Most of these mutations change single protein building blocks (amino acids) in the RET protein. The most common mutation responsible for multiple endocrine neoplasia type 2A substitutes the amino acid arginine for the amino acid cysteine at position 634 (written as Cys634Arg or C634R). Another mutation causes more than 90 percent of cases of multiple endocrine neoplasia type 2B; this change 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 third subtype of multiple endocrine neoplasia type 2.

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; these two disorders rarely occur in the same individual.

nonsyndromic paraganglioma - increased risk from variations of the RET gene

Mutations in the RET gene increase the risk of developing a type of paraganglioma called pheochromocytoma. Paragangliomas are noncancerous (benign) tumors of the nervous system. 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 occur nonsyndromically (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 - associated with the RET gene

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). Another type of thyroid cancer, medullary thyroid carcinoma, also can be caused by somatic mutations in the RET gene.

Where is the RET gene located?

Cytogenetic Location: 10q11.2

Molecular Location on chromosome 10: base pairs 43,572,516 to 43,625,798

The RET gene is located on the long (q) arm of chromosome 10 at position 11.2.

The RET gene is located on the long (q) arm of chromosome 10 at position 11.2.

More precisely, the RET gene is located from base pair 43,572,516 to base pair 43,625,798 on chromosome 10.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about RET?

You and your healthcare professional may find the following resources about RET helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the RET gene or gene products?

  • cadherin family member 12
  • cadherin-related family member 16
  • CDHF12
  • CDHR16
  • HSCR1
  • hydroxyaryl-protein kinase
  • MEN2A
  • MEN2B
  • MTC1
  • PTC
  • rearranged during transfection
  • RET51
  • RET-ELE1
  • ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding RET?

References (23 links)


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

Reviewed: August 2012
Published: February 25, 2013