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RET gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

RET gene

The RET gene provides instructions for producing a protein essential for the development of nerve cells, kidneys, and sperm, and is linked to several hereditary and nonhereditary health conditions.

Normal Function

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.

Health Conditions Related to Genetic Changes

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. RET gene mutations associated with nonsyndromic pheochromocytoma change single amino acids in the RET protein, likely resulting in an overactive protein that triggers cells to grow and divide uncontrollably.

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, leading to the intestinal problems characteristic of the disease.

Multiple endocrine neoplasia

More than 25 mutations in the RET gene are known to cause a form of multiple endocrine neoplasia called type 2. This condition typically involves the development of tumors in two or more of the body's hormone-producing (endocrine) glands. Type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma.

  • Type 2A: Most often results from a mutation that substitutes the amino acid arginine for cysteine at position 634 (Cys634Arg).
  • Type 2B: More than 90 percent of cases are caused by a mutation that replaces methionine with threonine at position 918 (Met918Thr).

These mutations result in an overactive RET protein that transmits signals without needing to attach to growth factors, leading to abnormal cell division and tumor formation.

Lung cancer

MedlinePlus Genetics provides information about lung cancer.

Other cancers

Somatic mutations (acquired during a person's lifetime) in the RET gene have been identified in several nonhereditary (sporadic) cancers. Chromosomal rearrangements involving the RET gene are a common cause of a sporadic form of thyroid cancer called papillary thyroid carcinoma (RET/PTC). Additionally, a nonfamilial form of medullary thyroid carcinoma can be caused by somatic mutations in the RET gene.

Frequently Asked Questions

Testing for RET mutations is usually done with a targeted DNA sequencing panel or a multi‑gene hereditary cancer panel. A blood draw (or sometimes saliva) provides the DNA needed; the lab extracts the DNA and looks for known pathogenic variants in the RET gene.
Sudden, severe headaches, pounding heart rate, high blood pressure, sweating, palpitations, or panic‑like episodes can signal a pheochromocytoma crisis. These signs require immediate evaluation because the tumor can release excess catecholamines that threaten heart and organ function.
While a RET mutation itself cannot be removed, avoiding smoking, limiting alcohol, maintaining a healthy weight, and managing stress can reduce overall cancer risk. Regular imaging surveillance (e.g., MRI or CT of the adrenal glands) is more critical than diet alone for early tumor detection.
Most disease‑causing RET mutations are autosomal dominant, meaning each child has a 50 % chance of inheriting the variant. Some cases arise de novo (new mutation), but if a parent carries the mutation, it is passed to offspring in a 1‑in‑2 likelihood. Genetic counseling is recommended for family planning.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.