The RET gene gives cells instructions for a signaling protein that helps guide the development of nerves, the thyroid, the kidneys, and the bowel. This gene plays an important role in how cells grow and communicate. If RET signaling becomes too active, it can lead to conditions such as multiple endocrine neoplasia type 2 and medullary thyroid cancer. If the gene does not work well enough, some people are born with Hirschsprung disease, where part of the bowel cannot move stool normally.
What is a gene?
A gene is a stretch of DNA that carries instructions cells use to make molecules or regulate activities in the body. Some genes hold the code for proteins, the functional parts of cells. Other genes mainly guide when certain activities take place, where they occur, and how strongly they operate. Together, genes affect how the body grows and works, and they can influence how you respond to food, stress, or medicines. For a closer look at this subject, you can find more in the LearnHub.
Overview
RETGene function
What if the gene works
The RET gene helps cells receive growth signals during early development. It is especially important for nerve cells, the digestive tract's nerve network, and kidney formation.
Risk
What if the gene does not work
RET variants can cause inherited medullary thyroid cancer, sometimes with adrenal tumors, or developmental conditions such as Hirschsprung disease. Milder and severe variants can affect which features appear, when they begin, and how strongly RET signaling is reduced or increased.
Treatment
What does that mean for your treatment
For cancers driven by activating variants in the RET gene or fusions involving the RET gene, drugs that target RET, including selpercatinib and pralsetinib, can guide treatment choices in current guidelines. In inherited RET related endocrine cancer syndromes, the specific variant also helps guide the timing of preventive thyroid surgery. Loss of function conditions linked to the RET gene do not currently have a RET specific drug treatment.
Conditions associated with RET
Gene function
What if the gene works
Your body uses the RET gene to pass signals from the surface of certain cells to the inside. These signals are especially important before birth, helping form nerve networks and parts of the urinary system. Understanding how the RET gene works also shows how cells keep growth and survival signals organized.
The RET gene helps certain cells receive signals at the cell surface and turn them into clear instructions inside the cell. This supports normal cell growth, survival, and timing during development.
This gene guides immature nerve cells as they grow, move, and settle into the right places. This is part of how the body builds stable nerve pathways before birth.
In the developing digestive tract, the RET gene helps form the nerve network that coordinates movement of food through the gut. When RET is working properly, these nerve cells can spread through the intestine in an organized way.
During early development, RET supports signals that shape the kidneys and parts of the urinary tract. These signals help growing tissues branch and connect in the usual pattern.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help create normal human diversity, such as differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some cases, though, a variant can change how a gene functions more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the RET gene can change the receptor’s shape, keep it from reaching the cell surface, weaken its signaling activity, or switch it on when it should be quiet. This shows how RET gene variants affect protein function, from milder changes to more disruptive variants. Activating variants often drive more constant signaling, while loss-of-function variants reduce signaling or cell-surface delivery. That difference can influence how early related conditions appear and how broad the features are.
How variants are linked to conditions
Pathogenic variants in the RET gene can cause multiple endocrine neoplasia type 2, including MEN2A and MEN2B, and are strongly linked to medullary thyroid cancer. Some people with an inherited RET gene variant also develop pheochromocytoma, and MEN2A may include parathyroid disease. Separate RET gene variants are associated with Hirschsprung disease. In cancer care, acquired RET changes, including fusions, are found in some thyroid cancers and non-small cell lung cancers.
A variant is not necessarily a diagnosis
Variants in genes are a normal part of human biology and are widely seen in the general population. Most have no direct impact on health and simply reflect natural human diversity. For many genes, carrying a variant connected with a condition indicates a possible association rather than a definite diagnosis, especially when more than one gene and environmental factors play a role. In some cases, though, a single well-characterized variant in a specific gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
With RET, risk is driven mainly by the specific inherited variant and family history. Some RET changes carry a higher chance of medullary thyroid cancer or adrenal gland tumors and can affect the age they appear. Lifestyle changes have not been shown to remove this risk, so regular monitoring matters most.
Inheritance of RET variants
Most well-established RET-related conditions follow autosomal dominant inheritance. In practical terms, RET gene inheritance means a parent carrying a disease-causing RET variant can pass it to each child with a 50% chance, whether the child is a son or a daughter. Some people with a RET-related condition have a new (de novo) variant, so it was not inherited from either parent.
What does my RET result mean for my family?
A RET result can matter for close relatives because some RET-related conditions run in families in a dominant way, so parents, siblings, and children may also carry the same change. This is especially important for inherited thyroid cancer and related hormone gland conditions linked to RET. Some RET changes can also be new in one person, particularly in certain cases, so a parent does not always have the same result. The family impact can differ depending on the exact RET change and the condition involved.
Genetic information
Genetic testing
How you find out about variants
To find out about RET gene variants, genetic testing uses a blood or saliva sample. A lab reads the DNA code in the RET gene to look for specific variants, confirm a family finding, or help clarify whether a condition linked to the RET gene is present.
When should I consider getting a genetic test?
Genetic testing for the RET gene is worth considering if you or a close relative has medullary thyroid cancer, an inherited condition called MEN2, or an adrenal gland tumor called pheochromocytoma. A RET test can confirm an inherited cause and help guide screening and treatment for you and family members.
A genetic result is only one part of your health story
A genetic result can be informative, but how much it explains varies by the condition and the kind of variant involved. Lifestyle, environment, age, and medical history are among the many factors that shape how the body functions over time. For some conditions, especially those affected by many genes, genetic information offers context rather than certainty and is most useful when viewed alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas like medication response, genetic results can also help put individual experiences in context.
Pharmacogenetics
How variants shape your response to medicine
Changes in the RET gene in some thyroid and lung cancers can help identify people who may respond to targeted medicines such as selpercatinib or pralsetinib. This is different from genes that change how the liver breaks down a drug, because here the gene change is part of what the medicine is designed to block. More broadly, genetic variation can influence how well a treatment works or how sensitive someone is to side effects. That helps explain why the same medicine can have different results in different people.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect the way people respond to medications. It studies the relationship between genes and drugs to help explain why the same treatment can work differently from one person to another. For many medicines, genes influence how strongly a drug works or how the body handles it. This information can support treatment decisions that are both better informed and more individualized. To explore this subject further, you can learn more in the LearnHub.
Drugs influenced by the RET gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in routine prescribing, so questions about how a medicine may work for you, side effects, or drug interactions are best discussed with your doctor. RET is different in cancer care, where changes in the tumor can help guide targeted treatment choices for some thyroid and lung cancers.
History
The RET gene entered cancer research in the 1980s, when scientists identified it while studying DNA changes that could drive tumor growth. Its name came from that discovery process: “rearranged during transfection,” a lab method used at the time. Building on this early work, scientists uncovered more about the gene. In the early 1990s, inherited variants in the RET gene were linked to multiple endocrine neoplasia type 2, which gave families a clearer explanation for certain patterns of thyroid and hormone related tumors. Researchers later found that other RET gene variants were involved in Hirschsprung disease, showing that the same gene could be tied to very different conditions. This history made the RET gene an important part of both inherited cancer genetics and precision cancer care.