The RHBDF2 gene helps control how cells send growth and repair signals, especially in the skin and the lining of some organs. This gene plays an important role in helping cells release chemical messengers that guide healing and inflammation. Certain inherited variants that change how the RHBDF2 gene works can cause very thick skin on the palms and soles, called tylosis, and can raise the chance of esophageal cancer. Many other variants in the RHBDF2 gene have little or no effect on health.
What is a gene?
Genes are stretches of DNA that hold instructions your cells use to make molecules or direct processes in the body. Some genes provide the directions for making proteins, which are the working parts of cells. Other genes mainly regulate when certain processes happen, where they happen, and how strongly they run. Together, genes affect how the body develops and works, and they can also shape how you respond to food, stress, or medications. For a deeper look at this topic, you can find more in the LearnHub.
Overview
RHBDF2Gene function
What if the gene works
The RHBDF2 gene helps control signals at the cell surface. It supports the release of growth and immune messengers, helping with skin repair and normal tissue responses.
Risk
What if the gene does not work
Variants in the RHBDF2 gene are known for causing tylosis, with thickened skin on the palms and soles and a raised risk of esophageal cancer. Milder and more severe variants can influence when features appear and how marked they are.
Treatment
What does that mean for your treatment
No RHBDF2-specific treatment or drug choice is currently established for people with a pathogenic variant in the RHBDF2 gene. The RHBDF2 gene is being studied as a possible biomarker and drug target in some cancer and skin research.
Conditions associated with RHBDF2
Gene function
What if the gene works
Cell-to-cell messaging depends on well-timed protein release at the cell surface. The RHBDF2 gene supports that timing by helping ADAM17, a protein that releases certain cell signals, reach the right place and work properly. This is a central part of what the RHBDF2 gene does in the body.
Inside your cells, the RHBDF2 gene helps guide ADAM17 through the cell’s protein delivery pathway. This lets ADAM17 reach the cell surface, where many cell messages are released.
The RHBDF2 gene helps ADAM17 mature into a working form before it acts at the cell surface. This careful setup supports steady, controlled signaling.
Through ADAM17, the RHBDF2 gene supports the release of selected growth and immune signals from the cell surface. These signals help nearby cells coordinate repair, renewal, and routine responses.
What is a variant?
A genetic variant is a slight difference in the DNA sequence within a gene. These differences are common and help shape normal human diversity, including variation in appearance, metabolism, and how the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some situations, however, a variant can change how a gene works more substantially and may contribute to or lead to a genetic condition.
Genetic variants
What if the gene does not work
Most disease linked variants in the RHBDF2 gene make the iRhom2 protein too active, not missing. They can help ADAM17, a protein that releases growth signals from the cell surface, become more active than usual. This is a key part of how RHBDF2 gene variants affect protein function. Stronger activating variants may lead to earlier or more noticeable thickening of the palms and soles, while milder variants may have a smaller effect.
How variants are linked to conditions
Pathogenic variants in the RHBDF2 gene cause tylosis with esophageal cancer, also called Howel-Evans syndrome. This well-established RHBDF2 gene and esophageal cancer risk link is seen in families where affected relatives often develop thickened skin on the palms and soles and have a much higher chance of esophageal squamous cell carcinoma. The skin changes usually appear before the cancer risk becomes most relevant in adulthood.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely found across the general population. Most do not have a direct effect on health and instead reflect natural human diversity. For many genes, carrying a variant connected with a condition suggests a possible association rather than a definite diagnosis, especially when several genes and environmental factors are involved. There are also cases in which one specific, well-characterized variant in a particular gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For people with an inherited RHBDF2 change linked to tylosis, the gene itself is the main reason risk is high, especially for cancer of the food pipe (esophagus). Smoking and heavy alcohol use may add to that cancer risk, so avoiding these and keeping up with regular monitoring can help catch problems early.
Inheritance of RHBDF2 variants
RHBDF2-related conditions are inherited in an autosomal dominant pattern. In practical terms, this means a person with a disease-causing variant in the RHBDF2 gene can pass it to a son or daughter, and each child has a 50% chance of inheriting that variant. This is the main answer to how RHBDF2 variants are inherited, especially for the well-known inherited skin condition linked to a higher risk of esophageal cancer in some families. A parent of any sex can pass the variant on, and sons and daughters can inherit it equally.
What does my RHBDF2 result mean for my family?
A disease-causing change in the RHBDF2 gene is usually passed down in families in a dominant pattern, so close relatives such as parents, brothers, sisters, and children may also carry the same change. In practical terms, this can mean skin changes on the hands and feet in several family members, along with a higher chance of esophageal cancer in relatives who carry it. Family implications can be important across generations.
Genetic information
Genetic testing
How you find out about variants
To find out whether you carry a variant in the RHBDF2 gene, a lab can analyze DNA from a blood sample, saliva sample, or cheek swab. Genetic testing for RHBDF2 variants reads the gene’s sequence and compares it with the usual pattern to identify changes that may help explain a diagnosed condition or confirm a suspected one.
When should I consider getting a genetic test?
Genetic testing for the RHBDF2 gene may be worth considering if thickened skin on the palms and soles runs in your family, especially alongside a family history of esophageal cancer. In some families, a harmful RHBDF2 change can confirm an inherited condition linked to both skin changes and a high cancer risk.
A genetic result is only one part of your health story
A genetic result can provide useful insight, but how much it explains depends on the condition and on the type of variant involved. How the body works over time is also shaped by many other factors, including lifestyle, environment, age, and medical history. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is best 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
Genetic variation can affect how people respond to medicines. This helps explain why the same treatment may work well for one person, have less effect in another, or cause more side effects in someone else. Differences in how the body absorbs, breaks down, transports, or responds to a drug are common, and they can influence both benefit and sensitivity.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can affect a person’s response to medications. It looks at gene and drug patterns to better explain why the same treatment may work differently from one person to another. For many medicines, genes help shape how strongly a drug works or how the body processes it. This information can support more informed and more individualized treatment decisions. More detailed information on this topic is available in the LearnHub.
Drugs influenced by the RHBDF2 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting how medicines will work, so any concerns about side effects, new symptoms, or how a treatment is affecting you are best discussed with your doctor.
History
The RHBDF2 gene entered medical genetics through studies of families with an inherited skin condition called tylosis, which can occur alongside a higher chance of esophageal cancer. In the early 2010s, researchers identified harmful variants in the RHBDF2 gene as the cause in well known affected families from the United Kingdom. Before that, the gene had been grouped with rhomboid related genes, but its medical importance was not yet clear. Over time, scientists’ understanding of the gene’s role changed as genetic studies connected it to this distinctive inherited pattern. These findings helped clarify a long-standing family cancer syndrome and gave affected relatives a more precise genetic explanation. Since then, RHBDF2 has remained a specialized but important part of inherited cancer research.