The VHL gene helps keep cell growth under control by helping cells respond properly to oxygen. This gene plays an important role in removing growth signals when they are no longer needed. If it does not work properly, cells may grow in a less controlled way, and cysts or tumors can form in places such as the kidneys, eyes, brain, adrenal glands, or inner ear. An inherited disease-causing variant in the VHL gene causes von Hippel-Lindau syndrome.
What is a gene?
Genes are sections of DNA that hold instructions your cells use to make molecules or manage processes in the body. Some genes carry the information needed to produce proteins, the parts of cells that do the work. Others mainly help decide when, where, and how strongly certain processes take place. Taken together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medications. For a deeper look at this topic, you can read more in the LearnHub.
Overview
VHLGene function
What if the gene works
The VHL gene helps cells respond to oxygen levels. Its protein helps control blood vessel growth and keeps cell growth more balanced.
Risk
What if the gene does not work
Variants in the VHL gene range from milder to more severe and can change which features appear. They can cause von Hippel-Lindau syndrome, linked to tumors and cysts, and some variants also cause excess red blood cells.
Treatment
What does that mean for your treatment
A confirmed pathogenic variant in the VHL gene can make belzutifan a treatment option for certain tumors linked to VHL, especially when surgery is not the best next step. This can shape whether care centers on surgery, close monitoring, or a targeted medicine instead of repeated procedures.
Conditions associated with VHL
Gene function
What if the gene works
Your cells are always adjusting to oxygen and everyday growth signals. The VHL gene helps keep these responses appropriately timed by marking certain proteins for removal when oxygen is normal. This is a key part of how cells respond to oxygen in the body.
The VHL gene helps cells tell when oxygen is normal. It marks proteins that trigger low oxygen responses for removal, so those signals switch off at the right time.
Inside your cells, the VHL gene is part of a system that labels selected proteins for disposal. This steady cleanup helps keep cell messaging organized and controlled.
By controlling oxygen related signals, the VHL gene helps guide blood vessel growth, red blood cell production, and energy use. This keeps normal body responses matched to changing needs.
What is a variant?
A genetic variant is a minor difference in the DNA sequence within a gene. These differences are common and help explain normal variation among people, including differences in appearance, metabolism, and the way the body reacts to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. Sometimes, though, a variant changes how a gene works more significantly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the VHL gene can change the shape, stability, or binding ability of the VHL protein, so cells may not clear hypoxia signaling proteins normally. This is one of the main ways VHL gene variants affect protein function inside the cell. Some missense variants leave partial activity, while more disruptive variants such as truncating changes or deletions often leave little or no working protein. That functional range can influence which VHL-related features appear and how early they begin.
How variants are linked to conditions
Pathogenic variants in the VHL gene cause von Hippel-Lindau disease, the main condition linked to variants in the VHL gene. This inherited condition raises the chance of hemangioblastomas, kidney cancer, pheochromocytoma, pancreatic neuroendocrine tumors, and some inner ear tumors. Some variants are more strongly associated with pheochromocytoma, while others are linked to a broader pattern of tumors within the same syndrome.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely found in the general population. Most do not have a direct effect on health and simply reflect natural human diversity. For many genes, having a variant associated with a condition indicates a possible link rather than a certain diagnosis, especially when multiple genes and environmental influences are involved. In some situations, though, a single 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 a disease-causing change in the VHL gene, risk is driven mainly by the variant itself, and the exact pattern can differ by the specific change in the gene. Age also matters, because VHL-related growths often appear over time. There is not enough evidence to say lifestyle changes lower the underlying VHL risk.
Inheritance of VHL variants
The inheritance pattern for VHL-related conditions can differ depending on the specific condition and variant. For von Hippel-Lindau disease, variants in the VHL gene are usually inherited in an autosomal dominant pattern, which means a parent carrying the variant has a 50% chance of passing it to each child; some people have a new, de novo variant that was not inherited from either parent. A different VHL-related condition, congenital erythrocytosis, follows an autosomal recessive pattern, so it usually appears only when a person inherits a VHL variant from both parents. This explains how VHL gene variants are inherited in families.
What does my VHL result mean for my family?
A harmful change in the VHL gene is usually passed down in families in a dominant way, so close relatives like parents, brothers, sisters, and children may also carry the same change and may want to consider genetic counseling and testing. Each child of someone with a disease-causing VHL variant has a 1 in 2 chance of inheriting it. Some people are the first in their family to have the variant, so a parent does not always have it.
Genetic information
Genetic testing
How you find out about variants
Testing for changes in the VHL gene usually uses a blood or saliva sample. A lab reads the gene’s DNA sequence and may also check for missing or extra pieces to look for a variant. VHL genetic testing can confirm an inherited VHL condition or show whether a known family variant was passed on.
When should I consider getting a genetic test?
Consider VHL genetic testing if you or close relatives have von Hippel-Lindau syndrome or a pattern of related tumors, especially tumors in the eye, brain or spinal cord, adrenal glands, kidneys, or pancreas at a young age. Testing can help confirm whether these growths are part of an inherited condition and guide family screening.
A genetic result is only one part of your health story
Genetic results can provide useful insight, although how much they reveal varies with the condition and the kind of variant present. Over time, the way the body functions is shaped by many factors, including lifestyle, environment, age, and medical history. With some conditions, particularly those affected by many genes, genetic information offers context rather than certainty and makes the most sense when considered together with other parts of care. In other situations, a genetic finding may give a clear answer. For topics like medication response, genetic results can also help put personal experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small differences in genes can change how the body breaks down a drug, moves it through the body, or responds to it at its target. This helps explain why the same medication may work well for one person, work less well for another, or cause more side effects in someone else. These differences are common and are one part of the bigger picture, along with age, other health conditions, and other medicines.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can shape a person’s response to medications. By looking at relationships between genes and drugs, it helps explain why treatments do not work the same way for everyone. For many medicines, genes affect both how strongly a drug works and how the body handles it. This information can support treatment decisions that are more informed and more individualized. More detail on this topic is available in the LearnHub.
Drugs influenced by the VHL gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding routine medication choices, so questions about side effects, new symptoms, or how your medicines fit your overall health are best discussed with your doctor. In people living with VHL-related tumors, the VHL gene can still matter in cancer care because it may help shape discussions about targeted treatment options with a specialist.
History
Families and communities once noticed patterns that seemed to pass from parent to child in what is now called von Hippel-Lindau disease. In the late 19th and early 20th centuries, doctors described unusual blood vessel tumors in the eye and brain, and later recognized that these findings could occur together in families. The condition was eventually named after Eugen von Hippel and Arvid Lindau, whose reports helped connect these features. Building on this early work, scientists mapped the responsible region to chromosome 3, and in 1993 the VHL gene was identified. That discovery became a landmark in cancer genetics. Research on the VHL gene later helped reveal how cells sense oxygen, a breakthrough that contributed to the 2019 Nobel Prize in Physiology or Medicine.