VHL von Hippel-Lindau tumor suppressor
Also known as: pVHL, VHL1, VHL_HUMAN.
Approximate pronunciation (generated from the name, not a recording):
- VHL vee-aitch-el
- von Hippel-Lindau tumor suppressor von hippel lindau tumor suppressor
What this gene does
The VHL gene provides instructions for making a protein that functions as part of a complex (a group of proteins that work together) called the VCB-CUL2 complex. This complex targets other proteins to be broken down (degraded) by the cell when they are no longer needed. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells.
One of the targets of the VCB-CUL2 complex is a protein called hypoxia-inducible factor 2-alpha (HIF-2α). HIF-2α is one part (subunit) of a larger protein complex called HIF, which plays a critical role in the body's ability to adapt to changing oxygen levels. HIF controls several genes involved in cell division, the formation of new blood vessels, and the production of red blood cells. It is the major regulator of a hormone called erythropoietin, which controls red blood cell production. HIF's function is particularly important when oxygen levels are lower than normal (hypoxia). However, when adequate oxygen is available, the VCB-CUL2 complex keeps HIF from building up inappropriately in cells.
The VHL protein likely plays a role in other cellular functions, including the regulation of other genes and control of cell division. Based on this function, the VHL protein is classified as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The VHL protein is also involved in the formation of the extracellular matrix, which is an intricate lattice that forms in the spaces between cells and provides structural support to tissues.
Source: MedlinePlus Genetics (reviewed 2012-08; source updated 2023-05-08).
Von Hippel-Lindau syndrome
Approximate pronunciation (generated from the name, not a recording):
- Von Hippel-Lindau syndrome von hippel lindau syndrome
Also known as: Angiomatosis retinae, Cerebelloretinal angiomatosis, familial, Hippel-Lindau disease, VHL syndrome, Von Hippel-Lindau disease.
What is Von Hippel-Lindau syndrome?
Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life.
Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss.
People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.
Von Hippel-Lindau syndrome is associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands (small hormone-producing glands located on top of each kidney). Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromocytomas are particularly dangerous in times of stress or trauma, such as when undergoing surgery or in an accident, or during pregnancy.
About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness.
Noncancerous tumors may also develop in the liver and lungs in people with von Hippel-Lindau syndrome. These tumors do not appear to cause any signs or symptoms.
Source: MedlinePlus Genetics (reviewed 2008-07; source updated 2020-08-18).
How it is inherited
Mutations in the VHL gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and cysts. Most people with von Hippel-Lindau syndrome inherit an altered copy of the gene from an affected parent. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or very early in development.
Unlike most autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the VHL gene must be altered to trigger tumor and cyst formation in von Hippel-Lindau syndrome. A mutation in the second copy of the VHL gene occurs during a person's lifetime in certain cells within organs such as the brain, retina, and kidneys. Cells with two altered copies of this gene do not make functional VHL protein, which allows tumors and cysts to develop. Almost everyone who inherits one VHL mutation will eventually acquire a mutation in the second copy of the gene in some cells, leading to the features of von Hippel-Lindau syndrome.
Source: MedlinePlus Genetics (reviewed 2008-07; source updated 2020-08-18).
How common it is
MedlinePlus Genetics Frequency
The incidence of von Hippel-Lindau syndrome is estimated to be 1 in 36,000 individuals.
Source: MedlinePlus Genetics (reviewed 2008-07; source updated 2020-08-18).
Research studies
17 studies recruiting people with Von Hippel-Lindau syndrome. Showing the first 5 of 17.
- National Eye Institute Biorepository for Retinal Diseases (NCT01496625)
- A Study of HS-10516 in Patients With VHL Syndrome Associated Tumors (NCT06553339)
- Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients (NCT06523582)
- MyVHL: Patient Natural History Study (NCT03749980)
- Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors (NCT04074135)
See all recruiting studies on ClinicalTrials.gov.
Source: ClinicalTrials.gov (retrieved 2026-10-04).
Family and care
What a diagnosis can mean for a family, and what to ask. This guidance is general, not specific to one gene.
What is a genetic consultation?
A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic conditions. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition.
Genetics professionals include medical geneticists (doctors who specialize in genetics) and genetic counselors (certified healthcare workers with experience in medical genetics and counseling). Other healthcare professionals such as nurses, psychologists, and social workers trained in genetics can also provide genetic consultations.
Consultations usually take place in a doctor’s office, hospital, genetics center, or other type of medical center. These meetings are most often in-person visits with individuals or families, but they are occasionally conducted in a group. Additionally, genetic consultations may be carried out using telemedicine (also known as telehealth), in which the meeting is done from a distance using computers, cameras, videoconferencing tools, or the telephone.
Source: MedlinePlus Genetics.
Why might someone have a genetic consultation?
Individuals or families who are concerned about an inherited condition may benefit from a genetic consultation. The reasons that a person might be referred to a genetic counselor, medical geneticist, or other genetics professional include:
A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer.
Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
A child with a known inherited disorder, a birth defect, intellectual disability, or developmental delay.
A woman who is pregnant or plans to become pregnant at or after age 35. (Some chromosomal disorders occur more frequently in children born to older women.)
Abnormal test results that suggest a genetic or chromosomal condition.
An increased risk of developing or passing on a particular genetic disorder on the basis of a person’s ethnic background.
People related by blood (for example, cousins) who plan to have children together. (A child whose parents are related may be at an increased risk of inheriting certain genetic disorders.)
A person received results from direct-to-consumer genetic testing and they want to discuss the implications of the results.
A genetic consultation is also an important part of the decision-making process for genetic testing. A visit with a genetics professional may be helpful even if testing is not available for a specific condition, however.
Source: MedlinePlus Genetics.
What happens during a genetic consultation?
A genetic consultation provides information, offers support, and addresses a patient’s specific questions and concerns. To help determine whether a condition has a genetic component, a genetics professional asks about a person’s medical history and takes a detailed family health history (a record of health information about a person's immediate and extended family). The genetics professional may also perform a physical examination and recommend appropriate medical tests.
If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment.
During a consultation, a genetics professional will:
Interpret and communicate complex medical information.
Help each person make informed, independent decisions about their health care and reproductive options.
Respect each person’s individual beliefs, traditions, and feelings.
A genetics professional will NOT:
Tell a person which decision to make.
Coerce a couple about whether or not to have children.
Recommend that a woman continue or end a pregnancy.
Tell someone whether to undergo testing for a genetic disorder.
Source: MedlinePlus Genetics.
What is genetic counseling?
The goal of genetic counseling is to help you learn more about the causes of genetic conditions and how they affect you.
Genetic counselors can: Review your family and medical histories; Explain how genetic conditions are passed down through families; Figure out if you or your family members are at risk for disease; Find and give you information about genetic conditions; Offer guidance to help you make informed choices or life plans; Provide information about testing options and help you decide what is best for you and your family; Help you find referrals to medical specialists, advocacy and support networks, and other resources.
Source: National Society of Genetic Counselors and Genetic Alliance (CC BY; published 2008).
Where to go next
- Von Hippel-Lindau syndrome: VHL Alliance — The patient advocacy organization for Von Hippel-Lindau syndrome.
- Find a Genetic Counselor (NSGC) — Find a genetic counselor near you.
- Search ClinicalTrials.gov for Von Hippel-Lindau syndrome — Look for studies that are recruiting people with Von Hippel-Lindau syndrome.
Words you may meet
Some technical words appear in the sections above and in the details below. Here is what they mean, in words from a public genetics glossary.
- Gene
- The gene is considered the basic unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify physical and biological traits. Most genes code for specific proteins, or segments of proteins, which have differing functions within the body. Humans have approximately 20,000 protein-coding genes. NHGRI Talking Glossary of Genomic and Genetic Terms
- Chromosome
- Chromosomes are threadlike structures made of protein and a single molecule of DNA that serve to carry the genomic information from cell to cell. In plants and animals (including humans), chromosomes reside in the nucleus of cells. Humans have 22 pairs of numbered chromosomes (autosomes) and one pair of sex chromosomes (XX or XY), for a total of 46. Each pair contains two chromosomes, one coming from each parent, which means that children inherit half of their chromosomes from their mother and half from their father. Chromosomes can be seen through a microscope when the nucleus dissolves during cell division. NHGRI Talking Glossary of Genomic and Genetic Terms
- Autosomal Recessive Disorder
- Autosomal recessive is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Recessive” means that two copies of the mutated gene (one from each parent) are required to cause the disorder. In a family where both parents are carriers and do not have the disease, roughly a quarter of their children will inherit two disease-causing alleles and have the disease. By contrast, an autosomal dominant disorder requires only a single copy of the mutated gene from one parent to cause the disorder. Sickle cell anemia is an example of an autosomal recessive genetic disorder. NHGRI Talking Glossary of Genomic and Genetic Terms
- Autosomal Dominant Disorder
- Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the mutated gene (from one parent) is enough to cause the disorder. A child of a person affected by an autosomal dominant condition has a 50% chance of being affected by that condition via inheritance of a dominant allele. By contrast, an autosomal recessive disorder requires two copies of the mutated gene (one from each parent) to cause the disorder. Huntington’s disease is an example of an autosomal dominant genetic disorder. NHGRI Talking Glossary of Genomic and Genetic Terms
- Mitochondrial DNA
- Mitochondrial DNA is the circular chromosome found inside the cellular organelles called mitochondria. Located in the cytoplasm, mitochondria are the site of the cell’s energy production and other metabolic functions. Offspring inherit mitochondria — and as a result mitochondrial DNA — from their mother. NHGRI Talking Glossary of Genomic and Genetic Terms
- Genetic Imprinting
- Genomic imprinting is the process by which only one copy of a gene in an individual (either from their mother or their father) is expressed, while the other copy is suppressed. Unlike genomic mutations that can affect the ability of inherited genes to be expressed, genomic imprinting does not affect the DNA sequence itself. Instead, gene expression is silenced by the epigenetic addition of chemical tags to the DNA during egg or sperm formation. Epigenetic tags on imprinted genes usually stay in place for the life of the individual. NHGRI Talking Glossary of Genomic and Genetic Terms
- Protein
- Proteins are large, complex molecules that play many important roles in the body. They are critical to most of the work done by cells and are required for the structure, function and regulation of the body’s tissues and organs. A protein is made up of one or more long, folded chains of amino acids (each called a polypeptide), whose sequences are determined by the DNA sequence of the protein-encoding gene. NHGRI Talking Glossary of Genomic and Genetic Terms
- Mutation
- A mutation is a change in the DNA sequence of an organism. Mutations can result from errors in DNA replication during cell division, exposure to mutagens or a viral infection. Germline mutations (that occur in eggs and sperm) can be passed on to offspring, while somatic mutations (that occur in body cells) are not passed on. NHGRI Talking Glossary of Genomic and Genetic Terms
- Pathogenic Variant
- A pathogenic variant is a genomic variant that may increase a person’s risk of developing a condition, disorder or disease. In many cases, carrying a pathogenic variant does not guarantee that a person will develop the specific condition but increases the risk for it. Pathogenic variants can be inherited from a parent or can occur spontaneously due to factors such as environmental exposure and aging. NHGRI Talking Glossary of Genomic and Genetic Terms
- Genetic Testing
- Genetic testing is the use of a laboratory test to examine an individual’s DNA for variations, typically performed in the context of medical care, ancestry studies or forensics. In a medical setting, the results of a genetic test can be used to confirm or rule out a suspected genetic disease. Results may also be used to determine the likelihood of parents passing on a genetic mutation to their offspring. Genetic testing may be performed prenatally or after birth. Genetic testing is also used to study the genomes of tumors in cancer cases. NHGRI Talking Glossary of Genomic and Genetic Terms
- Carrier
- A carrier, as related to genetics, is an individual who “carries” and can pass on to its offspring a genomic variant (allele) associated with a disease (or trait) that is inherited in an autosomal recessive or sex-linked manner, and who does not show symptoms of that disease (or features of that trait). The carrier has inherited the variant allele from one parent and a normal allele from the other parent. Any offspring of carriers is at risk of inheriting a variant allele from their parents, which would result in that child having the disease (or trait). NHGRI Talking Glossary of Genomic and Genetic Terms
- Allele
- An allele is one of two or more versions of DNA sequence (a single base or a segment of bases) at a given genomic location. An individual inherits two alleles, one from each parent, for any given genomic location where such variation exists. If the two alleles are the same, the individual is homozygous for that allele. If the alleles are different, the individual is heterozygous. NHGRI Talking Glossary of Genomic and Genetic Terms
- Mendelian Inheritance
- Mendelian inheritance refers to certain patterns of how traits are passed from parents to offspring. These general patterns were established by the Austrian monk Gregor Mendel, who performed thousands of experiments with pea plants in the 19th century. Mendel’s discoveries of how traits (such as color and shape) are passed down from one generation to the next introduced the concept of dominant and recessive modes of inheritance. NHGRI Talking Glossary of Genomic and Genetic Terms
Details you may see on a test report
These names and numbers are the technical ones doctors and labs use. You do not need to memorize them.
Location
This is where the gene sits on its chromosome, so you can match it to coordinates on a test report.
3p25.3 · GRCh38 chr3:10,141,764–10,153,676
Open in Ensembl (primary) or UCSC Genome Browser (secondary).
Source: HGNC (HGNC:12687).
Recommended transcript
This is the reference transcript labs use when they report a change in this gene.
- MANE Select
NM_000551.4(RefSeq) /ENST00000256474.3(Ensembl)
Source: NCBI MANE.
Protein domains
These are the working parts of the protein, with the amino-acid positions each one covers.
- von Hippel-Lindau disease tumour suppressor, beta/alpha domain — amino acids 64–203
- von Hippel-Lindau disease tumour suppressor, alpha domain — amino acids 156–204
- von Hippel-Lindau disease tumour suppressor, beta domain — amino acids 63–144
Protein structure
This lets you look at the protein's 3D shape if you want to.
View the predicted structure in AlphaFold, or search the PDB for solved structures.
Source: UniProt (P40337).
Reported gene variants
ClinVar collects gene variants people have reported; it is a place to search, not a list on this page.
This page does not list individual variants. Search ClinVar for VHL instead.
Source: ClinVar.
What this page is not
This page is for education only. It is not medical advice, and it is not a diagnosis or a treatment plan. Talk with a doctor or a genetic counselor about your family's situation.