GENE REFERENCE / HGNC:12687

VHL

von Hippel-Lindau tumor suppressor

protein-coding gene3p25.3Gene information

What does this gene do?

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, National Library of Medicine. Source publication: 2023-05-08. Source review: 2012-08.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
von Hippel-Lindau diseaseMONDO:0008667 · Evaluated 2020-05-14	Autosomal dominant	DefinitiveHereditary Cancer Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 2,274
Submissions for variants in or overlapping this gene: 5,235
Submissions explicitly reporting this gene: 5,152
Alleles reported pathogenic / likely pathogenic: 482
VariationIDs with uncertain significance: 873
VariationIDs with conflicting classifications: 263

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about VHL?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 482 alleles in VHL reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in VHL.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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