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Also known asHRCA1, RCA1, VHL1, pVHL
VHL (von Hippel-Lindau) is a gene that encodes the von Hippel-Lindau protein (VHL), which is a tumor suppressor. The VHL protein plays a critical role in the regulation of cell growth and division by targeting and degrading a transcription factor called hypoxia-inducible factor (HIF) which is involved in the response of cells to low oxygen levels.
Mutations in the VHL gene have been associated with von Hippel-Lindau disease (VHL), an inherited disorder characterized by the development of benign and malignant tumors in different parts of the body such as the retina, brain, spinal cord, kidney and adrenal glands. VHL is an autosomal dominant disorder, meaning that an individual with one copy of the mutant gene will develop the disorder.
In normal cells, the VHL protein binds to HIF, tagging it for degradation and preventing it from activating genes that promote cell growth and survival under low oxygen conditions. However, in VHL disease, the VHL protein is non-functional due to genetic mutations, leading to the accumulation of HIF and activation of HIF-responsive genes, which leads to the development of tumors in different parts of the body.
VHL disease is rare, but VHL mutations are also found in several types of cancer, particularly clear cell renal cell carcinoma(ccRCC), which is the most common type of kidney cancer and also seen in other type of cancer such as pheochromocytoma and hemangioblastoma.