Explore the disease pathogenesis

VHL disease is caused by the mutation of the VHL gene,
which leads to a functional loss of VHL protein.1

Many functions have been attributed to
the VHL protein. These are largely
divided into HIF-dependent or HIF-independent processes.1,2

HIF-dependent1–5

  • HIF-dependent processes are involved
    in oxygen sensing and adaptive
    response to hypoxia.
  • Dysregulation of these processes may result in angiogenesis, cellular proliferation and migration, and erythropoiesis, which are linked to tumorigenesis.

HIF-independent3,4

  • VHL protein regulates a number of HIF-independent processes, including regulation of extracellular matrix,
    primary cilium, mitosis, and DNA repair.
  • Dysregulation of these processes
    may contribute to development of
    cysts or dysplasia.
Due to the dysregulation of these processes, many patients with VHL disease present with cysts and tumors in multiple organs.1,3,4

VHL = von Hippel-Lindau; HIF = hypoxia-inducible factor; DNA = deoxyribonucleic acid.

See how VHL disease manifests in patients

References: 1. Varshney N, Kebede AA, Owusu-Dapaah H, et al. A review of von Hippel-Lindau syndrome. J Kidney Cancer VHL. 2017;4(3):20–29. 2. Maher ER, Sandford RN. von Hippel-Lindau disease: an update. Curr Genet Med Rep. 2019;7(4):227–235. 3. Jonasch E, Walker CL, Rathmell WK. Clear cell renal cell carcinoma ontogeny and mechanisms of lethality. Nat Rev Nephrol. 2021;17(4):245–261. 4. Hudler P, Urbancic M. The role of VHL in the development of von Hippel-Lindau disease and erythrocytosis. Genes (Basel). 2022;13(2):362. 5. Kaelin WG Jr. HIF2 inhibitor joins the kidney cancer armamentarium. Am J Clin Oncol. 2018;36(9):908–910.

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