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-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.
- VHL protein regulates a number of HIF-independent processes, including regulation of extracellular
primary cilium, mitosis, and DNA repair.
- Dysregulation of these processes
may contribute to development of
cysts or dysplasia.
It is believed that the aforementioned processes are the reason many patients with VHL disease may
present with cysts and tumors in multiple organs.1