von Hippel Lindau (VHL)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 30 October 2015, last major update June 2005
Copyright: (c) 2003-2015,, Inc.
Table of Contents
Definition / General
Definition / General
  • Tumor suppressor gene (autosomal dominant) at 3p25-26, with 3 regions (A, B, C)
  • Familial cases of von Hippel Lindau syndrome are associated with translocations of this gene
  • Gene is inactivated by hypermethylation of CpG island in 5' region causing lack of expression of VHL or by mutation in binding region
  • Wild type protein competes with A subunit for binding to B/C complex; active mutation occurs in homologous sequence region
  • Mutated protein does not bind to elongin B and C subunits, which allows subunit A to bind, and increases rate of elongation through suppression of RNA polymerase pausing
  • Abnormalities associated with renal cell carcinoma, clear cell type