WNK4 and hypertensive disorder: CUL3 mutations cause the most severe form of FHHt, with earlier onset of hypertension than is seen with WNK1, WNK4, or KLHL3 mutations.3,46 This is likely due to an important role for CUL3 in controlling vascular tone, a function dysregulated when mutant CUL3 is expressed.47,48