PHA II causing mutations in KLHL3 decreases Wnk4 binding to Cul3-RING ubiquitin ligase, decreasing WNK4 degradation and increasing its levels resulting in hypertension (Mori et al., 2013; Wakabayashi et al., 2013; Wu and Peng, 2013; Susa et al., 2014). This evidence concerns the gene CUL3 and Hypertension.