VHL R167Q (c.500G>003eA)

R167Q是遗传性von hippel-lindau（vhl）病最常见的点突变，破坏了与拉长素c结合的vhl基因，降低了vhl拉长素b-拉长素c（vbc）e3连接酶复合物的水平，抑制了vhl调节hif2α的能力。这种部分功能反过来导致肿瘤发生的风险增加。然而，VHL衍生的透明细胞肾细胞癌模型显示，蛋白酶体抑制剂硼替佐米和卡非佐米可以稳定突变的VHL-R167Q，导致HIF2α下调，抑制肿瘤发生。
R167Q is the most common point mutation in hereditary Von Hippel-Lindau (VHL) disease and disrupts the VHL genes binding to elongin C reducing the levels of the VHL-elongin B-elongin C (VBC) E3 ligase complex and inhibiting the ability of VHL to regulate HIF2α. This partial function in turn leads to an increased risk of tumorgenesis. VHL derived clear cell renal cell carcinoma models however have shown the proteasome inhibitors bortezomib and carfilzomib can act to stabilize mutant VHL-R167Q leading to downregulation of HIF2α and suprressed tumorgenesis.