Even though a small fraction of clear cell renal cell carcinoma (3%) cases harboured inactivating mutations in SETD2 or JARID1C, these mutations are potentially of high relevance in hypoxia since 88% of samples with SETD2 and JARID1C inactivating mutations also harboured mutations in VHL and/or over-expression of egl nine homolog 3 (ELGN3) which is also known as HIF-prolyl hydroxylase 3 (PHD3) [43]. Here, VHL is linked to clear cell renal carcinoma.