The most common non-VHL mutations in ccRCC can be grouped as chromatin modifiers located in the proximity of the VHL gene (BAP1, PBRM1, SETD2) or distally- (KDM6A, KDM5C, ARID1A, SMARCA4) and PI3K/AKT-related signaling modifiers. This evidence concerns the gene SETD2 and nonpapillary renal cell carcinoma.