Importantly, genetic polymorphism at the 11q13.3 locus, which causes predisposition to RCC development, affects HIF-2α dependent induction of CCND1 expression by allowing HIF-2α to bind to the enhancer region of Cyclin D1, a phenomenon specifically restricted to VHL-deficient RCC [130]. The gene discussed is CCND1; the disease is renal cell carcinoma.