SNPs 5-kb centromeric to rs7105934 modulate the binding and function of HIF-2α at the enhancer for CCND1. The minor (RCC-protective) allele at 11q13.3 disrupts HIF binding, DNA accessibility and interaction with the transcriptional apparatus at the CCND1 enhancer, and alters the allelic balance of CCND1 gene expression (21). Here, EPAS1 is linked to renal cell carcinoma.