To test speckle targeting functions of HIF-2α, we utilized 786-O ccRCC cells, a patient-derived cell line that has elevated endogenous HIF-2α32, and inhibited the interaction between HIF-2α and its obligate DNA-binding heterodimer ARNT/HIF-1β with the PT2399 small molecule33,34. Here, ARNT is linked to nonpapillary renal cell carcinoma.