Here, we profiled genomic binding of the NONO-TFE3 and PRCC-TFE3 fusions revealing their broad binding over the genome with more than 12,000 M/E-box-containing sites occupied in all 4 tRCC lines, of which 3900 were located in proximal promoters of genes associated with functions previously found to be regulated by native TFE3, such as lysosome and mTOR pathway, but also novel pathways pertinent to oncogenic transformation such as cell cycle, metabolism and ferroptosis. This evidence concerns the gene TFE3 and renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.