Motivated by the specific clinical need of biomarkers specific to rare subtypes of renal cell carcinoma, we carried out multi-omics analyses to identify protein/mRNA biomarkers to distinguish benign ROs from chRCC (MAPRE3, ADGRF5, GPNMB), pRCC from MTSCC (SOSTDC1, PIGR), and tumors with high wGII (PYCR1, IGF2BP3). Here, ADGRF5 is linked to hereditary clear cell renal cell carcinoma.