Moreover, in clear cell renal carcinoma (ccRCC) model of ccRCC expressing CD133 (ccRR-CD133+CSC), binding of TNF-α and/or R2TNF (a TNFR2 selective mutein agonist) to TNFR2 significantly phosphorylated VEGFR2, PI3K, Akt, and mTORC at amino acids Y1059, Thr308, Ser2448, and p110β respectively. The gene discussed is TNFRSF1B; the disease is clear cell renal carcinoma.