Both increased L-2HG and L2HGDH knockdown led to diminished 5-hmC level, which is strongly associated with tumor aggressiveness and an unfavorable prognosis, and restoring the activity of TET2 leads to inhibition of ccRCC growth both in vitro and in vivo (Shim et al., 2014; Shenoy et al., 2019). The gene discussed is L2HGDH; the disease is nonpapillary renal cell carcinoma.