HHLA2 and nonpapillary renal cell carcinoma: We also generated a mutated METTL3 (W397A) construct with disordered enzymatic activity as described previously [16] and found that mutant METTL3 failed to elevate the m6A methylation level of HHLA2 mRNA in ccRCC cells (P < 0.01 in 786-O and P < 0.001 in ACHN, Fig. 3C).