Likewise, the overexpression of endogenous MISTRH correlating with loss of MISTR1 (NDUFA4) protein (Fig 6D) had been observed in clear cell Renal Cell Carcinoma (ccRCC) tumor samples and ccRCC cell lines [73], a disease characterized by hyperactive HIF signaling [47], but up-regulation of MISTRAV and the requirement of HIF in the regulation of this newly proposed circuit had not been tested (Fig 6D). The gene discussed is COXFA4L2; the disease is nonpapillary renal cell carcinoma.