Mechanisms were explored via promoter analysis, cGAMP measurement, flow cytometry, cytokine profiling, and <i>in vivo</i> neutralization with STING- or interferon-α/β receptor-1 (IFNAR1) blocking antibodies.<h4>Results</h4>ENPP3 is hypoxia-inducible via HIF-1α, upregulated in ccRCC, and predicts poor prognosis. The gene discussed is HIF1A; the disease is nonpapillary renal cell carcinoma.