Functionally, UBE2S knockdown suppressed ccRCC cell proliferation and migration, while immune correlation analyses linked UBE2S to altered tumor immunogenicity and genomic stability.<h4>Conclusions</h4>Our study identifies NK cell subsets and UBE2S as key contributors to ccRCC progression and establishes a clinically relevant 12-gene prognostic model, offering potential targets for precision therapy. Here, UBE2S is linked to neoplasm.