PolED: a manually curated database of functional studies of POLE and POLD1 variants reported in humans

Human POLE and POLD1 genes encode DNA polymerases responsible for genome replication and proofreading of DNA synthesis errors. Germline and somatic POLE/POLD1 mutations compromising the polymerase fidelity cause cancers with high mutational burden. Ultramutation is associated with a better prognosis and immunotherapy response, highlighting the need to define tumour POLE/POLD1 status unambiguously. Prior studies assessed the functional significance of numerous POLE/POLD1 variants in experimental models. However, the data remain scattered and difficult to evaluate by non-specialists, limiting their utility for research and clinical applications. Through manual literature curation, we integrated data from functional studies of clinically relevant POLE and POLD1 variants into PolED, a publicly available database (https://poled-db.org). PolED compiles information on variant effects in biochemical assays, yeast, mammalian cells, and mouse tumour models along with supporting references. It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.