TOP1 (DNA topoisomerase 1) variants and mutations

TOP1 (also known as DNA topoisomerase 1) is a human protein-coding gene encoding a DNA topoisomerase 1 protein. It relieves torsional strain in DNA by creating and resealing transient single-strand breaks during replication and transcription. Trapping of the cleavage intermediate is the mechanism exploited by topoisomerase I inhibitors such as irinotecan and topotecan in cancer therapy. This analysis covers 785 TOP1 variants and mutations. Of these, 54% have computational variant effect predictions. Disease context includes small cell lung carcinoma, breast cancer, and neoplasm. Example TOP1 variants include S2C, S2G, and S2I.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable TOP1 variants

Examples include S2C, S2G, S2I, S2N, S2R, S2S, G3R, G3W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.