Only a fraction of the >11 million missense variants identified in humans has a known clinical significance. Post-translational modifications (PTMs), such as phosphorylation, glycosylation and ubiquitination, are key regulators of protein function and structure. PTMs depend on correct protein folding and the recognition and binding of enzymes to specific amino acid motifs near modification sites. AlphaFold models provide an unprecedented opportunity to explore variants on 3D structures, enabling systematic identification of amino acid substitutions that could affect PTMs and should be further investigated experimentally.

We present Missense3D-PTMdb, a “one-stop-shop” interactive web tool that provides a user-friendly sequence-structure mapping of 20,235 human proteins, 11,5 million naturally occurring human missense variants, >60 PTM types and 203,775 PTM residues and their neighbours in sequence and 3D structure space using AlphaFold models of the human proteome. The resource also supports visualisation of novel variants not in the database. Missense3D-PTMdb is freely available at https://missense3d.bc.ic.ac.uk/ptmdb.