Functional and Structural Features of Disease-Related Protein Variants

Modern sequencing technologies provide an unprecedented amount of data of single-nucleotide variations occurring in coding regions and leading to changes in the expressed protein sequences. A significant fraction of these single-residue variations is linked to disease onset and collected in public databases. In recent years, many scientific studies have been focusing on the dissection of salient features of disease-related variations from different perspectives. In this work, we complement previous analyses by updating a dataset of disease-related variations occurring in proteins with 3D structure. Within this dataset, we describe functional and structural features that can be of interest for characterizing disease-related variations, including major chemico-physical properties, the strength of association to disease of variation types, their effect on protein stability, their location on the protein structure, and their distribution in Pfam structural/functional protein models. Our results support previous findings obtained in different data sets and introduce Pfam models as possible fingerprints of patterns of disease related single-nucleotide variations.