Radusky, LeandroModenutti, CarlosDelgado Blanco, JavierBustamante, Juan P.Vishnopolska, SebastianKiel, ChristinaSerrano Pubull, Luis, 1982-Marti, MarceloTurjanski, Adrián2019-11-152019-11-152018Radusky L, Modenutti C, Delgado J, Bustamante JP, Vishnopolska S, Kiel C, Serrano L, Marti M, Turjanski A. VarQ: a tool for the structural and functional analysis of human protein variants. Front Genet. 2018; 9:620. DOI 10.3389/fgene.2018.006201664-8021http://hdl.handle.net/10230/42861Understanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Despite the existence of several bioinformatic algorithms and servers that predict if a SAS is pathogenic or not, they give little or no information at all on the reasons for pathogenicity prediction and on the actual predicted effect of the SAS on the protein function. Moreover, few actual methods take into account structural information when available for automated analysis. Moreover, many of these algorithms are able to predict an effect that no necessarily translates directly into pathogenicity. VarQ is a bioinformatic pipeline that incorporates structural information for the detailed analysis and prediction of SAS effect on protein function. It is an online tool which uses UniProt id and automatically analyzes known and user provided SAS for their effect on protein activity, folding, aggregation and protein interactions, among others. We show that structural information, when available, can improve the SAS pathogenicity diagnosis and more important explain its causes. We show that VarQ is able to correctly reproduce previous analysis of RASopathies related mutations, saving extensive and time consuming manual curation. VarQ assessment was performed over a set of previously manually curated RASopathies (diseases that affects the RAS/MAPK signaling pathway) related variants, showing its ability to correctly predict the phenotypic outcome and its underlying cause. This resource is available online at http://varq.qb.fcen.uba.ar/. Supporting Information & Tutorials may be found in the webpage of the tool.application/pdfeng© 2018 Radusky, Modenutti, Delgado, Bustamante, Vishnopolska, Kiel, Serrano, Marti and Turjanski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fgene.2018.00620Variation diagnosisBioinformaticsWeb serverSingle amino acid substitutionsSingle amino acid substitutions classificationFoldXinfo:eu-repo/semantics/openAccess