{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hanna G"],"funding":["Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["168374"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617522"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["436(2)"],"pubmed_abstract":["Variant effect predictors assess if a substitution is pathogenic or benign. Most predictors, including those that are structure-based, are designed for globular proteins in aqueous environments and do not consider that the variant residue is located within the membrane. We report Missense3D-TM that provides a structure-based assessment of the impact of a missense variant located within a membrane. On a dataset of 2,078 pathogenic and 1,060 benign variants, spanning 711 proteins from 706 structures, Missense3D-TM achieved an accuracy of 66%, Mathews correlation coefficient of 0.37, sensitivity of 58% and specificity of 81%. Missense3D-TM performed similarly to mCSM-membrane: accuracy 66% vs 61% (p = 0.02) on an unbalanced test set and 70% vs 67% (p = 0.20) on a balanced test set. The Missense3D-TM website provides an analysis of the structural effects of the variant along with its predicted position within the membrane. The web server is available at http://missense3d.bc.ic.ac.uk/."],"journal":["Journal of molecular biology"],"pubmed_title":["Missense3D-TM: Predicting the Effect of Missense Variants in Helical Transmembrane Protein Regions Using 3D Protein Structures."],"pmcid":["PMC7617522"],"funding_grant_id":["BB/T010487/1","218242","BB/P023959/1","BB/X01830X/1","218242/Z/19/Z","104955","104955/Z/14/Z"],"pubmed_authors":["Khanna T","Islam SA","Hanna G","David A","Sternberg MJE"],"additional_accession":[]},"is_claimable":false,"name":"Missense3D-TM: Predicting the Effect of Missense Variants in Helical Transmembrane Protein Regions Using 3D Protein Structures.","description":"Variant effect predictors assess if a substitution is pathogenic or benign. Most predictors, including those that are structure-based, are designed for globular proteins in aqueous environments and do not consider that the variant residue is located within the membrane. We report Missense3D-TM that provides a structure-based assessment of the impact of a missense variant located within a membrane. On a dataset of 2,078 pathogenic and 1,060 benign variants, spanning 711 proteins from 706 structures, Missense3D-TM achieved an accuracy of 66%, Mathews correlation coefficient of 0.37, sensitivity of 58% and specificity of 81%. Missense3D-TM performed similarly to mCSM-membrane: accuracy 66% vs 61% (p = 0.02) on an unbalanced test set and 70% vs 67% (p = 0.20) on a balanced test set. The Missense3D-TM website provides an analysis of the structural effects of the variant along with its predicted position within the membrane. The web server is available at http://missense3d.bc.ic.ac.uk/.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2026-06-02T07:22:44.203Z","creation":"2025-07-05T03:04:13.424Z"},"accession":"S-EPMC7617522","cross_references":{"pubmed":["38182301"],"doi":["10.1016/j.jmb.2023.168374"]}}