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Updated: Jul 6, 2025

A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
Missense3D-TM: Predicting the Effect of Missense Variants in Helical Transmembrane Protein Regions Using 3D Protein
Gordon Hanna1, Tarun Khanna1, Suhail A Islam1
1Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
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/.
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