Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types-to 'map' variants onto protein structures, to better understand how the variation causes disease, and thereby design therapeutics. Here we present the Genomics 2 Proteins portal ( https://g2p.broadinstitute.org/ ): a human proteome-wide resource that maps 20,076,998 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the Genomics 2 Proteins portal allows users to interactively upload protein residue-wise annotations (for example, variants and scores) as well as the protein structure beyond databases to establish the connection between genomics to proteins. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotypes.

Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA

Bioinformatics Division The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia

Cancer Data Sciences Dana Farber Harvard Cancer Center Boston MA USA

Center for the Development of Therapeutics Broad Institute of MIT and Harvard Cambridge MA USA

Department of Medical Biology University of Melbourne Parkville Victoria Australia

Department of Software Engineering Faculty of Mathematics and Physics Charles University Prague Czech Republic

Luxembourg Centre for Systems Biomedicine University of Luxembourg Esch sur Alzette Luxembourg

PATTERN Broad Institute of MIT and Harvard Cambridge MA USA

Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA

The Steve and Cindy Rasmussen Institute for Genomic Medicine Nationwide Children's Hospital Columbus OH USA

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bioRxiv. 2024 Jan 02:2024.01.02.573913. doi: 10.1101/2024.01.02.573913. PubMed

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