ArticleProceedings of the National Academy of Sciences of the United States of America2019
Functional characterization of 3D protein structures informed by human genetic diversity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Predicted protein 3D structures provide essential insights into the genetic architecture underlying phenotypic diversity in maize.Genome research · 2026Article
- Proteome-wide assessment of differential missense variant clustering in neurodevelopmental disorders and cancer.Cell genomics · 2025Article
- Genomics 2 Proteins portal: a resource and discovery tool for linking genetic screening outputs to protein sequences and structures.Nature methods · 2024Article
- Prediction of cancer driver genes and mutations: the potential of integrative computational frameworks.Briefings in bioinformatics · 2024Review
- Estimating clinical risk in gene regions from population sequencing cohort data.American journal of human genetics · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.medRxiv : the preprint server for health sciences · 2023Article
- Faltwerk: a library for spatial exploratory data analysis of protein structures.Bioinformatics advances · 2023Article
- Predicting functional effect of missense variants using graph attention neural networks.Nature machine intelligence · 2022Article
- The 3D mutational constraint on amino acid sites in the human proteome.Nature communications · 2022Article
- PDAUG: a Galaxy based toolset for peptide library analysis, visualization, and machine learning modeling.BMC bioinformatics · 2022Article
- Missense Variants Reveal Functional Insights Into the Human ARID Family of Gene Regulators.Journal of molecular biology · 2022Article
- Characterization of intrinsically disordered regions in proteins informed by human genetic diversity.PLoS computational biology · 2022Article
- SWAAT Bioinformatics Workflow for Protein Structure-Based Annotation of ADME Gene Variants.Journal of personalized medicine · 2022Article
- VARIDT 2.0: structural variability of drug transporter.Nucleic acids research · 2022Article
- Self-assembled peptide and protein nanostructures for anti-cancer therapy: Targeted delivery, stimuli-responsive devices and immunotherapy.Nano today · 2021Article
- Performance Assessment of the Network Reconstruction Approaches on Various Interactomes.Frontiers in molecular biosciences · 2021Article
- Protein conformational switch discerned via network centrality properties.Computational and structural biotechnology journal · 2021Article
- Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Advances in Genomics for Drug Development.Genes · 2020Review
- MISCAST: MIssense variant to protein StruCture Analysis web SuiTe.Nucleic acids research · 2020Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Sequence variation data of the human proteome can be used to analyze 3D protein structures to derive functional insights. We used genetic variant data from nearly 140,000 individuals to analyze 3D positional conservation in 4,715 proteins and 3,951 homology models using 860,292 missense and 465,886 synonymous variants. Sixty percent of protein structures harbor at least one intolerant 3D site as defined by significant depletion of observed over expected missense variation. Structural intolerance data correlated with deep mutational scanning functional readouts for PPARG, MAPK1/ERK2, UBE2I, SUMO1, PTEN, CALM1, CALM2, and TPK1 and with shallow mutagenesis data for 1,026 proteins. The 3D structural intolerance analysis revealed different features for ligand binding pockets and orthosteric and allosteric sites. Large-scale data on human genetic variation support a definition of functional 3D sites proteome-wide.
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