ArticleGenetics2017
Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions.
Article in Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
69 citing papers in PubMed.
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- Alanine scanning of the yeast killer toxin K2 reveals key residues for activity, gain-of-function variants, and supports prediction of precursor processing and 3D structure.Journal of structural biology: X · 2026Article
- VEFill: accurate and generalizable deep mutational scanning score imputation across protein domains.Molecular systems biology · 2026Article
- Article
- Predicting antifolate resistance in the unculturable fungal pathogen Pneumocystis jirovecii.PLoS genetics · 2026Article
- Supervised learning of protein variant effects across large-scale mutagenesis datasets.Protein science : a publication of the Protein Society · 2026Article
- Deconvolving mutation effects on protein stability and function with disentangled protein language models.bioRxiv : the preprint server for biology · 2026Article
- Assessing the Performance of Mass Spectrometry Search Strategies in Identifying Translational Errors Using PDX Proteomics Data.Molecular & cellular proteomics : MCP · 2026Article
- Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025Article
- Synaptobrevin-2 disease variants reveal spatial constraints within the presynaptic active zone.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dissecting the effects of single amino acid substitutions in SARS-CoV-2 Mpro.Protein science : a publication of the Protein Society · 2025Article
- Deep mutational scanning reveals a de novo disulfide bond and combinatorial mutations for engineering thermostable myoglobin.Protein science : a publication of the Protein Society · 2025Article
- Mapping the sclerostin-LRP4 binding interface identifies critical interaction hotspots in loops 1 and 3 of sclerostin.FEBS letters · 2025Article
- Accelerated enzyme engineering by machine-learning guided cell-free expression.Nature communications · 2025Article
- Rational design of monomeric IL37 variants guided by stability and dynamical analyses of IL37 dimers.Computational and structural biotechnology journal · 2024Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- A fitness distribution law for amino-acid replacements.bioRxiv : the preprint server for biology · 2024Article
- FUSE: Improving the estimation and imputation of variant impacts in functional screening.Cell genomics · 2024Article
- RudS: bacterial desulfidase responsible for tRNA 4-thiouridine de-modification.Nucleic acids research · 2024Article
- An invariant C-terminal tryptophan in McdB mediates its interaction and positioning function with carboxysomes.Molecular biology of the cell · 2024Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Mutagenesis is a widely used method for identifying protein positions that are important for function or ligand binding. Advances in high-throughput DNA sequencing and mutagenesis techniques have enabled measurement of the effects of nearly all possible amino acid substitutions in many proteins. The resulting large-scale mutagenesis data sets offer a unique opportunity to draw general conclusions about the effects of different amino acid substitutions. Thus, we analyzed 34,373 mutations in 14 proteins whose effects were measured using large-scale mutagenesis approaches. Methionine was the most tolerated substitution, while proline was the least tolerated. We found that several substitutions, including histidine and asparagine, best recapitulated the effects of other substitutions, even when the identity of the wild-type amino acid was considered. The effects of histidine and asparagine substitutions also correlated best with the effects of other substitutions in different structural contexts. Furthermore, highly disruptive substitutions like aspartic and glutamic acid had the most discriminatory power for detecting ligand interface positions. Our work highlights the utility of large-scale mutagenesis data, and our conclusions can help guide future single substitution mutational scans.
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