ArticleGenome research2021
Three-dimensional missense tolerance ratio analysis.
Article in Genome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Article
- Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification.medRxiv : the preprint server for health sciences · 2026Article
- Mice carrying a GluN2B protein-truncating variant have altered NMDA receptor subunit composition and their behavior recapitulates patient phenotypes.Cellular and molecular life sciences : CMLS · 2026Article
- KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Article
- Ligand distances as key predictors of pathogenicity and function in NMDA receptors.Human molecular genetics · 2025Article
- A unified analysis of evolutionary and population constraint in protein domains highlights structural features and pathogenic sites.Communications biology · 2024Article
- De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.Human molecular genetics · 2024Article
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Clinical and functional consequences of GRIA variants in patients with neurological diseases.Cellular and molecular life sciences : CMLS · 2023Article
- De novo CLPTM1 variants with reduced GABAEpilepsia · 2023Article
- Classification of missense variants in the N-methyl-d-aspartate receptor GRIN gene family as gain- or loss-of-function.Human molecular genetics · 2023Article
- Functional effects of disease-associated variants reveal that the S1-M1 linker of the NMDA receptor critically controls channel opening.Cellular and molecular life sciences : CMLS · 2023Article
- Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis.Molecular pharmacology · 2023Article
- Compendium of proteins containing segments that exhibit zero-tolerance to amino acid variation in humans.Protein science : a publication of the Protein Society · 2022Article
- The 3D mutational constraint on amino acid sites in the human proteome.Nature communications · 2022Article
- Opportunities for Precision Treatment ofThe Journal of pharmacology and experimental therapeutics · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
A wealth of genetic information is available describing single-nucleotide variants in the human population that appear to be well-tolerated and in and of themselves do not confer disease. These variant data sets contain signatures about the protein structure-function relationships and provide an unbiased view of various protein functions in the context of human health. This information can be used to determine regional intolerance to variation, defined as the missense tolerance ratio (MTR), which is an indicator of stretches of the polypeptide chain that can tolerate changes without compromising protein function in a manner that impacts human health. This approach circumvents the lack of comprehensive data by averaging the data from adjacent residues on the polypeptide chain. We reasoned that many motifs in proteins consist of nonadjacent residues, but together function as a unit. We therefore developed an approach to analyze nearest neighbors in three-dimensional space as determined by crystallography rather than on the polypeptide chain. We used members of the
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.