ArticlePLoS computational biology2022
The properties of human disease mutations at protein interfaces.
Article in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 42 citations in OpenAlex.
- A simple probabilistic AlphaFold interaction score.Protein science : a publication of the Protein Society · 2026Article
- Why variant effect predictors and multiplexed assays agree and disagree.Nature communications · 2026Article
- Beyond contacts: The important role of the support region in protein complex assembly.Protein science : a publication of the Protein Society · 2026Article
- The Performance ofHuman mutation · 2026Article
- Generalizable and scalable protein stability prediction with rewired protein generative models.Nature communications · 2025Article
- COCOMAPS 2.0: a web server for identifying, analyzing, and visualizing atomic interactions at the interface of biomolecular complexes.Bioinformatics (Oxford, England) · 2025Article
- Calibrated Variant Effect Prediction at the Residue Level Using Conditional Score Distributions.bioRxiv : the preprint server for biology · 2025Article
- Unsupervised learning reveals landscape of local structural motifs across protein classes.Bioinformatics (Oxford, England) · 2025Article
- Leveraging Artificial Intelligence and Machine Learning for Characterizing Protein Corona, Nanobiological Interactions, and Advancing Drug Discovery.Bioengineering (Basel, Switzerland) · 2025Review
- Complementary Roles of Structure and Variant Effect Predictors in RyR1 Clinical Interpretation.Human mutation · 2025Article
- Protein structural context of cancer mutations reveals molecular mechanisms and candidate driver genes.Cell reports · 2024Article
- AAindexNC: Estimating the Physicochemical Properties of Non-Canonical Amino Acids, Including Those Derived from the PDB and PDBeChem Databank.International journal of molecular sciences · 2024Article
- Deep mutational scanning quantifies DNA binding and predicts clinical outcomes of PAX6 variants.Molecular systems biology · 2024Article
- ALS-Associated KIF5A Mutation Causes Locomotor Deficits Associated with Cytoplasmic Inclusions, Alterations of Neuromuscular Junctions, and Motor Neuron Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Missense3D-PPI: A Web Resource to Predict the Impact of Missense Variants at Protein Interfaces Using 3D Structural Data.Journal of molecular biology · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.American journal of human genetics · 2023Article
- An Assessment of Quaternary Structure Functionality in Homomer Protein Complexes.Molecular biology and evolution · 2023Article
- Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.Molecular cell · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.medRxiv : the preprint server for health sciences · 2023Article
- Distinct Interaction Modes for the Eukaryotic RNA Polymerase Alpha-like Subunits.Molecular and cellular biology · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The assembly of proteins into complexes and their interactions with other biomolecules are often vital for their biological function. While it is known that mutations at protein interfaces have a high potential to be damaging and cause human genetic disease, there has been relatively little consideration for how this varies between different types of interfaces. Here we investigate the properties of human pathogenic and putatively benign missense variants at homomeric (isologous and heterologous), heteromeric, DNA, RNA and other ligand interfaces, and at different regions in proteins with respect to those interfaces. We find that different types of interfaces vary greatly in their propensity to be associated with pathogenic mutations, with homomeric heterologous and DNA interfaces being particularly enriched in disease. We also find that residues that do not directly participate in an interface, but are close in three-dimensional space, show a significant disease enrichment. Finally, we observe that mutations at different types of interfaces tend to have distinct property changes when undergoing amino acid substitutions associated with disease, and that this is linked to substantial variability in their identification by computational variant effect predictors.
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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 Socratic graph.