ArticlePLoS computational biology2015
Increased Aggregation Is More Frequently Associated to Human Disease-Associated Mutations Than to Neutral Polymorphisms.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Small molecules rescue pathogenic POLGA aggregation and restore its functions in a mouse model of PEO.EMBO molecular medicine · 2026Article
- VAEBAC: a representation-learning framework for proteome-scale prediction of amyloidogenic proteins and functional stratification of nucleic-acid-binding proteins.Bioinformatics (Oxford, England) · 2026Article
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- Genomic structural equation modeling reveals shared genetic structure of cardiac function and structure-function association studies of CLCNKA mutations.Scientific reports · 2026Article
- Structural Insights Into Amyloid Polymorphism: The Impact of Glutamine to Norleucine Substitutions in GNNQQNY Aggregation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Genetic Functionalization of Protein-Based Biomaterials via Protein Fusions.Biomacromolecules · 2024Review
- N-glycosylation as a eukaryotic protective mechanism against protein aggregation.Science advances · 2024Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- A FRET-Based Assay for the Identification of PCNA Inhibitors.International journal of molecular sciences · 2023Article
- SNPeffect 5.0: large-scale structural phenotyping of protein coding variants extracted from next-generation sequencing data using AlphaFold models.BMC bioinformatics · 2023Article
- On a mechanistic impact of transmembrane tetramerization in the pathological activation of RTKs.Computational and structural biotechnology journal · 2023Article
- The First Homozygote Mutation c.499G>T (Asp167Tyr) in the RPE65 Gene Encoding Retinoid Isomerohydrolase Causing Retinal DystrophyCurrent issues in molecular biology · 2022Article
- Characterization of full-length p53 aggregates and their kinetics of formation.Biophysical journal · 2022Article
- Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure.Nature communications · 2022Article
- Whole-exome sequencing in a Japanese multiplex family identifies new susceptibility genes for intracranial aneurysms.PloS one · 2022Article
- Disease-Related Protein Variants of the Highly Conserved Enzyme PAPSS2 Show Marginal Stability and Aggregation in Cells.Frontiers in molecular biosciences · 2022Article
- A comparison of four technologies for detecting p53 aggregates in ovarian cancer.Frontiers in oncology · 2022Article
- Most myopathic lamin variants aggregate: a functional genomics approach for assessing variants of uncertain significance.NPJ genomic medicine · 2021Article
- Aggregation of gelsolin wild-type and G167K/R, N184K, and D187N/Y mutant peptides and inhibition.Molecular and cellular biochemistry · 2021Article
- Aggregation is a Context-Dependent Constraint on Protein Evolution.Frontiers in molecular biosciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein aggregation is a hallmark of over 30 human pathologies. In these diseases, the aggregation of one or a few specific proteins is often toxic, leading to cellular degeneration and/or organ disruption in addition to the loss-of-function resulting from protein misfolding. Although the pathophysiological consequences of these diseases are overt, the molecular dysregulations leading to aggregate toxicity are still unclear and appear to be diverse and multifactorial. The molecular mechanisms of protein aggregation and therefore the biophysical parameters favoring protein aggregation are better understood. Here we perform an in silico survey of the impact of human sequence variation on the aggregation propensity of human proteins. We find that disease-associated variations are statistically significantly enriched in mutations that increase the aggregation potential of human proteins when compared to neutral sequence variations. These findings suggest that protein aggregation might have a broader impact on human disease than generally assumed and that beyond loss-of-function, the aggregation of mutant proteins involved in cancer, immune disorders or inflammation could potentially further contribute to disease by additional burden on cellular protein homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
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.