ArticleNature communications2024
A mutational atlas for Parkin proteostasis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 50 citations in OpenAlex.
- Why variant effect predictors and multiplexed assays agree and disagree.Nature communications · 2026Article
- Molecular dynamics simulations of intrinsically disordered protein regions enable biophysical interpretation of variant-effect predictors.HGG advances · 2026Article
- Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.Annals of neurology · 2026Article
- VEFill: accurate and generalizable deep mutational scanning score imputation across protein domains.Molecular systems biology · 2026Article
- Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- Supervised learning of protein variant effects across large-scale mutagenesis datasets.Protein science : a publication of the Protein Society · 2026Article
- Determining the intra-residue correlation of missense variant impact using MAVE scores: implications for the ACMG/AMP PM5 criterion for DNA variant classification.Genome medicine · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- A near-complete map of human cytosolic degrons and their relevance for disease.Science advances · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- From retina to brain: retinal dysfunction and dopaminergic neurodegeneration inFrontiers in cell and developmental biology · 2026Article
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR.Nature structural & molecular biology · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- acmgscaler: an R package and Colab for standardized gene-level variant effect score calibration within the ACMG/AMP framework.Bioinformatics (Oxford, England) · 2025Article
- Variant scoring tools for deep mutational scanning.Molecular systems biology · 2025Review
- The Juvenile Parkinson's Disease Mutation C212Y Impairs Mitochondrial Homeostasis in a Caenorhabditis elegans Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- VEFill: a model for accurate and generalizable deep mutational scanning score imputation across protein domains.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Proteostasis can be disturbed by mutations affecting folding and stability of the encoded protein. An example is the ubiquitin ligase Parkin, where gene variants result in autosomal recessive Parkinsonism. To uncover the pathological mechanism and provide comprehensive genotype-phenotype information, variant abundance by massively parallel sequencing (VAMP-seq) is leveraged to quantify the abundance of Parkin variants in cultured human cells. The resulting mutational map, covering 9219 out of the 9300 possible single-site amino acid substitutions and nonsense Parkin variants, shows that most low abundance variants are proteasome targets and are located within the structured domains of the protein. Half of the known disease-linked variants are found at low abundance. Systematic mapping of degradation signals (degrons) reveals an exposed degron region proximal to the so-called "activation element". This work provides examples of how missense variants may cause degradation either via destabilization of the native protein, or by introducing local signals for degradation.
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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.