ArticleHuman mutation2015
Structural and Functional Impact of Parkinson Disease-Associated Mutations in the E3 Ubiquitin Ligase Parkin.
Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- The Intersection of Mitophagy and Autism Spectrum Disorder: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism.Brain : a journal of neurology · 2017Pooled it
- Unraveling the core: hub genes bridging familial and sporadic Parkinson's disease.Journal of neurology · 2026Article
- miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A.Molecular neurodegeneration advances · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain.Molecular neurobiology · 2025Article
- Dopamine neuron dysfunction and loss in the PrknR275W mouse model of juvenile parkinsonism.Brain : a journal of neurology · 2024Article
- Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W.Cells · 2024Article
- Naturally occurring hyperactive variants of human parkin.Communications biology · 2024Article
- Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PRKN-linked familial Parkinson's disease: cellular and molecular mechanisms of disease-linked variants.Cellular and molecular life sciences : CMLS · 2024Review
- Intracellular delivery of Parkin-RING0-based fragments corrects Parkin-induced mitochondrial dysfunction through interaction with SLP-2.Journal of translational medicine · 2024Article
- Article
- Systematic Functional Analysis ofCells · 2022Article
- Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion ofMolecular syndromology · 2022Article
- Review
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Distinct phosphorylation signals drive acceptor versus free ubiquitin chain targeting by parkin.The Biochemical journal · 2022Article
- Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement.Biomolecules · 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the PARKIN/PARK2 gene that result in loss-of-function of the encoded, neuroprotective E3 ubiquitin ligase Parkin cause recessive, familial early-onset Parkinson disease. As an increasing number of rare Parkin sequence variants with unclear pathogenicity are identified, structure-function analyses will be critical to determine their disease relevance. Depending on the specific amino acids affected, several distinct pathomechanisms can result in loss of Parkin function. These include disruption of overall Parkin folding, decreased solubility, and protein aggregation. However pathogenic effects can also result from misregulation of Parkin autoinhibition and of its enzymatic functions. In addition, interference of binding to coenzymes, substrates, and adaptor proteins can affect its catalytic activity too. Herein, we have performed a comprehensive structural and functional analysis of 21 PARK2 missense mutations distributed across the individual protein domains. Using this combined approach, we were able to pinpoint some of the pathogenic mechanisms of individual sequence variants. Similar analyses will be critical in gaining a complete understanding of the complex regulations and enzymatic functions of Parkin. These studies will not only highlight the important residues, but will also help to develop novel therapeutics aimed at activating and preserving an active, neuroprotective form of Parkin.
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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.