ArticleAmerican journal of human genetics2014
Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis 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
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
- Common X-Chromosome Variants Are Associated with Parkinson Disease Risk.Annals of neurology · 2021Pooled it
- RAB39B gene mutations are not linked to familial Parkinson's disease in China.Scientific reports · 2016Trial
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Heterogenous Neuropathology in a Pedigree with RAB39B-Related Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Genetic and environmental risk factors of Parkinsonism.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models.Acta neuropathologica communications · 2026Article
- A narrative review of serum biomarkers in progressive supranuclear palsy, corticobasal syndrome, and related disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Prenatal diagnosis of distal Xq28 duplication syndrome: case reports and literature review.Molecular cytogenetics · 2026Article
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- The Role of the Golgi Apparatus in Neurodegeneration.Sub-cellular biochemistry · 2026Review
- Waisman Syndrome: A Novel RAB39B Mutation in X-Linked Parkinsonism with Basal Ganglia Calcification and Literatures Review.Movement disorders clinical practice · 2025Article
- Soma-localized Rab39 inhibits synaptic autophagy by controlling trafficking of Atg9 vesicles.The EMBO journal · 2025Article
- Genetics and Phenotypes of Late-Onset Neurodegeneration in Neurodevelopmental Disorders.Cureus · 2025Review
- The RAB32 p.Ser71Arg Variant in Parkinsonisms: Insights from a Large Italian Cohort.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Rare Copy Number Variants Intersecting Parkinson's-associated Genes in a Cohort of children With Autism Spectrum Disorders.Neuroscience insights · 2025Article
- RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.The Lancet. Neurology · 2024Article
- X-Linked Levodopa-Responsive Parkinsonism-Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review.Movement disorders clinical practice · 2024Review
- A neurodevelopmental disorder associated with a loss-of-function missense mutation in RAB35.The Journal of biological chemistry · 2024Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
33 authors at 16 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders.
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.