ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates neuronal migration through an amyloid-β precursor protein-dependent mechanism.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 44 citations in OpenAlex.
- Insights in the underlying pathophysiology of brain malformations associated with VRK1-related syndrome derived from fetal neuropathology.Journal of neuropathology and experimental neurology · 2025Article
- Identification of a circRNA-miRNA-mRNA interactome associated with Parkinson's disease progression.Journal of Parkinson's disease · 2025Article
- Severe hyperCKaemia and decreased sarcolemmal dysferlin in VRK1-associated distal spinal muscular atrophy: a case report.BMJ neurology open · 2025Article
- Pontocerebellar hypoplasia: a review from 1912 to 2022.Brain communications · 2025Review
- Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.BMC medical genomics · 2024Article
- VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system.JCI insight · 2022Article
- Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity.Nucleic acids research · 2022Article
- Inhibition of VRK1 suppresses proliferation and migration of vascular smooth muscle cells and intima hyperplasia after injury via mTORC1/β-catenin axis.BMB reports · 2022Article
- Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia.Neurology. Genetics · 2021Article
- Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation.Cancers · 2020Article
- VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy.Annals of clinical and translational neurology · 2020Article
- Motor neuron diseases caused by a novel VRK1 variant - A genotype/phenotype study.Annals of clinical and translational neurology · 2019Article
- VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes.Scientific reports · 2019Article
- A novel mutation in VRK1 associated with distal spinal muscular atrophy.Journal of human genetics · 2019Article
- Whole-exome sequencing in fetuses with central nervous system abnormalities.Journal of perinatology : official journal of the California Perinatal Association · 2018Article
- Vrk1 partial Knockdown in Mice Results in Reduced Brain Weight and Mild Motor Dysfunction, and Indicates Neuronal VRK1 Target Pathways.Scientific reports · 2018Article
- What's new in pontocerebellar hypoplasia? An update on genes and subtypes.Orphanet journal of rare diseases · 2018Review
- Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development.American journal of human genetics · 2017Article
- Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2.Journal of virology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH) is an infantile SMA variant with additional manifestations, particularly severe microcephaly. We previously identified a nonsense mutation in Vaccinia-related kinase 1 (VRK1), R358X, as a cause of SMA-PCH. VRK1-R358X is a rare founder mutation in Ashkenazi Jews, and additional mutations in patients of different origins have recently been identified. VRK1 is a nuclear serine/threonine protein kinase known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis. However, VRK1 was not known to have neuronal functions before its identification as a gene mutated in SMA-PCH. Here we show that VRK1-R358X homozygosity results in lack of VRK1 protein, and demonstrate a role for VRK1 in neuronal migration and neuronal stem cell proliferation. Using shRNA in utero electroporation in mice, we show that Vrk1 knockdown significantly impairs cortical neuronal migration, and affects the cell cycle of neuronal progenitors. Expression of wild-type human VRK1 rescues both proliferation and migration phenotypes. However, kinase-dead human VRK1 rescues only the migration impairment, suggesting the role of VRK1 in neuronal migration is partly noncatalytic. Furthermore, we found that VRK1 deficiency in human and mouse leads to downregulation of amyloid-β precursor protein (APP), a known neuronal migration gene. APP overexpression rescues the phenotype caused by Vrk1 knockdown, suggesting that VRK1 affects neuronal migration through an APP-dependent mechanism.
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.