ReviewEpilepsia2019
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations.
Review in Epilepsia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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
50 citing papers in PubMed, 79 citations in OpenAlex.
- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- Focal Cortical Dysplasia Type II: Somatic Mutations, Molecular Mechanisms, and Integrative Multi-Omics Framework.CNS neuroscience & therapeutics · 2026Review
- Pathological disruption of CELF2 shuttling causes neuronal hyperactivity, learning deficits, and seizures.The Journal of clinical investigation · 2026Article
- The Clinical Spectrum and Neurodevelopmental Pathogenesis of KPTN-Related Disorder in a Mouse Model.Annals of neurology · 2026Article
- Review
- Metabolic changes in mTOR pathway-associated cortical malformation.Frontiers in neuroscience · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Cell-cell communication dysregulation in tuberous sclerosis complex cortical tubers and focal cortical dysplasia.Acta neuropathologica communications · 2025Article
- Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype-Phenotype Relationships in the PI3K-AKT-MTOR Pathway.medRxiv : the preprint server for health sciences · 2025Article
- Surgical decision-making in adult patients with epilepsy related to germline mutations: A single-center study.The Journal of international medical research · 2025Observational
- Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology.Nature communications · 2025Article
- Autism Spectrum Disorder and Epilepsy: Pathogenetic Mechanisms and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Genotypic and clinical phenotypic analysis of DEPDC5 gene mutations.Neurogenetics · 2025Article
- NovelFrontiers in neuroscience · 2025Article
- Comprehensive analysis of plasma cell heterogeneity and immune interactions in multiple myeloma.Frontiers in immunology · 2025Article
- Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024Review
- The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.Genes & diseases · 2024Review
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex.American journal of medical genetics. Part A · 2024Article
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
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 3 institutions in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) pathway has been implicated in a growing number of malformations of cortical development (MCD) associated with intractable epilepsy. Mutations in single genes encoding mTOR pathway regulatory proteins have been linked to MCD such as focal cortical dysplasia (FCD) types IIa and IIb, hemimegalencephaly (HME), and megalencephaly. Recent studies have demonstrated that the GATOR1 protein complex, comprised of DEPDC5, NPRL3, and NPRL2, plays a pivotal role in regulating mTOR signaling in response to cellular amino acid levels and that mutations in DEPDC5, NPRL3, or NPRL2 are linked to FCD, HME, and seizures. Histopathological analysis of FCD and HME tissue specimens resected from individuals harboring DEPDC5, NPRL3, or NPRL2 gene mutations reveals hyperactivation of mTOR pathway signaling. Family pedigrees carrying mutations in either DEPDC5 or NPRL3 share clinical phenotypes of epilepsy and MCD, as well as intellectual and neuropsychiatric disabilities. Interestingly, some individuals with seizures associated with DEPDC5, NPRL3, or NPRL2 variants exhibit normal brain imaging suggesting either occult MCD or a role for these genes in non-lesional neocortical epilepsy. Mouse models resulting from knockdown or knockout of either Depdc5 or Nprl3 exhibit altered cortical lamination, neuronal dysmorphogenesis, and enhanced neuronal excitability as reported in models resulting from direct mTOR activation through expression of its canonical activator RHEB. The role of the GATOR1 proteins in regulating mTOR signaling suggest plausible options for mTOR inhibition in the treatment of epilepsy associated with mutations in DEPDC5, NPRL3, or NPRL2.
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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.