ArticleScientific reports2016
Gain-of-function defects of astrocytic Kir4.1 channels in children with autism spectrum disorders and epilepsy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pooled it
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- The role of astrocytes in autism spectrum disorder and associated syndromes: Evidence, animal models, mechanisms, and therapeutic potential.Zoological research · 2026Review
- Optimizing anti-seizure medication selection for epilepsy in EAST/SeSAME syndrome: Insights from DrugBank and STRING databases.Genes & diseases · 2026Article
- JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder.Molecular autism · 2026Article
- Aberrant astroglial Kir4.1 activation in the anterior cingulate cortex disrupts neuronal excitability and social behavior.Acta pharmaceutica Sinica. B · 2026Article
- Novel Mutations in KCNJ10 Gene Associated With SeSAME Syndrome: Rare Disorder With Possible Common Mutation.Molecular genetics & genomic medicine · 2026Article
- Beyond the synapse: Bassoon mutations drive epilepsy through Astrocyte-Neuron crosstalk.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Astroglial Kir4.1 and AQP4 Channels: Key Regulators of Potassium Homeostasis and Their Implications in Autism Spectrum Disorders.Cellular and molecular neurobiology · 2025Review
- Editorial: Pathogenic potassium channel variants in neurological disorders: from functional analysis to personalized pharmacological approaches.Frontiers in cellular neuroscience · 2025Article
- Astroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model.Nature communications · 2024Article
- Advancing Kir4.2 Channel Ligand Identification through Collision-Induced Affinity Selection Mass Spectrometry.ACS chemical biology · 2024Article
- The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity.Antioxidants (Basel, Switzerland) · 2023Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model.International journal of molecular sciences · 2022Article
- Glial Contributions to Lafora Disease: A Systematic Review.Biomedicines · 2022Review
- Modelling Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) Using Mice and Zebrafish.International journal of molecular sciences · 2022Review
- Trehalose Treatment in Zebrafish Model of Lafora Disease.International journal of molecular sciences · 2022Article
- EnhancingGenes · 2022Article
- Zebrafish Modeling of Autism Spectrum Disorders, Current Status and Future Prospective.Frontiers in psychiatry · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10. We detected germline heterozygous KCNJ10 variants in 19/175 affected children. Epileptic spasms with dysregulated sensory processing represented the main disease phenotype. When investigated on astrocyte-like cells, the p.R18Q mutation exerted a gain-of-function effect by enhancing Kir4.1 membrane expression and current density. Similarly, the p.R348H variant led to gain of channel function through hindrance of pH-dependent current inhibition. The frequent polymorphism p.R271C seemed, instead, to have no obvious functional effects. Our results confirm that variants in KCNJ10 deserve attention in autism-epilepsy, and provide insight into the molecular mechanisms of autism and seizures. Similar to neurons, astrocyte dysfunction may result in abnormal synaptic transmission and electrical discharge, and should be regarded as a possible pharmacological target in autism-epilepsy.
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.