ArticleEMBO reports2014
Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy.
Article in EMBO reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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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.
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Who cites it
104 citing papers in PubMed, 187 citations in OpenAlex.
- The use of carbogen for interruption of febrile seizures - the randomized controlled CARDIF trial.PloS one · 2025Trial
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- GABASynapse (New York, N.Y.) · 2026Review
- Compound heterozygous SLC12A5 variants expand the molecular and functional spectrum of KCC2-developmental and epileptic encephalopathy.Epilepsia · 2026Article
- Structural basis for the ion selectivity of potassium-chloride cotransporter KCC4 revealed by cryo-EM titration.Biophysics reports · 2026Article
- Highly conserved ion binding sites are not all functionally relevant in mouse KCC4.Frontiers in molecular biosciences · 2025Article
- Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism.Human genomics · 2024Article
- Article
- Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation-Chloride Cotransporters in Rat Cortical Neurons.International journal of molecular sciences · 2024Article
- The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.Neurochemistry international · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.Frontiers in molecular neuroscience · 2024Article
- A novel pathogenicFrontiers in molecular neuroscience · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- De novo CLPTM1 variants with reduced GABAEpilepsia · 2023Article
- Rett and Rett-related disorders: Common mechanisms for shared symptoms?Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice.Cell reports. Medicine · 2023Article
- KFrontiers in cellular neuroscience · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 3 countries.
Funding
Abstract
The KCC2 cotransporter establishes the low neuronal Cl(-) levels required for GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability. However, no mutations in KCC2 have been documented in human disease. Here, we report two non-synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE). These variants reside in conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly impaired Cl(-)-extrusion capacities resulting in less hyperpolarized Gly equilibrium potentials (EG ly), and impair KCC2 stimulatory phosphorylation at serine 940, a key regulatory site. These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE.
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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.