ArticleEuropean journal of human genetics : EJHG2018
De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca
Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Customized multigene panels in epilepsy: the best things come in small packages.Neurogenetics · 2020Pooled it
- BK channel activity in skin fibroblasts from patients with neurological disorder.Channels (Austin, Tex.) · 2025Article
- The mechanism of CaThe Journal of biological chemistry · 2025Article
- A Comprehensive Overview of the Current Status and Advancements in Various Treatment Strategies against Epilepsy.ACS pharmacology & translational science · 2024Review
- Evaluation of fourChannels (Austin, Tex.) · 2024Article
- Small Molecule NS11021 Promotes BK Channel Activation by Increasing Inner Pore Hydration.Journal of chemical information and modeling · 2024Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- Interplay of epilepsy and long-term potentiation: implications for memory.Frontiers in neuroscience · 2024Review
- Large conductance voltage-and calcium-activated KFrontiers in pharmacology · 2024Review
- Epigenetics of the far northern Yakutian population.Clinical epigenetics · 2023Article
- Disease-associated KCNMA1 variants decrease circadian clock robustness in channelopathy mouse models.The Journal of general physiology · 2023Article
- Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.Neurogenetics · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- CaInternational journal of molecular sciences · 2023Review
- KCurrent neuropharmacology · 2023Review
- Article
- Whole-genome sequencing illuminates multifaceted targets of selection to humic substances in Eurasian perch.Molecular ecology · 2022Article
- Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Homology modeling and molecular docking simulation of martentoxin as a specific inhibitor of the BK channel.Annals of translational medicine · 2022Article
- Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study.Brain : a journal of neurology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 10 institutions in 4 countries.
Funding
Abstract
Epilepsy is one of the most common neurological diseases and it causes profound morbidity and mortality. We identified the first de novo variant in KCNMA1 (c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S)) variant markedly increased the macroscopic potassium current by increasing both the channel open probability and channel open dwell time. The c.2984 A > G (p.(N995S)) variant did not affect the calcium sensitivity of the channel. We also identified three other variants of unknown significance (c.1554 G > T (p.(K518N)), c.1967A > C (p.(E656A)), and c.3476 A > G (p.(N1159S))) in three separate patients with divergent epileptic phenotypes. However, these variants did not affect the BK potassium current, and are therefore unlikely to be disease-causing. These results demonstrate that BK channel variants can cause epilepsy without paroxysmal dyskinesia. The underlying molecular mechanism can be increased activation of the BK channel by increased sensitivity to the voltage-dependent activation without affecting the sensitivity to the calcium-dependent activation. Our data suggest that the BK channel may represent a drug target for the treatment of epilepsy. Our data highlight the importance of functional electrophysiological studies of BK channel variants in distinguishing whether a genomic variant of unknown significance is a disease-causing variant or a benign variant.
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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.