ArticleEMBO molecular medicine2014
Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Role for TREK-1 as a polymodal sensor and regulator of cell activity.Channels (Austin, Tex.) · 2026Review
- Current Topics of Progressive Cardiac Conduction Disease.Journal of arrhythmia · 2026Review
- The diabetes-associated KDiabetologia · 2026Article
- KPharmaceuticals (Basel, Switzerland) · 2026Review
- Swapped and non-swapped TRAAK states co-exist in membranes at a ratio influenced by temperature.Nature communications · 2026Article
- Cardiac Manifestations ofHealth science reports · 2026Review
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Genetic Basis of Brugada Syndrome.Biomedicines · 2025Review
- Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the KNature communications · 2024Article
- Electrophysiological Effects of the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor Dapagliflozin on Human Cardiac Potassium Channels.International journal of molecular sciences · 2024Article
- BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy.The Journal of general physiology · 2023Article
- A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.Phenomics (Cham, Switzerland) · 2023Article
- A Novel Locus on 6p21.2 for Cancer Treatment-Induced Cardiac Dysfunction Among Childhood Cancer Survivors.Journal of the National Cancer Institute · 2022Article
- Uncovering the Genetic Etiology of the (Posttherapy) Broken Heart.Journal of the National Cancer Institute · 2022Article
- Two-Pore-Domain Potassium (KCells · 2021Review
- A KCNK16 mutation causing TALK-1 gain of function is associated with maturity-onset diabetes of the young.JCI insight · 2021Article
- Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Article
- Recognition and clinical implications of high prevalence of migraine in patients with Brugada syndrome and drug-induced type 1 Brugada pattern.Journal of cardiovascular electrophysiology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene.
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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.