ArticleNature communications2014
Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
What it found
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Who cites it
130 citing papers in PubMed, 200 citations in OpenAlex.
- Quantitative analysis of trafficking defects induced by heterozygous expression of hERG voltage sensor domain variants.Channels (Austin, Tex.) · 2026Article
- NS1643 enhances the activity of T1019PfsX38 and Q1070X hERG channels associated with long QT syndrome type 2.Pflugers Archiv : European journal of physiology · 2026Article
- Forward genetics reveals a conserved CNBHD-CNBHD interface that restrains EAG channel activation to regulate sleep.PLoS genetics · 2026Article
- Structural determinants at KCNE4 position 145 govern Kv1.3 channel function.The Journal of general physiology · 2026Article
- Functional characterization and allele-specific RNA interference-based rescue of KCNH2 p.F68C variant associated with long QT syndrome.Molecular genetics and genomics : MGG · 2026Article
- Allosteric Mechanisms Underlying Long QT Syndrome Type 2 (LQT2)-Associated Mutations in hERG Channels.bioRxiv : the preprint server for biology · 2026Article
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- AProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Personalized in vitro models reveal functional impact of aHeart rhythm O2 · 2026Article
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Kv11.1 (hERG) Protein Interaction Networks Connect Endocytic Trafficking to Polygenic Influences on Cardiac Repolarization.bioRxiv : the preprint server for biology · 2026Article
- Case Report: Association of a rare single nucleotide variant in the KCNH2 gene with drug-induced QT prolongation.Frontiers in genetics · 2026Article
- Case Report Series: Genetic and clinical characterization of long QT syndrome in admixed Ecuadorian patients and its implications for sudden cardiac death risk.Frontiers in cardiovascular medicine · 2026Article
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Mapping the Functional Landscape ofmedRxiv : the preprint server for health sciences · 2025Article
- Early-stage Determinants of T1-S1 Conformations in Kv1.3 Channels.Journal of molecular biology · 2025Article
- High-throughput screens identify genotype-specific therapeutics for channelopathies.JCI insight · 2025Article
- KCNH2-L693P Causes Long QT Syndrome Type 2 Through hERG Channel Dysfunction: Functional Validation of a Variant of Uncertain Significance.Molecular genetics & genomic medicine · 2025Article
- Sudden Death-AssociatedbioRxiv : the preprint server for biology · 2025Article
- Disease-associated Kv1.3 Variants are Energy Compromised with Impaired Nascent Chain Folding.Journal of molecular biology · 2025Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
It has been suggested that deficient protein trafficking to the cell membrane is the dominant mechanism associated with type 2 Long QT syndrome (LQT2) caused by Kv11.1 potassium channel missense mutations, and that for many mutations the trafficking defect can be corrected pharmacologically. However, this inference was based on expression of a small number of Kv11.1 mutations. We performed a comprehensive analysis of 167 LQT2-linked missense mutations in four Kv11.1 structural domains and found that deficient protein trafficking is the dominant mechanism for all domains except for the distal carboxy-terminus. Also, most pore mutations--in contrast to intracellular domain mutations--were found to have severe dominant-negative effects when co-expressed with wild-type subunits. Finally, pharmacological correction of the trafficking defect in homomeric mutant channels was possible for mutations within all structural domains. However, pharmacological correction is dramatically improved for pore mutants when co-expressed with wild-type subunits to form heteromeric channels.
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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.