ArticleNature medicine2009
A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.Human brain mapping · 2016Pooled it
- Effects of neuregulin 3 genotype on human prefrontal cortex physiology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Trial
- The Role of Loss-of-Function KCNH2 Variants in Cardiac Arrhythmias, Seizures and the Risk of Sudden Unexpected Death in Epilepsy.Journal of neurochemistry · 2026Review
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- An ER retention motif controls the heteromeric stoichiometry of hERG1a/1b channels.bioRxiv : the preprint server for biology · 2026Article
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Sudden Death-AssociatedbioRxiv : the preprint server for biology · 2025Article
- A privileged ER compartment for posttranslational heteromeric assembly of an ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A privileged ER compartment for post-translational heteromeric assembly of an ion channel.bioRxiv : the preprint server for biology · 2025Article
- Purkinje cell hyperexcitability and depressive-like behavior in mice lacking erg3 (ether-à-go-go-related gene) KScience advances · 2024Article
- An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.Biophysical journal · 2024Article
- Illuminating the druggable genome: Pathways to progress.Drug discovery today · 2024Review
- Imaging genomics: data fusion in uncovering disease heritability.Trends in molecular medicine · 2023Review
- Article
- DNA topoisomerase 2-associated proteins PATL1 and PATL2 regulate the biogenesis of hERG KProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Locus Coeruleus Neurons' Firing Pattern Is Regulated by ERG Voltage-Gated KInternational journal of molecular sciences · 2022Article
- Analysis ofGenes · 2022Article
- Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.Neuroscience and biobehavioral reviews · 2022Review
- The ERG1 KFrontiers in molecular neuroscience · 2022Review
- An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data.Molecular psychiatry · 2022Review
74 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 8 institutions in 6 countries.
Funding
Abstract
Organized neuronal firing is crucial for cortical processing and is disrupted in schizophrenia. Using rapid amplification of 5' complementary DNA ends in human brain, we identified a primate-specific isoform (3.1) of the ether-a-go-go-related K(+) channel KCNH2 that modulates neuronal firing. KCNH2-3.1 messenger RNA levels are comparable to full-length KCNH2 (1A) levels in brain but three orders of magnitude lower in heart. In hippocampus from individuals with schizophrenia, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A expression. A meta-analysis of five clinical data sets (367 families, 1,158 unrelated cases and 1,704 controls) shows association of single nucleotide polymorphisms in KCNH2 with schizophrenia. Risk-associated alleles predict lower intelligence quotient scores and speed of cognitive processing, altered memory-linked functional magnetic resonance imaging signals and increased KCNH2-3.1 mRNA levels in postmortem hippocampus. KCNH2-3.1 lacks a domain that is crucial for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K(+) current and a high-frequency, nonadapting firing pattern. These results identify a previously undescribed KCNH2 channel isoform involved in cortical physiology, cognition and psychosis, providing a potential new therapeutic drug target.
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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.