ArticleProceedings of the National Academy of Sciences of the United States of America2007
Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.Molecular psychiatry · 2015Pooled it
- Glutamatergic candidate genes in autism spectrum disorder: an overview.Journal of neural transmission (Vienna, Austria : 1996) · 2014Pooled it
- Epilepsy as a Disorder of Neuroimmune Metabolism: The Kynurenine Pathway as a Link Between Cognitive and Psychiatric Dysfunction.Biomolecules · 2026Review
- AMPAR Subunit Gene Expression Marks a Synaptic Transcriptional State in Lower-Grade Glioma.Brain sciences · 2026Article
- Phosphoproteomic profiling reveals reversal of dysregulated kinase signaling by nitric oxide inhibition in the Shank3 mouse model of autism.Scientific reports · 2026Article
- Subgroup-Specific Associations of GRIA Genes Encoding AMPA Glutamate Receptor Subunits with Patient Survival in Medulloblastoma.Neuromolecular medicine · 2026Article
- BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons.Research square · 2026Article
- Reclassification of theFrontiers in genetics · 2026Article
- Chromatin Profiling Reveals Distinct Male and Female Trajectories for Developmental Learning Potential.Developmental neurobiology · 2026Article
- Review
- Non-Convulsive Status Epilepticus and Mild Neurodevelopmental Phenotype in a Female with a Novel p.Thr657Ala Variant in theChildren (Basel, Switzerland) · 2025Article
- Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases.bioRxiv : the preprint server for biology · 2025Article
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- Disrupted diencephalon development and neuropeptidergic pathways in zebrafish with autism-risk mutations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Impact of Psychological Stress and Spontaneous Tumour Regression on the Hippocampal Proteome in a Mouse Model of Breast Cancer.Journal of neurochemistry · 2025Article
- Exploring the Landscape of Pre- and Post-Synaptic Pediatric Disorders with Epilepsy: A Narrative Review on Molecular Mechanisms Involved.International journal of molecular sciences · 2024Review
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Genetic Diversity in Schizophrenia: Developmental Implications of Ultra-Rare, Protein-Truncating Mutations.Genes · 2024Review
- Rare variation in non-coding regions with evolutionary signatures contributes to autism spectrum disorder risk.Cell genomics · 2024Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 11 institutions in 6 countries.
Funding
Abstract
Ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (iGluRs) mediate the majority of excitatory synaptic transmission in the CNS and are essential for the induction and maintenance of long-term potentiation and long-term depression, two cellular models of learning and memory. We identified a genomic deletion (0.4 Mb) involving the entire GRIA3 (encoding iGluR3) by using an X-array comparative genomic hybridization (CGH) and four missense variants (G833R, M706T, R631S, and R450Q) in functional domains of iGluR3 by sequencing 400 males with X-linked mental retardation (XLMR). Three variants were found in males with moderate MR and were absent in 500 control males. Expression studies in HEK293 cells showed that G833R resulted in a 78% reduction of iGluR3 due to protein misfolding. Whole-cell recording studies of iGluR3 homomers in HEK293 cells revealed that neither iGluR3-M706T (S2 domain) nor iGluR3-R631S (near channel core) had substantial channel function, whereas R450Q (S1 domain) was associated with accelerated receptor desensitization. When forming heteromeric receptors with iGluR2 in HEK293 cells, all four iGluR3 variants had altered desensitization kinetics. Our study provides the genetic and functional evidence that mutant iGluR3 with altered kinetic properties is associated with moderate cognitive impairment in humans.
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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.