ArticleAnnals of clinical and translational neurology2021
Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy.
Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- GRIN-related epilepsy in Chinese pediatric patients: a retrospective study of clinical, genetic, and mutant protein structural features in a tertiary center cohort.World journal of pediatrics : WJP · 2026Article
- Subconductance states in NMDA receptor variants are CaResearch square · 2026Article
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- Neurodevelopmental disorder-causing GRIN1 Y647S variant alters red blood cell physiology in mice.Physiological reports · 2026Article
- Context-dependent NMDA receptor dysfunction predicts seizure treatment in mice with human GluN1 variant.iScience · 2026Article
- An Integrative Approach to Identifying Neuroprotective Natural Compounds for Neurodevelopmental Disorders.International journal of molecular sciences · 2025Article
- Precision therapies for genetic epilepsies in 2025: Promises and pitfalls.Epilepsia open · 2025Article
- Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders.NPJ genomic medicine · 2025Article
- Identification of Immune-Related Biomarkers of Schizophrenia in the Central Nervous System Using Bioinformatic Methods and Machine Learning Algorithms.Molecular neurobiology · 2025Article
- Ligand distances as key predictors of pathogenicity and function in NMDA receptors.Human molecular genetics · 2025Article
- Article
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024Review
- WONOEP appraisal: Modeling early onset epilepsies.Epilepsia · 2024Review
- Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.Physiological research · 2024Review
- De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy.Methods in molecular biology (Clifton, N.J.) · 2024Review
- An integrated approach to evaluate the functional effects of disease-associated NMDA receptor variants.Neuropharmacology · 2023Article
- Classification of missense variants in the N-methyl-d-aspartate receptor GRIN gene family as gain- or loss-of-function.Human molecular genetics · 2023Article
- KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.Cell death and differentiation · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveGenetic variants in the GRIN genes that encode N-methyl-D-aspartate receptor (NMDAR) subunits have been identified in various neurodevelopmental disorders, including epilepsy. We identified a GRIN1 variant from an individual with early-onset epileptic encephalopathy, evaluated functional changes to NMDAR properties caused by the variant, and screened FDA-approved therapeutic compounds as potential treatments for the patient.
methodsWhole exome sequencing identified a missense variant in GRIN1. Electrophysiological recordings were made from Xenopus oocytes and transfected HEK cells to determine the NMDAR biophysical properties as well as the sensitivity to agonists and FDA-approved drugs that inhibit NMDARs. A beta-lactamase reporter assay in transfected HEK cells evaluated the effects of the variant on the NMDAR surface expression.
resultsA recurrent de novo missense variant in GRIN1 (c.1923G>A, p.Met641Ile), which encodes the GluN1 subunit, was identified in a pediatric patient with drug-resistant seizures and early-onset epileptic encephalopathy. In vitro analysis indicates that GluN1-M641I containing NMDARs showed enhanced agonist potency and reduced Mg
interpretationOur finding contributes to the understanding of the phenotype-genotype correlations of patients with GRIN1 gene variants, provides a molecular mechanism underlying the actions of this variant, and explores therapeutic strategies for treating GRIN1-related neurological conditions.
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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.