ArticleAmerican journal of human genetics2017
De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Genome-wide association meta-analyses of drug-resistant epilepsy.EBioMedicine · 2025Pooled it
- Data-Driven Insights into Hyperkinetic Disorders in Neurodevelopmental Syndromes and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Clinical and Neurodevelopmental Characteristics of Paralogous Gain-of-Function Variants at GRIA2 p.Gly792 and GRIA3 p.Gly803.Clinical genetics · 2025Article
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- Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.ACS pharmacology & translational science · 2025Review
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- 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
- Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.Brain : a journal of neurology · 2024Article
- Mutation in the GRIA4 Gene Presenting as ESES: Expanding the Genetic Landscape of ESES.Annals of Indian Academy of Neurology · 2024Article
- Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder.Genes, brain, and behavior · 2024Article
- Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice.Frontiers in genetics · 2024Article
- Branched-chain keto acids promote an immune-suppressive and neurodegenerative microenvironment in leptomeningeal disease.bioRxiv : the preprint server for biology · 2023Article
- A Pathogenic Missense Mutation in Kainate Receptors Elevates Dendritic Excitability and Synaptic Integration through Dysregulation of SK Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Clinical and functional consequences of GRIA variants in patients with neurological diseases.Cellular and molecular life sciences : CMLS · 2023Article
- Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.Acta neuropathologica communications · 2023Article
- BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.European journal of human genetics : EJHG · 2023Article
- Movement Disorders inMovement disorders clinical practice · 2023Article
- A Swedish Familial Genome-Wide Haplotype Analysis Identified Five Novel Breast Cancer Susceptibility Loci on 9p24.3, 11q22.3, 15q11.2, 16q24.1 and Xq21.31.International journal of molecular sciences · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome.Genome biology · 2022Article
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism. The fourth variant in the SYTANLAAF motif most likely results in reduced permeability. The variant in the extracellular domain potentially interferes with the binding between the monomers. On the basis of clinical information and genetic results, and the fact that other subunits of the AMPA receptor have already been associated with neurodevelopmental disorders, we suggest that pathogenic de novo variants in GRIA4 lead to intellectual disability with or without seizures, gait abnormalities, problems of social behavior, and other variable features.
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