ArticleMolecular psychiatry2024
Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Unraveling the Role of Wnt Signaling Pathway in the Pathogenesis of Autism Spectrum Disorder (ASD): A Systematic Review.Molecular neurobiology · 2025Pooled it
- Autism-like behavior induced by conditional ablation of the Bassoon gene in GABAergic interneurons.Molecular psychiatry · 2026Article
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Transcriptome profiling of neurexin- and neuroligin-deficient Caenorhabditis elegans reveals pathways underlying developmental and behavioral dysfunction.Research square · 2026Article
- FOXG1 Hierarchically Shapes Synaptic Functions in Striatal iSPNs and Contributes to ASD Etiology.Neuroscience bulletin · 2026Article
- Article
- Neurogenin-2 Reprograms Human Microglial Lineage Cells into Neurons In Vitro and in Chimeric Brains.bioRxiv : the preprint server for biology · 2026Article
- Distinct synaptic mechanisms underlie NRXN1 variant and disorder background-dependent phenotypes in iPSC-derived neurons.Cell reports · 2026Article
- Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions.Cell reports · 2026Article
- Does Altered Membrane Glycosylation Contribute to Neurodevelopmental Dysfunction in Autism Spectrum Disorder?Membranes · 2026Review
- Insertion of rare autism variants in synaptic genes induce novel behavioral phenotypes inbioRxiv : the preprint server for biology · 2025Article
- Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.Nature communications · 2025Article
- Molecular and developmental deficits in Smith-Magenis syndrome human stem cell-derived cortical neural models.American journal of human genetics · 2025Article
- Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus onNutrients · 2025Review
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Distinct Synaptic Mechanisms DrivebioRxiv : the preprint server for biology · 2025Article
- Cell-specific expression biases in human cortex of genes associated with neurodevelopmental disorders.Scientific reports · 2025Article
- Proteogenomic Insights Into Glioblastoma Evolution: Neuronal Reprogramming and Therapeutic Vulnerabilities.Brain tumor research and treatment · 2025Review
- Developmental Disturbances in Animal Models of Autism Spectrum Disorder.Developmental neurobiology · 2025Review
- Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutations in many synaptic genes are associated with autism spectrum disorders (ASD), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C mutation on human neurons has not been investigated. Here, we generated human knockin neurons with the NLGN3 R451C and NLGN3 null mutations. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses; meanwhile NLGN3 knockout neurons showed reduction in excitatory synaptic strengths. Moreover, overexpression of NLGN3 R451C recapitulated the synaptic enhancement in human neurons. Notably, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons corresponding to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASD.
Indexed as
Identifiers
What OpenQuestion holds
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.