ArticleMolecular neuropsychiatry2016
A Mutation in NPAS3 That Segregates with Schizophrenia in a Small Family Leads to Protein Aggregation.
Article in Molecular neuropsychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations.Translational psychiatry · 2018Pooled it
- Assessment of Aggregation- and Condensation-Prone Regions of Proteins Involved in Neurodegenerative, Neurological and Mental-State Diseases.Biomolecules · 2026Article
- NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.Science advances · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Epigenetic Evidence Implies Disturbed Proteostasis and Potentially Protein Aggregation in Suicidality.Biomolecules · 2026Review
- Levels of aggregation of proteins related to mental illness, assayed by insolubility, vary across the brains of individuals.Scientific reports · 2026Article
- Protein aggregation identified in olfactory neuronal cells is associated with cognitive impairments in a subset of living schizophrenia patients.Molecular psychiatry · 2025Article
- Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.BioData mining · 2024Article
- Article
- Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.International journal of molecular sciences · 2023Article
- Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer's disease related proteins.Molecular neurodegeneration · 2023Article
- Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders.International journal of molecular sciences · 2022Review
- TRIOBP-1 Protein Aggregation Exists in Both Major Depressive Disorder and Schizophrenia, and Can Occur through Two Distinct Regions of the Protein.International journal of molecular sciences · 2022Article
- A Perspective on the Potential Involvement of Impaired Proteostasis in Neuropsychiatric Disorders.Biological psychiatry · 2022Review
- Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation.Journal of personalized medicine · 2021Article
- Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.Scientific reports · 2021Article
- The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development.International journal of molecular sciences · 2021Article
- Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder.Molecular psychiatry · 2019Article
- Protein misassembly and aggregation as potential convergence points for non-genetic causes of chronic mental illness.Molecular psychiatry · 2019Review
- Molecular analysis of NPAS3 functional domains and variants.BMC molecular biology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia and other major mental illnesses result from a complex interplay of genetic and environmental factors. We previously identified a mutation in NPAS3 that results in a valine to isoleucine (V304I) amino acid substitution segregating with schizophrenia in a small family. The amino acid change occurs in a potentially critical region for protein function. Furthermore, the same amino acid substitution in proteins related to familial Alzheimer's disease and transthyretin amyloidosis has been associated with protein aggregation. In this study, we demonstrate that NPAS3 is prone to aggregation, and that the V304I mutation in NPAS3 increases this propensity in both bacterial and mammalian expression systems. We also show that NPAS3-V304I reduces soluble endogenous NPAS3, and increases insoluble endogenous NPAS3 and leads to alteration of transcriptional activity. These results suggest that protein aggregation, potentially leading to cell dysfunction via a loss of protein function through sequestration, may contribute to the pathogenesis of schizophrenia and other forms of mental illness. Further exploration of the mechanisms leading to abnormal protein quality control could lead to new therapeutic targets.
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Registered trials
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