ArticleMolecular psychiatry2018
Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- The association between rs12807809 polymorphism in neurogranin gene and risk of schizophrenia: A meta-analysis.Medicine · 2019Pooled it
- Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons.Science advances · 2026Article
- Genome-wide CRISPR screening identifies Annexin A1 as a facilitator of porcine astrovirus entry.PLoS pathogens · 2026Article
- Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.Schizophrenia bulletin · 2024Article
- ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome.BMC psychiatry · 2024Article
- Schizophrenia risk proteins ZNF804A and NT5C2 interact in cortical neurons.The European journal of neuroscience · 2024Article
- Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review.Briefings in bioinformatics · 2024Review
- Polymorphism in the ZNF804A Gene and Variation in DBiological psychiatry. Cognitive neuroscience and neuroimaging · 2023Article
- A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).European archives of psychiatry and clinical neuroscience · 2022Article
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- Zinc in Cognitive Impairment and Aging.Biomolecules · 2022Review
- The importance of fasciculation and elongation protein zeta-1 in neural circuit establishment and neurological disorders.Neural regeneration research · 2022Review
- Association between rs1344706 Polymorphism in the ZNF804A Gene and the Risk for Schizophrenia.Iranian journal of psychiatry · 2021Article
- A comprehensive analysis of copy number variation in a Turkish dementia cohort.Human genomics · 2021Article
- rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics.Experimental and therapeutic medicine · 2021Article
- ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors.Molecular psychiatry · 2021Article
- Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development.Molecular brain · 2021Article
- Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.Brain communications · 2021Article
- Review
- Schizophrenia‑associated microRNA‑148b‑3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells.Molecular medicine reports · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result. ZNF804A co-fractionates with translational machinery and modulates the translational efficiency as well as the mTOR pathway. The ribosomal protein RPSA interacts with ZNF804A and rescues the migration and translational defects caused by ZNF804A knockdown. RNA immunoprecipitation-RNAseq (RIP-Seq) identified transcripts bound to ZFP804A. Consistently, ZFP804A associates with many short transcripts involved in translational and mitochondrial regulation. Moreover, among the transcripts associated with ZFP804A, a SZ risk gene, neurogranin (NRGN), is one of ZFP804A targets. Interestingly, downregulation of ZFP804A decreases NRGN expression and overexpression of NRGN can ameliorate ZFP804A-mediated migration defect. To verify the downstream targets of ZNF804A, a Duolink in situ interaction assay confirmed genes from our RIP-Seq data as the ZNF804A targets. Thus, our work uncovered a novel mechanistic link of a SZ risk gene to neurodevelopment and translational control. The interactome-driven approach here is an effective way for translating genome-wide association findings into novel biological insights of human diseases.
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