ArticlePloS one2014
Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Aryl hydrocarbon receptor nuclear translocator 2: a forgotten per-ARNT-Sim transcription factor.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Multimodal bHLH-PAS DNA binding controls specificity and drives obesity.Nucleic acids research · 2026Article
- Nutrigenomics of Obesity: Integrating Genomics, Epigenetics, and Diet-Microbiome Interactions for Precision Nutrition.Life (Basel, Switzerland) · 2025Review
- Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Astrocyte-derived lactate/NADH alters methamphetamine-induced memory consolidation and retrieval by regulating neuronal synaptic plasticity in the dorsal hippocampus.Brain structure & function · 2022Article
- Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.Scientific reports · 2021Article
- Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.Psychopharmacology · 2020Article
- A viable hypomorphicDisease models & mechanisms · 2018Article
- Expression of the neuroprotective protein aryl hydrocarbon receptor nuclear translocator 2 correlates with neuronal stress and disability in models of multiple sclerosis.Journal of neuroinflammation · 2018Article
- Multiple sequences orchestrate subcellular trafficking of neuronal PAS domain-containing protein 4 (NPAS4).The Journal of biological chemistry · 2018Article
- Article
- miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells.Molecular neurobiology · 2017Article
- Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.Endocrine reviews · 2016Review
- Article
- Npas4: Linking Neuronal Activity to Memory.Trends in neurosciences · 2016Review
- Inducible and reversible lentiviral and Recombination Mediated Cassette Exchange (RMCE) systems for controlling gene expression.PloS one · 2015Article
- Npas4 expression in two experimental models of the barrel cortex plasticity.Neural plasticity · 2015Article
- Decreased expression of neuronal Per-Arnt-Sim domain protein 4 gene in the hippocampus of a post-stroke depression rat model.Experimental and therapeutic medicine · 2014Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal Per-Arnt-Sim homology (PAS) Factor 4 (NPAS4) is a neuronal activity-dependent transcription factor which heterodimerises with ARNT2 to regulate genes involved in inhibitory synapse formation. NPAS4 functions to maintain excitatory/inhibitory balance in neurons, while mouse models have shown it to play roles in memory formation, social interaction and neurodegeneration. NPAS4 has therefore been implicated in a number of neuropsychiatric or neurodegenerative diseases which are underpinned by defects in excitatory/inhibitory balance. Here we have explored a broad set of non-synonymous human variants in NPAS4 and ARNT2 for disruption of NPAS4 function. We found two variants in NPAS4 (F147S and E257K) and two variants in ARNT2 (R46W and R107H) which significantly reduced transcriptional activity of the heterodimer on a luciferase reporter gene. Furthermore, we found that NPAS4.F147S was unable to activate expression of the NPAS4 target gene BDNF due to reduced dimerisation with ARNT2. Homology modelling predicts F147 in NPAS4 to lie at the dimer interface, where it appears to directly contribute to protein/protein interaction. We also found that reduced transcriptional activation by ARNT2 R46W was due to disruption of nuclear localisation. These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation and have potential implications for cognitive phenotypic variation and diseases such as autism, schizophrenia and dementia.
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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 Socratic graph.