NPAS4
Neuronal PAS Domain Protein 4
Gene Information Card
| Symbol | NPAS4 |
|---|---|
| Full Name | Neuronal PAS Domain Protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 266743 ncbi.nlm.nih.gov/gene/266743 |
| Ensembl ID | ENSG00000166165 |
| UniProt ID | Q8IUM7 |
| OMIM ID | 608554 |
| HGNC ID | 16229 |
| Aliases | bHLHe79, PASD10, NXF |
Description
NPAS4 (Neuronal PAS Domain Protein 4) is a basic helix-loop-helix (bHLH) transcription factor that belongs to the PAS domain family. It is primarily expressed in the brain and plays a critical role in activity-dependent gene regulation, particularly in response to neuronal excitation. NPAS4 regulates the expression of genes involved in synaptic plasticity, neuroprotection, and inhibitory synapse development. It forms heterodimers with ARNT (aryl hydrocarbon receptor nuclear translocator) to bind E-box response elements in target gene promoters.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorders | Altered NPAS4 expression may disrupt activity-dependent gene programs critical for synapse formation and plasticity, contributing to conditions such as autism spectrum disorder and intellectual disability. | ClinVar, PubMed |
| Schizophrenia | NPAS4 dysregulation has been implicated in impaired inhibitory neuron function and synaptic imbalance, potentially contributing to schizophrenia pathophysiology. | PubMed, OMIM |
| Epilepsy | NPAS4 is rapidly induced by seizures and may modulate excitatory/inhibitory balance; altered expression is observed in epileptic brain tissue. | PubMed, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (hippocampus) | 15.2 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Testis | 1.2 | Not detected |
| Heart | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal-like expression |
| U-87 MG (glioblastoma) | 3.4 | Low expression |
| HEK293 (embryonic kidney) | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Unknown; predicted damaging by in silico tools |
| c.457G>A (p.Gly153Ser) | Missense | <0.01% | Unknown; likely benign |
| c.789_790insA | Frameshift | <0.01% | Loss of function predicted |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate the bHLH or PAS domains are predicted to abolish DNA binding and transcriptional activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported in NPAS4.
Dominant Negative (DN)
Missense mutations in the dimerization domain may interfere with heterodimer formation with ARNT, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Activity-dependent gene expression in neurons
• Synaptic plasticity and memory
• Circadian rhythm (via PAS domain interactions)
Protein Summary
NPAS4 is a 802-amino acid transcription factor containing a bHLH domain and two PAS domains (PAS-A and PAS-B). It is rapidly induced by neuronal activity, including membrane depolarization and calcium influx. NPAS4 heterodimerizes with ARNT and binds to E-box sequences (CACGTG) to regulate genes involved in inhibitory synapse formation, neuroprotection, and homeostatic plasticity. The protein is predominantly nuclear and is expressed in excitatory and inhibitory neurons. NPAS4 knockout mice exhibit deficits in fear memory and synaptic scaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPAS4 Knockout HEK293 Cell Line | EDJ-KQ11911 | Human | 266743 | Details Get a Quote |
| NPAS4 Knockout HeLa Cell Line | EDJ-KQ40388 | Human | 266743 | Details Get a Quote |
| NPAS4 Knockout A-549 Cell Line | EDJ-KQ67818 | Human | 266743 | Details Get a Quote |
| NPAS4 Knockout HCT 116 Cell Line | EDJ-KQ76203 | Human | 266743 | Details Get a Quote |
