NPAS2 (Neuronal PAS Domain Protein 2)
Core circadian clock gene involved in metabolic and behavioral rhythms
Gene Information Card
| Symbol | NPAS2 |
|---|---|
| Full Name | Neuronal PAS Domain Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q11.2 |
| NCBI Gene ID | 4862 ncbi.nlm.nih.gov/gene/4862 |
| Ensembl ID | ENSG00000170485 |
| UniProt ID | Q99743 |
| OMIM ID | 603347 |
| HGNC ID | 7895 |
| Aliases | MOP4, PASD4, bHLHe9 |
Description
NPAS2 encodes a member of the basic helix-loop-helix (bHLH)-PAS transcription factor family. It forms a heterodimer with BMAL1 (ARNTL) to regulate the expression of core clock genes and is essential for the maintenance of circadian rhythms in the forebrain and peripheral tissues. NPAS2 also plays roles in metabolism, DNA damage response, and behavior.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sleep disorders (e.g., advanced sleep phase syndrome) | Altered NPAS2/BMAL1 heterodimer activity disrupts circadian period | PMID: 17054673 |
| Breast cancer | NPAS2 polymorphisms associated with increased risk; altered circadian gene expression in tumors | PMID: 20068074 |
| Prostate cancer | NPAS2 variants linked to risk; circadian disruption promotes tumorigenesis | PMID: 19088176 |
| Bipolar disorder | NPAS2 expression changes in postmortem brain; circadian rhythm dysregulation | PMID: 18568021 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Medium |
| Liver | 4.1 | Low |
| Heart | 3.2 | Low |
| Skeletal muscle | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in circadian studies |
| HEK293 (embryonic kidney) | 6.7 | Moderate expression |
| HepG2 (liver) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1057G>A (p.Ala353Thr) | Missense | <0.01% | Alters PAS domain; potential effect on dimerization |
| c.1465C>T (p.Arg489Trp) | Missense | <0.01% | Located in bHLH domain; may reduce DNA binding |
| rs2305160 (G>A) | SNP | 5-10% (population dependent) | Associated with cancer risk in some studies |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants in bHLH or PAS domains that impair heterodimerization or DNA binding.
Gain of Function (GOF)
Not well documented; some variants may increase transcriptional activity but evidence is limited.
Dominant Negative (DN)
Mutations that disrupt dimerization could act as dominant negative by sequestering BMAL1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Circadian rhythm (KEGG: hsa04710)
• Circadian entrainment (KEGG: hsa04713)
• BMAL1/CLOCK/NPAS2-induced circadian gene expression (Reactome: R-HSA-400253)
Protein Summary
NPAS2 is a 824-amino acid transcription factor containing bHLH and two PAS domains (PAS-A and PAS-B). It heterodimerizes with BMAL1 to bind E-box elements in the promoters of clock-controlled genes. The protein is highly expressed in the brain, particularly in the forebrain, and is involved in regulating circadian rhythms, metabolism, and cellular stress responses. NPAS2 also interacts with the DNA damage response pathway and has been implicated in cancer susceptibility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPAS2 Knockout HEK293 Cell Line | EDJ-KQ5357 | Human | 4862 | Details Get a Quote |
| NPAS2 Knockout A-549 Cell Line | EDJ-KQ28468 | Human | 4862 | Details Get a Quote |
| NPAS2 Knockout HCT 116 Cell Line | EDJ-KQ28469 | Human | 4862 | Details Get a Quote |
| NPAS2 Knockout HeLa Cell Line | EDJ-KQ28470 | Human | 4862 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
