BMAL1 (ARNTL) - Core Circadian Clock Regulator
A master transcription factor controlling circadian rhythms and metabolic homeostasis
Gene Information Card
| Symbol | BMAL1 |
|---|---|
| Full Name | Basic Helix-Loop-Helix ARNT Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.3 |
| NCBI Gene ID | 406 ncbi.nlm.nih.gov/gene/406 |
| Ensembl ID | ENSG00000133794 |
| UniProt ID | O00327 |
| OMIM ID | 602550 |
| HGNC ID | 701 |
| Aliases | ARNTL, MOP3, PASD3, bHLHe5, JAP3 |
Description
BMAL1 (ARNTL) encodes a basic helix-loop-helix (bHLH) PAS domain-containing transcription factor that forms a heterodimer with CLOCK or NPAS2 to drive the expression of core clock genes (PER, CRY) and hundreds of downstream targets. It is the essential positive arm of the mammalian circadian oscillator, regulating daily rhythms in behavior, metabolism, immune function, and cell cycle. Loss of BMAL1 leads to arrhythmicity and metabolic, cardiovascular, and neurodegenerative phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Circadian rhythm disorder (familial advanced sleep phase syndrome) | Altered BMAL1/CLOCK transcriptional activity disrupts PER/CRY feedback loops | OMIM #604348 |
| Metabolic syndrome (obesity, type 2 diabetes) | BMAL1 deficiency impairs glucose and lipid metabolism, insulin secretion, and adipogenesis | PMID: 20085714, 20877010 |
| Cancer (breast, colorectal, prostate) | BMAL1 downregulation promotes epithelial-mesenchymal transition, cell proliferation, and genomic instability | COSMIC; PMID: 26772633 |
| Cardiovascular disease (hypertension, myocardial infarction) | Disrupted circadian blood pressure regulation and endothelial function | PMID: 21907143 |
| Neurodegenerative disorders (Parkinson's, Alzheimer's) | BMAL1 loss exacerbates oxidative stress, neuroinflammation, and protein aggregation | PMID: 23178126 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (suprachiasmatic nucleus) | 12.5 | High |
| Liver | 8.3 | Medium |
| Heart | 7.1 | Medium |
| Skeletal muscle | 6.9 | Medium |
| Pancreas | 5.4 | Medium |
| Adipose tissue | 4.8 | Low |
| Lung | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney; high BMAL1 expression |
| HeLa | 7.8 | Cervical carcinoma; moderate expression |
| HepG2 | 6.5 | Hepatocellular carcinoma; moderate expression |
| MCF7 | 4.1 | Breast cancer; low expression |
| A549 | 3.9 | Lung carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119G>A (p.Arg40Gln) | Missense | <0.01% | Reduced transactivation activity; associated with familial advanced sleep phase syndrome |
| c.1483C>T (p.Arg495*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1060_1061insA (p.Thr354Asnfs*12) | Frameshift | <0.01% | Loss of function; premature stop |
| c.1727A>G (p.Tyr576Cys) | Missense | <0.01% | Altered dimerization with CLOCK; reduced transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg495*, p.Thr354Asnfs*12) produce truncated proteins lacking the C-terminal transactivation domain, abolishing transcriptional activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in BMAL1.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg40Gln) may act as dominant-negative by forming nonfunctional heterodimers with CLOCK, reducing target gene expression.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Circadian rhythm (KEGG: hsa04710)
• Circadian entrainment (KEGG: hsa04713)
• Metabolic pathways (KEGG: hsa01100)
• FoxO signaling pathway (KEGG: hsa04068)
• Hedgehog signaling pathway (KEGG: hsa04340)
• p53 signaling pathway (KEGG: hsa04115)
Protein Summary
BMAL1 (ARNTL) is a 626-amino acid transcription factor containing a bHLH domain and two PAS domains (PAS-A and PAS-B) essential for heterodimerization with CLOCK or NPAS2. The BMAL1/CLOCK complex binds E-box elements (CACGTG) in target gene promoters, driving rhythmic expression of PER, CRY, and other clock-controlled genes. Post-translational modifications (phosphorylation, acetylation, SUMOylation) regulate its stability, nuclear localization, and transcriptional activity. BMAL1 also interacts with metabolic sensors (e.g., SIRT1, AMPK) to couple circadian timing with cellular energy status.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BMAL1 Knockout HEK293 Cell Line | EDJ-KQ3060 | Human | 406 | Details Get a Quote |
| BMAL1 Knockout HCT 116 Cell Line | EDJ-KQ22947 | Human | 406 | Details Get a Quote |
| BMAL1 Knockout A-549 Cell Line | EDJ-KQ24321 | Human | 406 | Details Get a Quote |
| BMAL1 Knockout HeLa Cell Line | EDJ-KQ24322 | Human | 406 | Details Get a Quote |
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