NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1 (REV-ERBα)

NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1 (REV-ERBα)

Overview

NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1 (REV-ERBα)

Overview

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">NR1D1 — REV-ERBalpha</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>NR1D1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Nuclear Receptor Subfamily 1 Group D Member 1 (REV-ERBalpha)</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17q11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9973](https://www.ncbi.nlm.nih.gov/gene/9973)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[602437](https://www.omim.org/entry/602437)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000156395</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9UH73](https://www.uniprot.org/uniprot/Q9UH73)</td></tr>
<tr><td><strong>Protein Name</strong></td><td>REV-ERBalpha</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Metabolic disorders</td></tr>
</table>
</div>

NR1D1 (Nuclear Receptor Subfamily 1 Group D Member 1), also known as REV-ERBalpha, is a nuclear receptor protein that functions as a transcriptional repressor. It plays a critical role in regulating circadian rhythm and metabolism. NR1D1 is encoded by the NR1D1 gene located on chromosome 17q11.2. The protein is a member of the nuclear receptor superfamily and acts as a key component of the molecular circadian clock.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>NR1D1</td></tr>
<tr><td><strong>Full Name</strong></td><td>NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17q11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9973](https://www.ncbi.nlm.nih.gov/gene/9973)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[602437](https://www.omim.org/entry/602437)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000156395</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9UH73](https://www.uniprot.org/uniprot/Q9UH73)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Circadian rhythm disorders, metabolic disorders, neurodegeneration</td></tr>
</table>
</div>

Function

NR1D1 (REV-ERBα) is a nuclear receptor and transcriptional repressor that is a key component of the circadian clock. It represses expression of core clock genes and metabolic genes in a circadian manner.

Disease Associations

NR1D1 dysregulation has been implicated in metabolic syndrome and neurodegenerative diseases. REV-ERB agonists show neuroprotective effects in animal models[@sulli2019][@cho2020].

Alzheimer's Disease

• Circadian disruption: AD patients commonly exhibit circadian rhythm disturbances
• Amyloid metabolism: REV-ERB regulates genes involved in amyloid precursor protein (APP) processing
• Neuroinflammation: NR1D1 modulates inflammatory responses in the brain
• Evidence: NR1D1 expression is altered in AD patient brains[@huang2021]

Parkinson's Disease

• Circadian dysfunction: PD patients show disrupted circadian rhythms
• Dopaminergic regulation: REV-ERB affects tyrosine hydroxylase expression
• Mitochondrial function: NR1D1 regulates genes involved in mitochondrial biogenesis
• Evidence: Circadian clock genes show altered expression in PD substantia nigra[@musiek2020]

Metabolic Disorders

• Obesity: REV-ERB agonists reduce adipogenesis
• Diabetes: Metabolic regulation throughNR1D1
• Dyslipidemia: Lipid metabolism effects

Mechanism of Action

Transcriptional Repression

Circadian Rhythm Regulation

• Core component: Part of the transcriptional-translational feedback loop
• Rhythmic expression: NR1D1 peaks during daytime in mice
• Target genes: Controls metabolism, inflammation, and neuronal function

Therapeutic Implications

REV-ERB Agonists

| Application | Mechanism | Status |
|-------------|-----------|--------|
| Neuroprotection | Reduce neuroinflammation | Preclinical[@yin2022] |
| Metabolic benefit | Improve mitochondrial function | Phase I trials |
| Anti-aging | Enhance autophagy | Research |

Drug Development

• Small molecule agonists: SR9009, SR9011
• Combination therapy: With other circadian modulators
• Timing: Circadian timing affects drug efficacy

Expression

Expressed in most tissues with circadian oscillation. In brain, expressed in hypothalamus, [cortex](/brain-regions/cortex), and [hippocampus](/brain-regions/hippocampus).

Key Publications

See Also

• [REV-ERBα Protein](/proteins/nr1d1-protein)
• [Circadian Rhythm and Neurodegeneration](/mechanisms/circadian-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Autophagy Pathway](/mechanisms/autophagy-lysosome-pathway)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)

External Links

• [NCBI Gene: nr1d1](https://www.ncbi.nlm.nih.gov/gene/)
• [PubMed: nr1d1](https://pubmed.ncbi.nlm.nih.gov/?term=nr1d1+neurodegeneration)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving NR1D1 — Nuclear Receptor Subfamily 1 Group D Member 1 (REV-ERBα) discovered through SciDEX knowledge graph analysis: