NR1D1 (Nuclear Receptor Subfamily 1 Group D Member 1)
A key circadian clock component and transcriptional repressor involved in metabolic and inflammatory regulation.
Gene Information Card
| Symbol | NR1D1 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 1 Group D Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.1 |
| NCBI Gene ID | 9572 ncbi.nlm.nih.gov/gene/9572 |
| Ensembl ID | ENSG00000126368 |
| UniProt ID | Q14994 |
| OMIM ID | 602408 |
| HGNC ID | 7962 |
| Aliases | REV-ERBα, THRA1, ear-1, hRev, Rev-erb-alpha |
Description
NR1D1 (REV-ERBα) encodes a nuclear receptor that functions as a transcriptional repressor. It is a core component of the circadian clock, repressing transcription of target genes such as BMAL1 (ARNTL) and CLOCK. NR1D1 also regulates genes involved in lipid and glucose metabolism, inflammation, and cell cycle. Its activity is modulated by heme binding, and it is implicated in metabolic disorders, inflammatory diseases, and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Metabolic syndrome | Dysregulation of NR1D1 alters lipid and glucose homeostasis via repression of metabolic genes (e.g., SREBP1c, PEPCK) | PMID: 23603847 |
| Type 2 diabetes | NR1D1 disruption impairs insulin secretion and glucose tolerance | PMID: 26951783 |
| Breast cancer | NR1D1 overexpression correlates with poor prognosis; represses tumor suppressor genes | PMID: 27323850 |
| Colorectal cancer | NR1D1 loss promotes proliferation via MYC and cell cycle gene activation | PMID: 31073040 |
| Inflammatory bowel disease | NR1D1 deficiency exacerbates colitis via NF-κB pathway activation | PMID: 29018167 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 9.8 | Medium |
| Skeletal muscle | 8.2 | Medium |
| Brain (cortex) | 6.1 | Low |
| Heart | 7.4 | Medium |
| Pancreas | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| MCF7 | 11.0 | Breast cancer cell line |
| A549 | 9.5 | Lung adenocarcinoma cell line |
| HEK293 | 7.8 | Embryonic kidney cell line |
| K562 | 6.3 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Pro34Leu) | Missense | <0.01% | Altered heme binding; reduced repressor activity (ClinVar) |
| c.457G>A (p.Gly153Arg) | Missense | <0.01% | Unknown functional impact (ClinVar) |
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Premature truncation; loss of function (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that impair DNA binding, heme binding, or transcriptional repression (e.g., p.Pro34Leu).
Gain of Function (GOF)
Not well documented; some variants may increase repressor activity but no confirmed examples.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003707 (nuclear receptor activity) | • GO:0004879 (nuclear receptor transcription coactivator activity) |
| • GO:0005515 (protein binding) | • GO:0005634 (nucleus) |
| • GO:0007623 (circadian rhythm) | • GO:0045892 (negative regulation of transcription |
| • DNA-templated) | • GO:0006357 (regulation of transcription by RNA polymerase II) |
Pathways
• Circadian rhythm (KEGG hsa04710)
• Nuclear receptor signaling (Reactome R-HSA-383280)
• Metabolism of lipids (Reactome R-HSA-556833)
Protein Summary
NR1D1 (REV-ERBα) is a 614-amino-acid nuclear receptor with an N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It binds as a monomer or homodimer to RORE elements in target gene promoters, recruiting corepressors such as NCOR1 and HDAC3 to repress transcription. Heme acts as a ligand, modulating its activity. The protein is central to circadian clock regulation and metabolic homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR1D1 Knockout HEK293 Cell Line | EDJ-KQ2307 | Human | 9572 | Details Get a Quote |
| NR1D1 Knockout HeLa Cell Line | EDJ-KQ21359 | Human | 9572 | Details Get a Quote |
| NR1D1 Knockout A-549 Cell Line | EDJ-KQ22686 | Human | 9572 | Details Get a Quote |
| NR1D1 Knockout HCT 116 Cell Line | EDJ-KQ22687 | Human | 9572 | Details Get a Quote |
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