NR4A1 (Nuclear Receptor Subfamily 4 Group A Member 1)
Orphan nuclear receptor involved in cell proliferation, apoptosis, and metabolism; implicated in cancer and inflammatory diseases.
Gene Information Card
| Symbol | NR4A1 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 4 Group A Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.12 |
| NCBI Gene ID | 3164 ncbi.nlm.nih.gov/gene/3164 |
| Ensembl ID | ENSG00000123358 |
| UniProt ID | P22736 |
| OMIM ID | 139139 |
| HGNC ID | 7979 |
| Aliases | Nur77, NGFI-B, TR3, NP10, GFRP1, HMR |
Description
NR4A1 (Nur77) is an orphan nuclear receptor that functions as a transcription factor regulating genes involved in cell cycle, apoptosis, metabolism, and inflammation. It is rapidly induced by various stimuli including growth factors, stress, and inflammatory signals. NR4A1 plays dual roles in cancer, acting as a tumor suppressor or promoter depending on cellular context. It also modulates immune responses and metabolic homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | NR4A1 overexpression promotes cell survival and androgen receptor signaling; knockdown induces apoptosis. | PMID: 23087055, COSMIC |
| Colorectal Cancer | NR4A1 is upregulated and associated with poor prognosis; regulates Wnt/β-catenin pathway. | PMID: 25605247, COSMIC |
| Acute Myeloid Leukemia | NR4A1 acts as a tumor suppressor; loss of expression correlates with leukemogenesis. | PMID: 25778529, ClinVar |
| Rheumatoid Arthritis | NR4A1 modulates inflammatory cytokine production in synovial fibroblasts. | PMID: 20037586 |
| Atherosclerosis | NR4A1 regulates macrophage inflammation and lipid metabolism in vascular plaques. | PMID: 20066033 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 8.2 | Medium |
| Adrenal gland | 12.5 | High |
| Bone marrow | 6.1 | Medium |
| Brain | 4.3 | Low |
| Colon | 7.8 | Medium |
| Heart | 3.9 | Low |
| Kidney | 5.6 | Medium |
| Liver | 9.4 | High |
| Lung | 6.7 | Medium |
| Lymph node | 10.1 | High |
| Muscle | 2.8 | Low |
| Ovary | 7.3 | Medium |
| Pancreas | 5.1 | Medium |
| Prostate | 8.9 | High |
| Skin | 4.5 | Low |
| Small intestine | 6.3 | Medium |
| Spleen | 11.2 | High |
| Stomach | 5.8 | Medium |
| Testis | 7.0 | Medium |
| Thymus | 9.8 | High |
| Thyroid | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 8.5 | Embryonic kidney; moderate expression |
| HeLa | 7.2 | Cervical carcinoma; moderate |
| MCF7 | 9.1 | Breast cancer; high expression |
| PC3 | 10.3 | Prostate cancer; high expression |
| HCT116 | 8.8 | Colorectal cancer; high expression |
| K562 | 6.4 | Leukemia; moderate expression |
| Jurkat | 7.9 | T-cell leukemia; moderate-high |
| HepG2 | 5.3 | Hepatocellular carcinoma; low-moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; functional impact unknown |
| c.145C>T (p.Arg49Trp) | Missense | <0.1% | Reported in COSMIC; potential loss of DNA binding |
| c.632G>A (p.Arg211Gln) | Missense | <0.1% | Found in colorectal cancer; uncertain significance |
| c.1015C>T (p.Arg339Cys) | Missense | <0.1% | Reported in COSMIC; may affect transactivation |
Mutation functional classification
Loss of Function (LOF)
Mutations disrupting DNA-binding domain (e.g., p.Arg49Trp) or N-terminal transactivation domain likely reduce transcriptional activity, contributing to tumor suppression loss in leukemia.
Gain of Function (GOF)
Amplification or overexpression of wild-type NR4A1 in solid tumors (e.g., prostate, colon) can enhance cell survival and proliferation, acting as an oncogene.
Dominant Negative (DN)
Truncating mutations or those affecting dimerization may interfere with wild-type NR4A1 function, though specific dominant-negative variants are not well-characterized in major databases.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NR4A1-mediated signaling (Reactome: R-HSA-383280)
• Retinoic acid receptors (KEGG: hsa03320)
• Apoptosis (KEGG: hsa04210)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Wnt signaling pathway (KEGG: hsa04310)
Protein Summary
NR4A1 (Nur77) is a 598-amino-acid orphan nuclear receptor with an N-terminal transactivation domain, a central DNA-binding domain (two zinc fingers), and a C-terminal ligand-binding domain. It binds as a monomer or homodimer to NGFI-B response elements (NBRE) to regulate target genes. NR4A1 is rapidly induced by diverse signals and shuttles between nucleus and mitochondria to promote apoptosis. Post-translational modifications include phosphorylation, acetylation, and SUMOylation, modulating its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR4A1 Knockout HEK293 Cell Line | EDJ-KQ717 | Human | 3164 | Details Get a Quote |
| NR4A1 Knockout A-549 Cell Line | EDJ-KQ19335 | Human | 3164 | Details Get a Quote |
| NR4A1 Knockout HCT 116 Cell Line | EDJ-KQ19336 | Human | 3164 | Details Get a Quote |
| NR4A1 Knockout HeLa Cell Line | EDJ-KQ19337 | Human | 3164 | Details Get a Quote |
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