HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NR4A1
nuclear receptor subfamily 4 group A member 1
Chromosome 12 · 12q13.13
NCBI Gene: 3164Ensembl: ENSG00000123358.20HGNC: HGNC:7980UniProt: F5GXF0
308PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of endothelial cell proliferationcell migration involved in sprouting angiogenesisnucleusnuclear speckneurodegenerative diseaseneoplasmbreast cancercancer
✦AI Summary

NR4A1 (nuclear receptor subfamily 4 group A member 1) is a transcription factor that regulates diverse physiological processes through transcriptional control and protein-protein interactions. As a transcription factor, NR4A1 binds to specific DNA sequences to regulate gene expression, including direct binding to the TrkB promoter to enhance transcription and support cognitive function 1, and activation of Wnt4 transcription to promote mesenchymal stem cell osteogenesis 2. The protein also facilitates Foxp3 expression in regulatory T cells, contributing to immune homeostasis 3. Beyond transcriptional activity, NR4A1 functions through direct protein interactions, including binding to CAP1 to regulate platelet activation via cAMP signaling 4. NR4A1 expression is dynamically regulated across various pathological conditions - it decreases with aging in hippocampal neurons correlating with cognitive decline 1, is upregulated during hypercholesterolemia 4, and is suppressed by TGF-β1 during inflammatory bone disorders 2. Clinically, NR4A1 represents a therapeutic target for multiple conditions including cognitive decline, thrombosis, cancer immunotherapy 5, glomerulonephritis 6, and bone regeneration disorders, with specific agonists and degradation strategies showing therapeutic promise across these diverse applications.

Sources cited
1
NR4A1 directly binds to TrkB promoter to enhance transcription and support cognitive function; expression decreases with aging in hippocampal neurons
PMID: 38605605
2
NR4A1 activates Wnt4 transcription to promote mesenchymal stem cell osteogenesis; expression is suppressed by TGF-β1 during inflammatory conditions
PMID: 38429926
3
NR4A1 is required for isoalloLCA-mediated effects on regulatory T cells and Foxp3 expression
PMID: 34416161
4
NR4A1 binds to CAP1 protein and regulates platelet activation via cAMP signaling; expression is upregulated during hypercholesterolemia
PMID: 40035146
5
NR4A1 represents a therapeutic target for cancer immunotherapy
PMID: 38334978
6
NR4A1 serves as a therapeutic target for glomerulonephritis
PMID: 41345104
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.36Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.12Weak
cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.10Suggestive
melanomaOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.09Suggestive
type 2 diabetes mellitusOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
acute respiratory distress syndromeOpen Targets
0.09Suggestive
renal fibrosisOpen Targets
0.09Suggestive
prostate cancerOpen Targets
0.09Suggestive
osteosarcomaOpen Targets
0.09Suggestive
papillary thyroid carcinomaOpen Targets
0.08Suggestive
lymphomaOpen Targets
0.08Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.08Suggestive
cardiac hypertrophyOpen Targets
0.08Suggestive
temporal lobe epilepsyOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NCOA1Protein interaction100%TP53Protein interaction100%JUNProtein interaction100%MAPK3Protein interaction99%FOSProtein interaction99%AKT1Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Lung
20%
Heart
8%
Liver
6%
Bone Marrow
6%
Brain
1%
Gene Interaction Network
Click a node to explore
NR4A1NCOA1TP53JUNMAPK3FOSAKT1
PROTEIN STRUCTURE
Preparing viewer…
PDB4RZF · 1.99 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.51 [0.37–0.71]
RankingsWhere NR4A1 stands among ~20K protein-coding genes
  • #1,118of 20,598
    Most Researched308 · top 10%
  • #5,472of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedNR4A1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.
PMID: 39346541
Theranostics · 2024
1.00
2
Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.
PMID: 38605605
Alzheimers Dement · 2024
0.90
3
NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation.
PMID: 40035146
Circ Res · 2025
0.80
4
Bruceine A protects nuclear receptor 4A1 from ubiquitin-degradation to alleviate mesangial proliferative glomerulonephritis.
PMID: 41345104
Signal Transduct Target Ther · 2025
0.70
5
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors.
PMID: 39151930
J Immunother Cancer · 2024
0.68