NR4A3 (Nuclear Receptor Subfamily 4 Group A Member 3)
Orphan nuclear receptor involved in cell proliferation, differentiation, and apoptosis; recurrently rearranged in soft tissue tumors.
Gene Information Card
| Symbol | NR4A3 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 4 Group A Member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q22.33 |
| NCBI Gene ID | 8013 ncbi.nlm.nih.gov/gene/8013 |
| Ensembl ID | ENSG00000119508 |
| UniProt ID | Q92570 |
| OMIM ID | 600542 |
| HGNC ID | 7981 |
| Aliases | NOR1, CHN, CSMF, TEC |
Description
NR4A3 (Nuclear Receptor Subfamily 4 Group A Member 3), also known as NOR1, is an orphan nuclear receptor that functions as a transcription factor. It is involved in the regulation of cell proliferation, differentiation, apoptosis, and inflammation. NR4A3 is expressed in various tissues and plays a role in the central nervous system, immune response, and metabolism. Chromosomal rearrangements involving NR4A3 are recurrent in certain soft tissue tumors, particularly extraskeletal myxoid chondrosarcoma, where it is fused to various partner genes, leading to oncogenic transformation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Extraskeletal Myxoid Chondrosarcoma | Recurrent chromosomal translocations fuse NR4A3 with EWSR1, TAF15, or TCF12, creating chimeric transcription factors that drive tumorigenesis. | COSMIC; OMIM |
| Acute Myeloid Leukemia | NR4A3 expression is downregulated in a subset of AML cases, suggesting a tumor suppressor role. | NCBI Gene; PubMed (via OMIM) |
| Prostate Cancer | NR4A3 expression is altered in prostate cancer, potentially influencing tumor progression. | COSMIC; PubMed (via OMIM) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.7 | Low |
| Liver | 3.2 | Low |
| Skeletal Muscle | 5.1 | Low |
| Kidney | 6.4 | Low |
| Testis | 15.3 | Medium |
| Thyroid | 10.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | 18.5 | Chronic myelogenous leukemia cell line |
| HeLa | 7.3 | Cervical adenocarcinoma cell line |
| A549 | 5.8 | Lung carcinoma cell line |
| MCF7 | 9.1 | Breast adenocarcinoma cell line |
| HepG2 | 4.2 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| EWSR1-NR4A3 fusion | Chromosomal translocation | Recurrent in extraskeletal myxoid chondrosarcoma | Oncogenic fusion protein |
| TAF15-NR4A3 fusion | Chromosomal translocation | Rare | Oncogenic fusion protein |
| TCF12-NR4A3 fusion | Chromosomal translocation | Rare | Oncogenic fusion protein |
| Missense mutations | Point mutation | Low frequency in various cancers | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NR4A3 are not well characterized; however, reduced expression is observed in some cancers, suggesting a tumor suppressor role.
Gain of Function (GOF)
Gain-of-function is primarily due to gene fusions (e.g., EWSR1-NR4A3) that create chimeric proteins with aberrant transcriptional activity.
Dominant Negative (DN)
Dominant-negative effects are not well documented for NR4A3 mutations.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • steroid hormone receptor activity | • zinc ion binding |
| • nucleus | • cytoplasm |
| • regulation of transcription by RNA polymerase II | • cell differentiation |
| • apoptotic process | • inflammatory response |
Pathways
• Nuclear receptor transcription pathway
• NR4A signaling in cancer
• Apoptosis regulation
Protein Summary
NR4A3 is a 626-amino acid protein with a molecular weight of approximately 68 kDa. It contains a conserved DNA-binding domain with two zinc fingers and a ligand-binding domain, although no natural ligand has been identified (orphan receptor). The protein localizes to the nucleus and acts as a transcription factor, regulating target genes involved in cell cycle, apoptosis, and differentiation. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR4A3 Knockout HEK293 Cell Line | EDJ-KQ6158 | Human | 8013 | Details Get a Quote |
| NR4A3 Knockout A-549 Cell Line | EDJ-KQ29967 | Human | 8013 | Details Get a Quote |
| NR4A3 Knockout HeLa Cell Line | EDJ-KQ29968 | Human | 8013 | Details Get a Quote |
| NR4A3 Knockout HCT 116 Cell Line | EDJ-KQ71773 | Human | 8013 | Details Get a Quote |
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