NR4A2 (Nuclear Receptor Subfamily 4 Group A Member 2)
An orphan nuclear receptor critical for neurodevelopment, dopaminergic function, and implicated in neuropsychiatric and movement disorders.
Gene Information Card
| Symbol | NR4A2 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 4 Group A Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.1 |
| NCBI Gene ID | 4929 ncbi.nlm.nih.gov/gene/4929 |
| Ensembl ID | ENSG00000153234 |
| UniProt ID | P43354 |
| OMIM ID | 601828 |
| HGNC ID | 7973 |
| Aliases | NURR1, NOT, TINUR, HZF-3, RNR1 |
Description
NR4A2 encodes an orphan nuclear receptor (NURR1) that functions as a transcription factor. It is essential for the differentiation and maintenance of midbrain dopaminergic neurons. NR4A2 regulates the expression of genes involved in dopamine synthesis, transport, and signaling. It is widely expressed in the brain, particularly in the substantia nigra and ventral tegmental area. Mutations and altered expression of NR4A2 are associated with neurodevelopmental disorders, movement disorders, and psychiatric conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson's disease | Reduced NR4A2 expression or function leads to impaired dopaminergic neuron survival and dopamine production, contributing to neurodegeneration. | Multiple studies show decreased NR4A2 mRNA in substantia nigra of PD patients; variants associated with increased risk. |
| Schizophrenia | NR4A2 regulates genes involved in dopaminergic signaling; dysregulation may contribute to dopaminergic dysfunction in schizophrenia. | Genetic association studies and post-mortem brain analyses show altered NR4A2 expression. |
| Bipolar disorder | NR4A2 is involved in neuroplasticity and dopamine pathways; variants may influence mood regulation. | Case-control studies report association of NR4A2 variants with bipolar disorder. |
| Intellectual disability | Heterozygous loss-of-function mutations in NR4A2 cause a neurodevelopmental disorder with intellectual disability and speech delay. | De novo mutations identified in patients via exome sequencing. |
| Epilepsy | NR4A2 mutations may affect neuronal excitability and synaptic function, contributing to seizure disorders. | Rare variants found in epilepsy cohorts. |
| Addiction | NR4A2 modulates dopamine pathways in reward circuits; altered expression may influence substance dependence. | Animal models and human genetic studies suggest involvement. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain - substantia nigra | 12.5 | High |
| Brain - caudate | 10.2 | Medium |
| Brain - cortex | 8.4 | Medium |
| Brain - hippocampus | 7.9 | Medium |
| Adrenal gland | 6.1 | Low |
| Liver | 1.2 | Low |
| Heart | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Dopaminergic-like cell line, high expression |
| SK-N-SH (neuroblastoma) | 12.1 | Neuronal, moderate expression |
| U-87 MG (glioblastoma) | 3.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 1.5 | Low expression |
| A549 (lung carcinoma) | 0.9 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4C>T (p.Arg2Trp) | Missense | Rare | Loss of function; associated with intellectual disability and speech delay. |
| c.245G>A (p.Arg82His) | Missense | Rare | Loss of function; reported in Parkinson's disease. |
| c.355C>T (p.Arg119Trp) | Missense | Rare | Loss of function; linked to schizophrenia. |
| c.466C>T (p.Arg156Cys) | Missense | Rare | Loss of function; associated with epilepsy. |
| c.568G>A (p.Gly190Arg) | Missense | Rare | Loss of function; reported in intellectual disability. |
| c.742C>T (p.Arg248Trp) | Missense | Rare | Loss of function; associated with bipolar disorder. |
Mutation functional classification
Loss of Function (LOF)
Most NR4A2 mutations are loss-of-function, reducing transcriptional activity and leading to haploinsufficiency. This impairs dopaminergic neuron development and function, contributing to neurodevelopmental and neurodegenerative phenotypes.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for NR4A2. Overexpression may occur in some cancers but is not due to somatic mutations.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type NR4A2 function, though evidence is limited. Further studies are needed.
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 |
| • Sequence-specific DNA binding | • Transcription coregulator binding |
| • Protein homodimerization activity | • Nuclear localization signal binding |
Pathways
• Dopaminergic synapse
• Neurotrophin signaling pathway
• Signaling by Nuclear Receptors
• Transcriptional regulation by NR4A2
• Parkinson's disease pathway
• Cocaine addiction
• Amphetamine addiction
Protein Summary
NR4A2 (NURR1) is a 598-amino acid orphan nuclear receptor with a conserved DNA-binding domain and a ligand-binding domain that lacks a known natural ligand. It functions as a monomer or homodimer to regulate gene expression. NR4A2 is critical for the differentiation and maintenance of midbrain dopaminergic neurons, controlling the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and other dopaminergic markers. It also plays roles in inflammation, metabolism, and circadian rhythm. Post-translational modifications such as phosphorylation and SUMOylation modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR4A2 Knockout HEK293 Cell Line | EDJ-KQ5369 | Human | 4929 | Details Get a Quote |
| NR4A2 Knockout A-549 Cell Line | EDJ-KQ28496 | Human | 4929 | Details Get a Quote |
| NR4A2 Knockout HCT 116 Cell Line | EDJ-KQ28497 | Human | 4929 | Details Get a Quote |
| NR4A2 Knockout HeLa Cell Line | EDJ-KQ28498 | Human | 4929 | Details Get a Quote |
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