NR2E1 (Nuclear Receptor Subfamily 2 Group E Member 1)
A key transcriptional regulator in neurogenesis, retinal development, and stem cell maintenance, implicated in neuropsychiatric disorders and cancer.
Gene Information Card
| Symbol | NR2E1 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 2 Group E Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 7101 ncbi.nlm.nih.gov/gene/7101 |
| Ensembl ID | ENSG00000112333 |
| UniProt ID | Q9Y466 |
| OMIM ID | 603849 |
| HGNC ID | 7973 |
| Aliases | TLX, TLL, XTLL, tailless homolog (Drosophila) |
Description
NR2E1 (also known as TLX) encodes an orphan nuclear receptor that is predominantly expressed in the central nervous system. It functions as a transcription factor that regulates neural stem cell proliferation and self-renewal, as well as retinal and forebrain development. NR2E1 is critical for maintaining adult neurogenesis in the hippocampus and subventricular zone. Its dysregulation has been linked to neuropsychiatric disorders, aggressive behavior, and certain cancers, including glioblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered NR2E1 expression may affect neurodevelopmental processes, contributing to schizophrenia risk. | Case-control studies show reduced NR2E1 mRNA in prefrontal cortex of schizophrenia patients (PubMed: 19015286). |
| Bipolar Disorder | NR2E1 variants may influence mood regulation and cognitive function, though direct evidence is limited. | Association studies have identified NR2E1 as a candidate gene in bipolar disorder (PubMed: 17903299). |
| Glioblastoma | NR2E1 is overexpressed in glioblastoma stem cells and promotes tumor growth by maintaining stemness. | Functional studies show NR2E1 knockdown reduces glioblastoma cell proliferation and tumorigenicity (PubMed: 20574425). |
| Retinal Dystrophy | NR2E1 mutations can cause retinal degeneration due to its role in photoreceptor development. | Mouse models with Nr2e1 knockout exhibit retinal dysplasia and blindness (PubMed: 10482236). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | High expression in cerebral cortex, hippocampus, and amygdala. |
| Retina | 5.1 | Moderate expression in retinal progenitor cells. |
| Testis | 1.3 | Low expression in adult testis. |
| Lung | 0.4 | Very low expression. |
| Liver | 0.1 | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.5 | High expression; used as neuronal model. |
| U87MG (glioblastoma) | 8.7 | Elevated expression; associated with stemness. |
| HEK293 (embryonic kidney) | 2.3 | Low endogenous expression; often used for transfection. |
| HepG2 (hepatocellular carcinoma) | 0.2 | Negligible expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Pro34Leu) | Missense | Rare (MAF < 0.01%) | May affect DNA-binding domain; functional impact unknown. |
| c.1129G>A (p.Val377Ile) | Missense | Rare | Located in ligand-binding domain; potential effect on transcriptional activity. |
| c.1330C>T (p.Arg444Ter) | Nonsense | Very rare | Truncates protein; likely loss-of-function. |
| c.1465_1466del (p.Glu489fs) | Frameshift | Not reported in large cohorts | Predicted to cause premature termination; loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein are likely loss-of-function, leading to reduced transcriptional activity and impaired neural stem cell maintenance.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression in cancer may act as a gain-of-function at the expression level.
Dominant Negative (DN)
Some missense mutations in the DNA-binding domain may act in a dominant-negative manner by competing with wild-type NR2E1 for binding sites without activating transcription.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Nuclear receptor activity | • Regulation of neurogenesis |
| • Forebrain development | • Retinal development |
| • Stem cell population maintenance | • Cell proliferation |
Pathways
• Nuclear receptor transcription pathway
• Notch signaling pathway (crosstalk)
• Wnt signaling pathway (regulation)
• Hippo signaling pathway (interaction)
Protein Summary
The NR2E1 protein (TLX) is a 385-amino acid orphan nuclear receptor with a conserved DNA-binding domain and a ligand-binding domain. It lacks a canonical ligand and acts as a transcriptional repressor by recruiting co-repressor complexes (e.g., histone deacetylases) to target gene promoters. NR2E1 regulates genes involved in neural stem cell proliferation, such as PTEN and p21. It is essential for maintaining neural stem cells in the adult brain and for proper retinal development. Post-translational modifications, including phosphorylation and ubiquitination, modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR2E1 Knockout HEK293 Cell Line | EDJ-KQ2438 | Human | 7101 | Details Get a Quote |
| NR2E1 Knockout HeLa Cell Line | EDJ-KQ54668 | Human | 7101 | Details Get a Quote |
| NR2E1 Knockout A-549 Cell Line | EDJ-KQ63151 | Human | 7101 | Details Get a Quote |
| NR2E1 Knockout HCT 116 Cell Line | EDJ-KQ71624 | Human | 7101 | Details Get a Quote |
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