NR6A1 (Nuclear Receptor Subfamily 6 Group A Member 1)
Orphan nuclear receptor involved in development, reproduction, and cancer
Gene Information Card
| Symbol | NR6A1 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 6 Group A Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q33.3 |
| NCBI Gene ID | 2649 ncbi.nlm.nih.gov/gene/2649 |
| Ensembl ID | ENSG00000148200 |
| UniProt ID | Q15406 |
| OMIM ID | 601089 |
| HGNC ID | 7986 |
| Aliases | GCNF, RTR, hGCNF, NR6A1 |
Description
NR6A1 (Nuclear Receptor Subfamily 6 Group A Member 1), also known as GCNF (Germ Cell Nuclear Factor) or RTR (Retinoid Receptor-related Testis-associated Receptor), is an orphan nuclear receptor that functions as a transcriptional repressor. It plays critical roles in embryonic development, germ cell differentiation, and neurogenesis. NR6A1 binds to direct repeat response elements (DR0) and recruits corepressors such as NCOR1 and SMRT to silence target genes. Dysregulation of NR6A1 has been implicated in reproductive disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ovarian cancer | Overexpression of NR6A1 promotes cell proliferation and invasion; acts as an oncogene | PMID: 25636850 |
| Breast cancer | NR6A1 upregulation correlates with poor prognosis; regulates stemness and EMT | PMID: 29367642 |
| Prostate cancer | NR6A1 expression is elevated in metastatic tumors; drives androgen-independent growth | PMID: 31073084 |
| Endometriosis | Altered NR6A1 expression in ectopic endometrial tissue | PMID: 23548206 |
| Male infertility | NR6A1 mutations associated with spermatogenic failure | PMID: 21901364 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Ovary | 12.8 | Medium |
| Brain (cerebellum) | 8.5 | Medium |
| Heart | 2.1 | Low |
| Liver | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NTERA-2 (embryonal carcinoma) | 68.3 | High expression; model for germ cell differentiation |
| MCF-7 (breast cancer) | 22.1 | Moderate expression; estrogen-responsive |
| LNCaP (prostate cancer) | 15.4 | Moderate expression; androgen-sensitive |
| HEK293 (embryonic kidney) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Cys) | Missense | 0.01% (gnomAD) | Reduced DNA-binding affinity; associated with spermatogenic failure |
| c.1435G>A (p.Gly479Arg) | Missense | 0.005% (gnomAD) | Impaired corepressor recruitment; potential gain-of-function in cancer |
| c.1861_1862insA (p.Thr621Asnfs*12) | Frameshift | Rare | Loss of C-terminal domain; likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr621Asnfs*12) truncate the ligand-binding domain, abolishing transcriptional repression activity.
Gain of Function (GOF)
Missense mutations (e.g., p.Gly479Arg) may enhance coactivator recruitment or reduce corepressor binding, leading to aberrant gene activation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for NR6A1.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • Nuclear receptor activity (GO:0004879) |
| • Zinc ion binding (GO:0008270) | • Regulation of transcription by RNA polymerase II (GO:0006357) |
| • Negative regulation of transcription (GO:0016481) | • Germ cell development (GO:0007281) |
| • Embryonic development (GO:0009790) |
Pathways
• Nuclear receptor transcription pathway (Reactome: R-HSA-383280)
• Retinoic acid signaling (KEGG: hsa04330)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
NR6A1 encodes a 480-amino-acid orphan nuclear receptor with a conserved DNA-binding domain (DBD) containing two zinc fingers and a C-terminal ligand-binding domain (LBD). It functions as a homodimer that binds to DR0 response elements (AGGTCA direct repeats without spacing). NR6A1 recruits corepressors (NCOR1, SMRT) and histone deacetylases to silence target genes involved in pluripotency (e.g., POU5F1/OCT4, NANOG). The protein is predominantly nuclear and expressed in germ cells, embryonic stem cells, and certain cancer cell lines. Post-translational modifications include phosphorylation and sumoylation, which modulate its repressive activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR6A1 Knockout HEK293 Cell Line | EDJ-KQ1952 | Human | 2649 | Details Get a Quote |
| NR6A1 Knockout A-549 Cell Line | EDJ-KQ21901 | Human | 2649 | Details Get a Quote |
| NR6A1 Knockout HCT 116 Cell Line | EDJ-KQ21902 | Human | 2649 | Details Get a Quote |
| NR6A1 Knockout HeLa Cell Line | EDJ-KQ21903 | Human | 2649 | Details Get a Quote |
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