NR5A2 (Nuclear Receptor Subfamily 5 Group A Member 2)
Key regulator of pluripotency, metabolism, and cancer; also known as LRH-1 or hB1F
Gene Information Card
| Symbol | NR5A2 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 5 Group A Member 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 2494 ncbi.nlm.nih.gov/gene/2494 |
| Ensembl ID | ENSG00000116833 |
| UniProt ID | O00482 |
| OMIM ID | 604453 |
| HGNC ID | 7989 |
| Aliases | LRH-1, hB1F, CPF, FTF, B1F, LRH1 |
Description
NR5A2 encodes the liver receptor homolog-1 (LRH-1), an orphan nuclear receptor that regulates gene expression in development, metabolism, and steroidogenesis. It is essential for maintaining pluripotency in embryonic stem cells and plays roles in bile acid synthesis, glucose homeostasis, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Overexpression promotes cell proliferation and migration; acts as a coactivator for β-catenin | PMID: 23431127 |
| Pancreatic ductal adenocarcinoma | Amplification and overexpression drive tumorigenesis via regulation of pluripotency genes | PMID: 23525020 |
| Breast cancer | NR5A2 expression correlates with estrogen receptor status and poor prognosis | PMID: 21804531 |
| Gallbladder cancer | Gain-of-function mutations (e.g., p.Ser441Phe) increase transcriptional activity | PMID: 28112737 |
| Bile acid synthesis disorders | Loss-of-function variants impair CYP7A1 regulation leading to cholestasis | PMID: 12671075 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.8 | Medium |
| Pancreas | 9.5 | Medium |
| Small intestine | 8.2 | Medium |
| Ovary | 6.1 | Low |
| Testis | 4.3 | Low |
| Breast | 3.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma line |
| PANC-1 | 11.0 | Pancreatic cancer line |
| MCF-7 | 6.8 | Breast cancer line |
| NTERA-2 | 9.4 | Embryonal carcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1322C>T (p.Ser441Phe) | Missense | <0.1% in gallbladder cancer | Gain-of-function; increased transcriptional activity |
| c.1061G>A (p.Arg354His) | Missense | Rare | Reduced DNA binding; loss-of-function |
| Amplification (1q32.1) | Copy number gain | ~5% in pancreatic cancer | Overexpression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
p.Arg354His reduces DNA binding and transactivation; linked to impaired bile acid synthesis.
Gain of Function (GOF)
p.Ser441Phe enhances coactivator recruitment and target gene activation; associated with gallbladder cancer.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Bile acid biosynthesis (Reactome:R-HSA-194068)
• Transcriptional regulation of pluripotent stem cells (Reactome:R-HSA-5250941)
• NR5A2 regulates expression of OCT4
• NANOG
• and SOX2
Protein Summary
NR5A2 (LRH-1) is a 541-amino-acid orphan nuclear receptor with a conserved DNA-binding domain and ligand-binding domain. It functions as a monomeric transcription factor, binding to extended half-site sequences. LRH-1 is constitutively active and recruits coactivators such as SRC-1 and PGC-1α. It is critical for maintaining embryonic stem cell pluripotency, regulating bile acid homeostasis, and promoting cell proliferation in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR5A2 Knockout HEK293 Cell Line | EDJ-KQ2634 | Human | 2494 | Details Get a Quote |
| NR5A2 Knockout A-549 Cell Line | EDJ-KQ23385 | Human | 2494 | Details Get a Quote |
| NR5A2 Knockout HCT 116 Cell Line | EDJ-KQ23386 | Human | 2494 | Details Get a Quote |
| NR5A2 Knockout HeLa Cell Line | EDJ-KQ53270 | Human | 2494 | Details Get a Quote |
