NR0B2 (Nuclear Receptor Subfamily 0 Group B Member 2)
Orphan nuclear receptor involved in metabolic regulation and bile acid homeostasis
Gene Information Card
| Symbol | NR0B2 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 0 Group B Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 8431 ncbi.nlm.nih.gov/gene/8431 |
| Ensembl ID | ENSG00000131979 |
| UniProt ID | Q15466 |
| OMIM ID | 604630 |
| HGNC ID | 7961 |
| Aliases | SHP, SHP1 |
Description
NR0B2 encodes the small heterodimer partner (SHP), an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. SHP functions as a transcriptional repressor by interacting with other nuclear receptors, including LRH-1, HNF4A, and LXR, thereby regulating bile acid synthesis, glucose metabolism, and lipid homeostasis. It is predominantly expressed in the liver, pancreas, and intestine.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | SHP represses bile acid synthesis; loss-of-function variants may alter energy expenditure and fat storage | PMID: 11889211 |
| Type 2 diabetes | SHP modulates hepatic gluconeogenesis via HNF4A interaction; variants may impair glucose regulation | PMID: 15601839 |
| Gallstone disease | SHP regulates bile acid pool size; reduced SHP activity can increase cholesterol saturation | PMID: 12671058 |
| Hepatocellular carcinoma | SHP inhibits cell proliferation; downregulation observed in liver tumors | PMID: 17938204 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Pancreas | 8.3 | Medium |
| Small intestine | 6.1 | Medium |
| Adipose tissue | 2.4 | Low |
| Kidney | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| Caco-2 | 7.8 | Colorectal adenocarcinoma cell line |
| PANC-1 | 4.5 | Pancreatic ductal adenocarcinoma cell line |
| HEK293 | 1.2 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.553G>A (p.Gly185Arg) | Missense | <0.01% | Reduced repressor activity; associated with obesity |
| c.109G>A (p.Gly37Ser) | Missense | <0.01% | Impaired interaction with HNF4A; linked to type 2 diabetes |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; rare in population |
Mutation functional classification
Loss of Function (LOF)
p.Gly185Arg and p.Met1Val reduce or abolish SHP repressor function, leading to dysregulated bile acid and glucose metabolism.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not described for NR0B2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Bile acid biosynthesis (Reactome: R-HSA-194068)
• NR1H2 and NR1H3-mediated signaling (Reactome: R-HSA-9029569)
• Regulation of lipid metabolism by PPARalpha (Reactome: R-HSA-400206)
Protein Summary
The small heterodimer partner (SHP) is a 257-amino acid orphan nuclear receptor that lacks a DNA-binding domain. It acts as a transcriptional repressor by heterodimerizing with other nuclear receptors, such as LRH-1 and HNF4A, and recruiting corepressors. SHP is a key regulator of bile acid homeostasis, glucose metabolism, and cell proliferation. Its expression is induced by bile acids via FXR, forming a negative feedback loop.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR0B2 Knockout HEK293 Cell Line | EDJ-KQ6237 | Human | 8431 | Details Get a Quote |
| NR0B2 Knockout HeLa Cell Line | EDJ-KQ54905 | Human | 8431 | Details Get a Quote |
| NR0B2 Knockout A-549 Cell Line | EDJ-KQ63392 | Human | 8431 | Details Get a Quote |
| NR0B2 Knockout HCT 116 Cell Line | EDJ-KQ71860 | Human | 8431 | Details Get a Quote |
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