Details for: NR0B2

Gene ID: 8431

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NR0B2

Ensembl ID: ENSG00000131910

Description: nuclear receptor subfamily 0 group B member 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestinal epithelial cell CL0002563
    CSI 4.48
    rCSI 4.69%
    PRS 91.21
  • colonocyte CL1000347
    CSI 4.34
    rCSI 6.22%
    PRS 91.5
  • goblet cell CL0000160
    CSI 4.18
    rCSI 3.95%
    PRS 91.2
  • pancreatic acinar cell CL0002064
    CSI 3.52
    rCSI 4.68%
    PRS 95.34
  • mucous neck cell CL0000651
    CSI 2.93
    rCSI 4.23%
    PRS 95.14
  • stem cell CL0000034
    CSI 2.81
    rCSI 2.71%
    PRS 90.19
  • intestine goblet cell CL0019031
    CSI 2.7
    rCSI 2.4%
    PRS 91.22
  • hepatocyte CL0000182
    CSI 2.69
    rCSI 4.81%
    PRS 91.65
  • lung neuroendocrine cell CL1000223
    CSI 2.44
    rCSI 3.61%
    PRS 94.24
  • type L enteroendocrine cell CL0002279
    CSI 2.42
    rCSI 4.53%
    PRS 94.13
  • enteroendocrine cell CL0000164
    CSI 2.32
    rCSI 3.17%
    PRS 91.39
  • periportal region hepatocyte CL0019026
    CSI 2.2
    rCSI 8.55%
    PRS 90.21
  • enterocyte CL0000584
    CSI 2.14
    rCSI 3.46%
    PRS 90.51
  • foveolar cell of stomach CL0002179
    CSI 2.05
    rCSI 4.37%
    PRS 94.48
  • paneth cell CL0000510
    CSI 1.94
    rCSI 2.86%
    PRS 96.68
  • M cell of gut CL0000682
    CSI 1.82
    rCSI 1.94%
    PRS 94.74
  • centrilobular region hepatocyte CL0019029
    CSI 1.73
    rCSI 4.51%
    PRS 89.52
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.52
    rCSI 3.86%
    PRS 88.89
  • pancreatic ductal cell CL0002079
    CSI 1.46
    rCSI 2.85%
    PRS 94.3
  • kidney connecting tubule principal cell CL4030018
    CSI 1.46
    rCSI 10.59%
    PRS 93.07
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.32
    rCSI 3.57%
    PRS 94.64
  • paneth cell of epithelium of small intestine CL1000343
    CSI 0.91
    rCSI 2.55%
    PRS 95.03
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.38
    rCSI 4.04%
    PRS 90.22

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NR0B2](/details-gene/8431), also known as Small Heterodimer Partner (SHP), is an atypical orphan nuclear receptor located on chromosome 1. It functions primarily as a transcriptional corepressor, uniquely lacking a DNA-binding domain and instead regulating gene expression by directly interacting with and inhibiting other nuclear receptors and transcription factors [Link](https://doi.org/10.1126/science.272.5266.1336). **Overall**, expression data reveals that [NR0B2](/details-gene/8431) is a highly significant gene in metabolically active tissues, particularly the gastrointestinal tract and liver. Its highest significance is observed in cells such as [intestinal epithelial cell](/details-cell/CL0002563), [colonocyte](/details-cell/CL1000347), and [hepatocyte](/details-cell/CL0000182), underscoring its central role in regulating cholesterol metabolism, bile acid homeostasis, and glucose sensing. ## Cellular Roles and Expression Landscape The expression profile of [NR0B2](/details-gene/8431) highlights its specialized function in tissues responsible for metabolism, digestion, and nutrient absorption. The most significant expression is found within the epithelial lining of the gastrointestinal tract, with top-ranking cell types including [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 4.48), [colonocyte](/details-cell/CL1000347) (CSI: 4.34), and secretory cells like [goblet cell](/details-cell/CL0000160) (CSI: 4.18). High significance is also noted in key metabolic organs, including the pancreas, specifically in [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 3.52), and the liver, in [hepatocyte](/details-cell/CL0000182) (CSI: 2.69). Further enrichment is observed in various specialized intestinal cells, such as [enteroendocrine cell](/details-cell/CL0000164), [enterocyte](/details-cell/CL0000584), and [Paneth cell](/details-cell/CL0000510). This collective expression pattern strongly suggests that [NR0B2](/details-gene/8431) is a critical regulator of digestive and metabolic processes, integrating nutrient signals to maintain systemic homeostasis. ## Pathways and Molecular Function [NR0B2](/details-gene/8431) functions as a key transcriptional regulator, primarily through its activity as a [transcription corepressor](/QuickGO/term/GO:0003714). It exerts its inhibitory effects by forming heterodimers with a wide range of nuclear receptors, thereby preventing their binding to DNA and subsequent transcriptional activation [Link](https://doi.org/10.1126/science.272.5266.1336). Its molecular function annotations confirm its ability to bind to critical metabolic regulators, including [peroxisome proliferator activated receptor](/QuickGO/term/GO:0042975) (PPAR), [nuclear retinoid x receptor](/QuickGO/term/GO:0046965), and [nuclear thyroid hormone receptor](/QuickGO/term/GO:0046966). This mechanism places it as a central node in the [Nuclear receptor transcription pathway](/content/detail/R-HSA-383280). Consistent with its expression in hepatocytes and intestinal cells, [NR0B2](/details-gene/8431) is deeply involved in [Cholesterol metabolic process](/QuickGO/term/GO:0008203) and [Bile acid and bile salt transport](/QuickGO/term/GO:0015721). It serves as a crucial negative feedback sensor in bile acid synthesis, where high bile acid levels induce its expression, leading to the repression of key synthetic enzymes. Additionally, functional annotations indicate its participation in the [Notch signaling pathway](/QuickGO/term/GO:0007219), [response to glucose](/QuickGO/term/GO:0009749), and [Circadian rhythm](/QuickGO/term/GO:0007623), suggesting it plays a role in integrating metabolic inputs with broader developmental and chronobiological signals [Link](https://doi.org/10.1016/j.abb.2017.08.004). ## Research Directions While the role of [NR0B2](/details-gene/8431) as a metabolic repressor in the liver is well-established, its specific functions in other highly expressive cell types and its potential contribution to disease pathophysiology present key areas for future investigation. **Testable Hypotheses:** 1. Given its high expression in [pancreatic acinar cell](/details-cell/CL0002064) and its annotation in [Positive regulation of insulin secretion](/QuickGO/term/GO:0032024), [NR0B2](/details-gene/8431) may function as a crucial mediator of endocrine-exocrine crosstalk within the pancreas, modulating digestive enzyme synthesis in response to insulin signaling and systemic glucose levels. 2. The high significance of [NR0B2](/details-gene/8431) in secretory intestinal lineages ([goblet cell](/details-cell/CL0000160), [Paneth cell](/details-cell/CL0000510)) and its connection to the [Notch signaling pathway](/QuickGO/term/GO:0007219) suggest a role in regulating intestinal stem cell fate decisions. Dysregulation of [NR0B2](/details-gene/8431) could therefore disrupt the balance of absorptive versus secretory cell differentiation, potentially contributing to the pathogenesis of inflammatory bowel disease or colorectal cancer. **Proposed Experimental Approach:** To test the second hypothesis, one could utilize a murine model with an intestine-specific knockout of [NR0B2](/details-gene/8431). Intestinal organoids derived from these mice and wild-type controls could be cultured and challenged with inflammatory cytokines (e.g., TNF-α) or Notch pathway inhibitors. Single-cell RNA sequencing (scRNA-seq) would then be performed to comprehensively map changes in cell lineage proportions (stem, secretory, absorptive). This approach would clarify whether [NR0B2](/details-gene/8431) is necessary for maintaining intestinal epithelial homeostasis and responding appropriately to inflammatory stress. **Therapeutic Potential:** As a negative regulator of multiple nuclear receptors implicated in metabolic diseases, [NR0B2](/details-gene/8431) represents an attractive therapeutic target. The development of small molecule agonists that enhance or mimic its corepressor function could offer a novel strategy for treating conditions such as non-alcoholic fatty liver disease (NAFLD), cholestasis, and type 2 diabetes. Since loss-of-function mutations are associated with obesity [Link](https://doi.org/10.1073/pnas.98.2.575), a therapeutic strategy based on **activation** of [NR0B2](/details-gene/8431) function, rather than inhibition, appears to be the most promising avenue.

Genular Protein ID: 1651725409

Symbol: NR0B2_HUMAN

Name: Nuclear receptor subfamily 0 group B member 2

UniProtKB Accession Codes:

Q15466 F1D8P5 Q5QP36

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 GO 29 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 13 PDBsum 13 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8650544

Title: An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors.

PubMed ID: 8650544

DOI: 10.1126/science.272.5266.1336

PubMed ID: 9603951

Title: Structure and expression of the orphan nuclear receptor SHP gene.

PubMed ID: 9603951

DOI: 10.1074/jbc.273.23.14398

PubMed ID: 11136233

Title: Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.

PubMed ID: 11136233

DOI: 10.1073/pnas.98.2.575

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14752053

Title: Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD.

PubMed ID: 14752053

DOI: 10.1210/me.2003-0311

PubMed ID: 28797635

Title: Circadian rhythmicity: A functional connection between differentiated embryonic chondrocyte-1 (DEC1) and small heterodimer partner (SHP).

PubMed ID: 28797635

DOI: 10.1016/j.abb.2017.08.004

PubMed ID: 28128295

Title: RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP.

PubMed ID: 28128295

DOI: 10.1038/srep41452

PubMed ID: 15723037

Title: Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP.

PubMed ID: 15723037

DOI: 10.1038/nsmb910

PubMed ID: 21262773

Title: Arginine methylation by PRMT5 at a naturally occurring mutation site is critical for liver metabolic regulation by small heterodimer partner.

PubMed ID: 21262773

DOI: 10.1128/mcb.01212-10

Sequence Information:

  • Length: 257
  • Mass: 28058
  • Checksum: 14BEE2B3FF46154A
  • Sequence:
    • MSTSQPGACP CQGAASRPAI LYALLSSSLK AVPRPRSRCL CRQHRPVQLC APHRTCREAL 
DVLAKTVAFL RNLPSFWQLP PQDQRRLLQG CWGPLFLLGL AQDAVTFEVA EAPVPSILKK 
ILLEEPSSSG GSGQLPDRPQ PSLAAVQWLQ CCLESFWSLE LSPKEYACLK GTILFNPDVP 
GLQAASHIGH LQQEAHWVLC EVLEPWCPAA QGRLTRVLLT ASTLKSIPTS LLGDLFFRPI 
IGDVDIAGLL GDMLLLR