The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear ... See more...

Aliases for NR0B2 Gene

Aliases for NR0B2 Gene

  • Nuclear Receptor Subfamily 0 Group B Member 2 2 3 4 5
  • SHP 2 3 4
  • Orphan Nuclear Receptor SHP 3 4
  • Small Heterodimer Partner 3 4
  • Nuclear Receptor Subfamily 0, Group B, Member 2 2
  • Nuclear Receptor SHP 3
  • NR0B2 5
  • SHP1 3

External Ids for NR0B2 Gene

Previous GeneCards Identifiers for NR0B2 Gene

  • GC01P028351
  • GC01M026270
  • GC01M026471
  • GC01M026842
  • GC01M027110
  • GC01M027237
  • GC01M025491

Summaries for NR0B2 Gene

Entrez Gene Summary for NR0B2 Gene

  • The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function. [provided by RefSeq, Jul 2008]

GeneCards Summary for NR0B2 Gene

NR0B2 (Nuclear Receptor Subfamily 0 Group B Member 2) is a Protein Coding gene. Diseases associated with NR0B2 include Body Mass Index Quantitative Trait Locus 11 and Obesity Due To Melanocortin 4 Receptor Deficiency. Among its related pathways are Androgen receptor signaling pathway and Farnesoid X Receptor Pathway. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription factor binding. An important paralog of this gene is NR0B1.

UniProtKB/Swiss-Prot Summary for NR0B2 Gene

  • Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways (By similarity). Specifically inhibits transactivation of the nuclear receptor with which it interacts (By similarity). Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1 (PubMed:14752053). Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism (By similarity). Regulates the circadian expression of cytochrome P450 (CYP) enzymes (By similarity). Represses: NR5A2 and HNF4A to down-regulate CYP2C38, NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2, CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and CYP4A14 (By similarity).

Gene Wiki entry for NR0B2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NR0B2 Gene

Genomics for NR0B2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NR0B2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NR0B2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NR0B2

Top Transcription factor binding sites by QIAGEN in the NR0B2 gene promoter:
  • AhR
  • Arnt
  • C/EBPalpha
  • CHOP-10
  • Lmo2
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT3

Genomic Locations for NR0B2 Gene

Latest Assembly
chr1:26,911,489-26,914,110
(GRCh38/hg38)
Size:
2,622 bases
Orientation:
Minus strand

Previous Assembly
chr1:27,237,980-27,240,466
(GRCh37/hg19 by Entrez Gene)
Size:
2,487 bases
Orientation:
Minus strand

chr1:27,237,980-27,240,457
(GRCh37/hg19 by Ensembl)
Size:
2,478 bases
Orientation:
Minus strand

Genomic View for NR0B2 Gene

Genes around NR0B2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NR0B2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NR0B2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NR0B2 Gene

Proteins for NR0B2 Gene

  • Protein details for NR0B2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15466-NR0B2_HUMAN
    Recommended name:
    Nuclear receptor subfamily 0 group B member 2
    Protein Accession:
    Q15466
    Secondary Accessions:
    • F1D8P5
    • Q5QP36

    Protein attributes for NR0B2 Gene

    Size:
    257 amino acids
    Molecular mass:
    28058 Da
    Quaternary structure:
    • Interacts (via N-terminus) with NEUROD1 (via N-terminus and C-terminus) (PubMed:14752053). Interacts with ID2 (PubMed:14752053). Interacts with RORG, NFIL3, NR1D1 and BHLHE41 (By similarity). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (PubMed:14752053). Interacts with RARA, RXRA, THRB, NR5A1, NR5A2, NR1I3, PPARA, PPARG and EID1 (By similarity). Interacts with HNF4A; the resulting heterodimer is transcriptionnally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2/SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).

    Three dimensional structures from OCA and Proteopedia for NR0B2 Gene

neXtProt entry for NR0B2 Gene

Post-translational modifications for NR0B2 Gene

  • Arginine methylation by PRMT5 enhances repression activity of metabolic genes in liver in response to bile acid signaling, by increasing interaction with cofactors.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NR0B2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NR0B2 Gene

Domains & Families for NR0B2 Gene

Gene Families for NR0B2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Nuclear receptors
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NR0B2 Gene

Suggested Antigen Peptide Sequences for NR0B2 Gene

GenScript: Design optimal peptide antigens:
  • Nuclear receptor subfamily 0, group B, member 2 (F1D8P5_HUMAN)
  • Small heterodimer partner (NR0B2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q15466

UniProtKB/Swiss-Prot:

NR0B2_HUMAN :
  • Belongs to the nuclear hormone receptor family. NR0 subfamily.
Family:
  • Belongs to the nuclear hormone receptor family. NR0 subfamily.
genes like me logo Genes that share domains with NR0B2: view

Function for NR0B2 Gene

Molecular function for NR0B2 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways (By similarity). Specifically inhibits transactivation of the nuclear receptor with which it interacts (By similarity). Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1 (PubMed:14752053). Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism (By similarity). Regulates the circadian expression of cytochrome P450 (CYP) enzymes (By similarity). Represses: NR5A2 and HNF4A to down-regulate CYP2C38, NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2, CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and CYP4A14 (By similarity).
GENATLAS Biochemistry:
orphan nuclear (steroid/thyroid/retinoid) receptor,subfamily 0,group B,member 2,orphan specifically expressed in fetal liver and adrenal gland,adult spleen and small intestine,heterodimerizing with many members of receptor superfamily including RARs,RRXs,small heterodimer partner interacting with PPARx,potential negative regulator of receptor dependent signaling pathways

Phenotypes From GWAS Catalog for NR0B2 Gene

Gene Ontology (GO) - Molecular Function for NR0B2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003714 transcription corepressor activity TAS 11030331
GO:0005515 protein binding IPI 14752053
GO:0008134 transcription factor binding IEA,IBA 21873635
GO:0019904 protein domain specific binding IPI 17686645
GO:0042803 protein homodimerization activity IPI 16709599
genes like me logo Genes that share ontologies with NR0B2: view
genes like me logo Genes that share phenotypes with NR0B2: view

Human Phenotype Ontology for NR0B2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NR0B2 Gene

MGI Knock Outs for NR0B2:

Animal Models for research

  • Taconic Biosciences Mouse Models for NR0B2

miRNA for NR0B2 Gene

miRTarBase miRNAs that target NR0B2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR0B2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NR0B2 Gene

Localization for NR0B2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR0B2 Gene

Nucleus. Cytoplasm. Note=Colocalizes with NEUROD1 in the nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NR0B2 gene
Compartment Confidence
nucleus 5
plasma membrane 3
extracellular 3
mitochondrion 3
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for NR0B2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IDA,ISA --
GO:0005634 nucleus IBA,IDA 14752053
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA,IDA 14752053
GO:0032991 protein-containing complex IEA --
genes like me logo Genes that share ontologies with NR0B2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NR0B2 Gene

Pathways & Interactions for NR0B2 Gene

genes like me logo Genes that share pathways with NR0B2: view

Pathways by source for NR0B2 Gene

1 KEGG pathway for NR0B2 Gene
1 GeneGo (Thomson Reuters) pathway for NR0B2 Gene
  • Transcription PPAR Pathway

SIGNOR curated interactions for NR0B2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NR0B2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,IBA 21873635
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0007219 Notch signaling pathway IEA --
GO:0007623 circadian rhythm IBA,IDA 28797635
GO:0008203 cholesterol metabolic process TAS 11030331
genes like me logo Genes that share ontologies with NR0B2: view

Drugs & Compounds for NR0B2 Gene

(8) Drugs for NR0B2 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
D-serine Approved, Experimental Pharma Target 0

(6) Additional Compounds for NR0B2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NR0B2: view

Transcripts for NR0B2 Gene

mRNA/cDNA for NR0B2 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR0B2

Alternative Splicing Database (ASD) splice patterns (SP) for NR0B2 Gene

No ASD Table

Relevant External Links for NR0B2 Gene

GeneLoc Exon Structure for
NR0B2

Expression for NR0B2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NR0B2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Heart (Cardiovascular System)

mRNA differential expression in normal tissues according to GTEx for NR0B2 Gene

This gene is overexpressed in Liver (x26.1), Pancreas (x6.0), Stomach (x5.1), and Adrenal Gland (x4.3).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NR0B2

SOURCE GeneReport for Unigene cluster for NR0B2 Gene:

Hs.427055

mRNA Expression by UniProt/SwissProt for NR0B2 Gene:

Q15466-NR0B2_HUMAN
Tissue specificity: Liver. Low levels of expression were detected in heart and pancreas.

Evidence on tissue expression from TISSUES for NR0B2 Gene

  • Pancreas(4.5)
  • Kidney(4.5)
  • Spleen(4.5)
  • Liver(3.5)
  • Intestine(3.2)
  • Gall bladder(2.7)
  • Muscle(2.4)
  • Heart(2.3)
  • Blood(2.3)
  • Stomach(2.1)
  • Adrenal gland(2.1)
genes like me logo Genes that share expression patterns with NR0B2: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NR0B2 Gene

Orthologs for NR0B2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NR0B2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NR0B2 29 30
  • 99.09 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NR0B2 29 30
  • 85.55 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NR0B2 29 30
  • 84.64 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nr0b2 29 16 30
  • 80.93 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nr0b2 29
  • 80.8 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia NR0B2 30
  • 54 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NR0B2 30
  • 51 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NR0B2 29 30
  • 65.7 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NR0B2 30
  • 35 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nr0b2 29
  • 49.53 (n)
Zebrafish
(Danio rerio)
Actinopterygii nr0b2a 29 30
  • 57.28 (n)
OneToMany
nr0b2b 30
  • 38 (a)
OneToMany
Dr.11590 29
Species where no ortholog for NR0B2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for NR0B2 Gene

ENSEMBL:
Gene Tree for NR0B2 (if available)
TreeFam:
Gene Tree for NR0B2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NR0B2: view image
Alliance of Genome Resources:
Additional Orthologs for NR0B2

Paralogs for NR0B2 Gene

Paralogs for NR0B2 Gene

(1) SIMAP similar genes for NR0B2 Gene using alignment to 1 proteins:

  • NR0B2_HUMAN
genes like me logo Genes that share paralogs with NR0B2: view

Variants for NR0B2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NR0B2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
1033992 Pathogenic: Obesity 26,913,409(-) CG/C
NM_021969.3(NR0B2):c.531del (p.Asp178fs)
FRAMESHIFT
rs113654931 Uncertain Significance: not provided 26,913,781(-) G/A
NM_021969.3(NR0B2):c.160C>T (p.Arg54Cys)
MISSENSE
rs139159423 Likely Benign: not provided 26,913,491(-) T/C
NM_021969.3(NR0B2):c.450A>G (p.Gln150=)
SYNONYMOUS
rs147871331 Benign: not provided 26,913,928(-) G/C
NM_021969.3(NR0B2):c.13C>G (p.Gln5Glu)
MISSENSE
rs151014108 Benign: not provided 26,913,468(-) C/T
NM_021969.3(NR0B2):c.473G>A (p.Ser158Asn)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NR0B2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NR0B2 Gene

Variant ID Type Subtype PubMed ID
nsv1000012 CNV gain 25217958
nsv508689 CNV deletion 20534489
nsv834524 CNV gain+loss 17160897

Variation tolerance for NR0B2 Gene

Residual Variation Intolerance Score: 84.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.19; 61.89% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NR0B2 Gene

Human Gene Mutation Database (HGMD)
NR0B2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NR0B2
Leiden Open Variation Database (LOVD)
NR0B2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NR0B2 Gene

Disorders for NR0B2 Gene

MalaCards: The human disease database

(25) MalaCards diseases for NR0B2 Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
body mass index quantitative trait locus 11
  • bmiq11
obesity due to melanocortin 4 receptor deficiency
  • mc4r deficiency
hemopneumothorax
  • haemopneumothorax
fibrolamellar carcinoma
  • fibrolamellar hepatocellular carcinoma
cholestasis
  • bile occlusion
- elite association - COSMIC cancer census association via MalaCards
Search NR0B2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NR0B2_HUMAN
  • Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269 PubMed:11136233}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Additional Disease Information for NR0B2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NR0B2: view

No data available for Genatlas for NR0B2 Gene

Publications for NR0B2 Gene

  1. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. (PMID: 11136233) Nishigori H … Takeda J (Proceedings of the National Academy of Sciences of the United States of America 2001) 3 4 22 40 72
  2. Structure and expression of the orphan nuclear receptor SHP gene. (PMID: 9603951) Lee HK … Choi HS (The Journal of biological chemistry 1998) 2 3 4 22
  3. Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A (p.G93D) variant with reduced functional activity. (PMID: 15459958) Echwald SM … Pedersen O (Human mutation 2004) 3 22 40
  4. RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP. (PMID: 28128295) Tsai TY … Wu Lee YH (Scientific reports 2017) 3 4
  5. Circadian rhythmicity: A functional connection between differentiated embryonic chondrocyte-1 (DEC1) and small heterodimer partner (SHP). (PMID: 28797635) Marczak MM … Yan B (Archives of biochemistry and biophysics 2017) 3 4

Products for NR0B2 Gene

Sources for NR0B2 Gene