NR0B2
protein-codingnuclear receptor subfamily 0 group B member 2, the group of Nuclear receptor subfamily 0 group B
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019182
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NR0B2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021969.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 27 | 28 | |||
| missense | 111 | 3 | 2 | 116 | ||
| nonsense | 1 | 1 | 3 | 5 | ||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 4 | 1 | 8 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 4 | 120 | 31 | 2 | 158 |
Highest pathogenic variant AF is 0.00006400258
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068804.1 | 2 | MANE Select | |
| Ensembl | ENSP00000254227.3 | 2 | MANE Select | |
| Ensembl | ENSP00000772530.1 | 2 | Standard | |
| Ensembl | ENSP00000772531.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Bile secretion - Homo sapiens (human)
- NHR
- Androgen receptor signaling pathway
- Farnesoid X Receptor Pathway
- Estrogen Receptor Pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- transcription initiation from RNA polymerase II promoter
- Notch signaling pathway
- cholesterol metabolic process
- response to glucose
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- steroid hormone receptor activity
- transcription corepressor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000254227
- Coding exons
- 2
- Length
- 2478
- Individuals with no LoFs
- 125558
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 190
- Defined
- 125748
- p
- 0.000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.250 | 146 | 155 | 0.944 | 0.00000928 | 1636 |
| Missense (PolyPhen) | 43 | 45.046 | 0.95459 | 574 | ||
| Synonymous | 1.03 | 54 | 64.5 | 0.838 | 0.00000354 | 573 |
| Loss of Function | 0.180 | 8 | 8.57 | 0.934 | 4.50e-7 | 80 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0075 | 0.0073 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.00073 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. 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. {ECO:0000269|PubMed:14752053}.;
- Disease
- DISEASE: 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 variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.661
Intolerance Scores
- LoFtool
- 0.359
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |