ADRB3
protein-codingadrenoceptor beta 3, the group of Adrenoceptors
Gene summary
The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor is located mainly in the adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Obesity and bodyweight-related disorders are correlated with certain polymorphisms in three subtypes of beta-adrenoceptor, among them, the ADRB3 gene.[provided by RefSeq, Oct 2019]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADRB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000025.3. 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 | 1 | 2 | |||
| missense | 59 | 3 | 1 | 63 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 60 | 4 | 2 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000016.1 | 2 | MANE Select | |
| Ensembl | ENSP00000343782.3 | 2 | MANE Select | |
| Ensembl | ENSP00000808083.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adrb3b | Danio rerio | Structure: vertebra 2 Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of lipolysis in adipocytes - Homo sapiens (human)
- Thermogenesis - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Renin secretion - Homo sapiens (human)
- Salivary secretion - Homo sapiens (human)
Biological Process
- norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure
- desensitization of G protein-coupled receptor signaling pathway by arrestin
- carbohydrate metabolic process
- generation of precursor metabolites and energy
- energy reserve metabolic process
Molecular Function
- adrenergic receptor activity
- beta-adrenergic receptor activity
- protein binding
- beta3-adrenergic receptor activity
- protein homodimerization activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000345060
- Coding exons
- 2
- Length
- 3968
- Individuals with no LoFs
- 125126
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125150
- p
- 0.0000959
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.406 | 214 | 231 | 0.925 | 0.0000107 | 2476 |
| Missense (PolyPhen) | 97 | 113.51 | 0.85454 | 1253 | ||
| Synonymous | 0.104 | 109 | 110 | 0.987 | 0.00000532 | 966 |
| Loss of Function | -0.0646 | 10 | 9.78 | 1.02 | 4.23e-7 | 89 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.000062 | rare |
| Latino/Admixed American | 0.00024 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00068 | 0.00065 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000093 | 0.0000089 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.;
Recessive Scores
- pRec
- 0.420
Intolerance Scores
- LoFtool
- 0.150
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.448
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |