ADRB2
protein-codingadrenoceptor beta 2, the group of Adrenoceptors
Gene summary
This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]
- ADRB2R
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010940
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Selection of medications (eg, in asthma treatment) may be influenced by the presence of certain variants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADRB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000024.6. 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 | 12 | 2 | 14 | |||
| missense | 11 | 1 | 3 | 15 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 11 | 13 | 5 | 29 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000015.2 | 1 | MANE Select | |
| Ensembl | ENSP00000305372.4 | 1 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adrb2a | Danio rerio | Structure: integument Quality: decreased pigmentation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of lipolysis in adipocytes - Homo sapiens (human)
- Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Renin secretion - Homo sapiens (human)
Biological Process
- diet induced thermogenesis
- norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure
- regulation of sodium ion transport
- desensitization of G protein-coupled receptor signaling pathway by arrestin
- receptor-mediated endocytosis
Molecular Function
- amyloid-beta binding
- adrenergic receptor activity
- beta2-adrenergic receptor activity
- protein binding
- adenylate cyclase binding
Cellular Component
- nucleus
- lysosome
- endosome
- early endosome
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305988
- Coding exons
- 1
- Length
- 2041
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 180 | 239 | 0.755 | 0.0000141 | 2728 |
| Missense (PolyPhen) | 32 | 76.146 | 0.42025 | 924 | ||
| Synonymous | -0.225 | 101 | 98.2 | 1.03 | 0.00000608 | 826 |
| Loss of Function | 2.46 | 2 | 10.7 | 0.188 | 4.69e-7 | 124 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| 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. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. {ECO:0000269|PubMed:2831218, ECO:0000269|PubMed:7915137}.;
Recessive Scores
- pRec
- 0.802
Intolerance Scores
- LoFtool
- 0.396
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.430
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |