ADRB1

protein-coding

adrenoceptor beta 1, the group of Adrenoceptors

Gene summary

The adrenergic receptors (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. Beta-1 adrenoceptors are predominately located in the heart. Specific polymorphisms in this gene have been shown to affect the resting heart rate and can be involved in heart failure. [provided by RefSeq, Sep 2019]

Previous symbols:

ADRB1R

MANE transcript

NM_000684.3

Inheritance

ClinVar variants

P:1U:57B:20

Top phenotype

Beta-blocker response, association with

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr10:114,043,866-114,046,904

External References & Databases

Ensembl (ENSG00000043591)

Transcript & Mutation Effects

hg38 • Region Span ~3.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short sleep, familial natural, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0020786

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Beta-blocker response, association withAD

Manifestation: Neurologic

Intervention: Pharmacogenomic

Rationale: The presence of variants may influence medication choice (eg, in congestive heart failure)

Refs: 10212248; 12197595; 12374873; 16844790; 17496726; 31473062

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADRB1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 12

SHORT SLEEP, FAMILIAL NATURAL, 2Total: 1

ADRB1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000684.3. 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				11 clinvar	4 clinvar	15
missense	1 clinvar		57 clinvar	1 clinvar	4 clinvar	63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	57	12	8	78

Highest pathogenic variant AF is 0.00012217554

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000684.3	RefSeq	NP_000675.1	1	MANE Select
ENST00000369295.4	Ensembl	ENSP00000358301.2	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
adrb1	Danio rerio	Structure: trunk Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

adrb1

Danio rerio

Structure: trunk

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of lipolysis in adipocytes - Homo sapiens (human)
Dilated cardiomyopathy (DCM) - Homo sapiens (human)
Gap junction - Homo sapiens (human)
Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)

Biological Process

positive regulation of heart rate by epinephrine-norepinephrine
positive regulation of the force of heart contraction by epinephrine-norepinephrine
diet induced thermogenesis
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure
G protein-coupled receptor signaling pathway

Molecular Function

adrenergic receptor activity
beta-adrenergic receptor activity
beta1-adrenergic receptor activity
Ras guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

early endosome
plasma membrane
integral component of plasma membrane
Schaffer collateral - CA1 synapse
integral component of postsynaptic density membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369295
Coding exons: 1
Length: 2862
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	1.70	148	219	0.677	0.0000105	2940
Missense (PolyPhen)		63	112.92	0.55793		1392
Synonymous	-1.18	119	104	1.15	0.00000516	1103
Loss of Function	0.312	9	10.1	0.894	4.38e-7	105

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: dbNSFP

Function: FUNCTION: Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. {ECO:0000269|PubMed:12391161}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium