ADRA2A

protein-coding

adrenoceptor alpha 2A, the group of Adrenoceptors

Gene summary

Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]

Previous symbols:

ADRA2
ADRA2R

MANE transcript

NM_000681.4

Inheritance

ClinVar variants

P:1U:65B:11

Top phenotype

Lipodystrophy, familial partial, type 8

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr10:111,077,029-111,080,907

External References & Databases

Ensembl (ENSG00000150594)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lipodystrophyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0006573

Submitter: Ambry Genetics

lipodystrophy, familial partial, type 8LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0958022

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Lipodystrophy, familial partial, type 8AD

Manifestation: Cardiovascular; Endocrine; Musculoskeletal

Intervention: Cardiovascular; Endocrine

Rationale: Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality

Refs: 27376152

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADRA2A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

ADRA2A-related disorderTotal: 7

not providedTotal: 5

Lipodystrophy, familial partial, type 8Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000681.4. 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				5 clinvar	3 clinvar	8
missense	1 clinvar		65 clinvar	3 clinvar		69
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	65	8	3	77

Highest pathogenic variant AF is 6.846014e-7

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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_000681.4	RefSeq	NP_000672.3	1	MANE Select
ENST00000280155.4	Ensembl	ENSP00000280155.2	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
Antiarrhythmic Pathway, Pharmacodynamics
Sympathetic Nerve Pathway (Neuroeffector Junction)
GPCRs, Class A Rhodopsin-like

Biological Process

positive regulation of cytokine production
regulation of smooth muscle contraction
G protein-coupled receptor signaling pathway
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

adrenergic receptor activity
alpha2-adrenergic receptor activity
protein binding
protein kinase binding
alpha-1B adrenergic receptor binding

Cellular Component

cytoplasm
plasma membrane
integral component of plasma membrane
basolateral plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000280155
Coding exons: 1
Length: 3869
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	1.80	172	252	0.681	0.0000172	2917
Missense (PolyPhen)		94	159.39	0.58974		1576
Synonymous	1.27	107	125	0.856	0.00000907	1034
Loss of Function	1.08	6	9.61	0.624	4.15e-7	111

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: Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. {ECO:0000269|PubMed:23105096}.;

Recessive Scores

pRec: 0.114

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.635

Gene Damage Prediction

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