ADRA2A

adrenoceptor alpha 2A, the group of Adrenoceptors

Basic information

Region (hg38): 10:111077029-111080907

Previous symbols: [ "ADRA2", "ADRA2R" ]

Links

ENSG00000150594 ∙ NCBI:150 ∙ OMIM:104210 ∙ HGNC:281 ∙ Uniprot:P08913 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lipodystrophy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipodystrophy, familial partial, type 8	AD	Cardiovascular; Endocrine	Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality	Cardiovascular; Endocrine; Musculoskeletal	27376152

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADRA2A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADRA2A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			25	2		27
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	3	3

Variants in ADRA2A

This is a list of pathogenic ClinVar variants found in the ADRA2A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-111078001-T-A		not specified	Uncertain significance (Nov 07, 2022)
10-111078033-T-C		not specified	Uncertain significance (Aug 22, 2023)
10-111078099-G-A		not specified	Uncertain significance (May 03, 2023)
10-111078100-G-A		not specified	Uncertain significance (Dec 19, 2022)
10-111078221-G-C		not specified	Benign (Dec 31, 2019)
10-111078249-C-T		not specified	Uncertain significance (Jun 29, 2023)
10-111078294-C-T		ADRA2A-related disorder	Uncertain significance (Dec 19, 2023)
10-111078348-A-G		not specified	Uncertain significance (Mar 30, 2024)
10-111078363-A-C		not specified	Uncertain significance (May 16, 2023)
10-111078377-C-G			Benign (Sep 19, 2018)
10-111078403-T-C		not specified	Uncertain significance (Apr 20, 2023)
10-111078459-G-A		not specified	Likely benign (Jan 19, 2018)
10-111078526-C-T		not specified	Uncertain significance (Jul 09, 2021)
10-111078579-G-A		not specified	Uncertain significance (Aug 30, 2021)
10-111078638-G-T		ADRA2A-related disorder	Likely benign (May 02, 2024)
10-111078678-A-G		not specified	Uncertain significance (Nov 08, 2021)
10-111078696-A-G		not specified	Uncertain significance (Mar 11, 2022)
10-111078732-C-G		not specified	Uncertain significance (Dec 27, 2023)
10-111078792-A-G		ADRA2A-related disorder	Uncertain significance (Jul 18, 2023)
10-111078799-TGGGCCCCGAGCGCAGCGC-T		not specified • ADRA2A-related disorder	Likely benign (Feb 12, 2021)
10-111078802-G-A		not specified	Uncertain significance (Jan 02, 2024)
10-111078811-G-T		not specified	Uncertain significance (Mar 25, 2024)
10-111078836-G-A		ADRA2A-related disorder	Likely benign (Jul 28, 2024)
10-111078862-A-G		not specified	Uncertain significance (Dec 16, 2023)
10-111078867-G-A		not specified	Uncertain significance (Apr 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADRA2A	protein_coding	protein_coding	ENST00000280155	1	3869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000818	0.796	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.80	172	252	0.681	0.0000172	2917
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;Monoamine GPCRs;Signaling by GPCR;Signal Transduction;Metabolism;Adrenaline,noradrenaline inhibits insulin secretion;Adrenoceptors;Amine ligand-binding receptors;Regulation of insulin secretion;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Adrenaline signalling through Alpha-2 adrenergic receptor;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;Hemostasis;G alpha (i) signalling events;G alpha (z) signalling events;Integration of energy metabolism;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.114

Haploinsufficiency Scores

• pHI: 0.190
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.635

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adra2a
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• 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;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;Ras protein signal transduction;Rho protein signal transduction;positive regulation of cell population proliferation;negative regulation of norepinephrine secretion;regulation of vasoconstriction;actin cytoskeleton organization;platelet activation;positive regulation of cell migration;activation of protein kinase activity;activation of protein kinase B activity;negative regulation of epinephrine secretion;cellular response to hormone stimulus;receptor transactivation;glucose homeostasis;positive regulation of potassium ion transport;positive regulation of MAP kinase activity;positive regulation of MAPK cascade;positive regulation of epidermal growth factor-activated receptor activity;negative regulation of calcium ion-dependent exocytosis;negative regulation of insulin secretion;regulation of insulin secretion;intestinal absorption;negative regulation of lipid catabolic process;positive regulation of membrane protein ectodomain proteolysis;negative regulation of calcium ion transport;negative regulation of insulin secretion involved in cellular response to glucose stimulus;adrenergic receptor signaling pathway;adenylate cyclase-activating adrenergic receptor signaling pathway;adenylate cyclase-inhibiting adrenergic receptor signaling pathway;phospholipase C-activating adrenergic receptor signaling pathway;positive regulation of wound healing;negative regulation of calcium ion transmembrane transporter activity
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;basolateral plasma membrane;receptor complex
• Molecular function: adrenergic receptor activity;alpha2-adrenergic receptor activity;protein binding;protein kinase binding;alpha-1B adrenergic receptor binding;alpha-2C adrenergic receptor binding;thioesterase binding;heterotrimeric G-protein binding;protein homodimerization activity;protein heterodimerization activity;epinephrine binding;norepinephrine binding