ADRA2B

adrenoceptor alpha 2B, the group of Adrenoceptors

Basic information

Region (hg38): 2:96112876-96116571

Previous symbols: [ "ADRA2L1", "ADRA2RL1" ]

Links

ENSG00000274286 ∙ NCBI:151 ∙ OMIM:104260 ∙ HGNC:282 ∙ Uniprot:P18089 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• benign adult familial myoclonic epilepsy (Supportive), mode of inheritance: AD
• epilepsy, familial adult myoclonic, 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, myoclonic, familial adult, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	24114805
As with many disorders involving seizures, appropriate interventions may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADRA2B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADRA2B 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				8	3	11
missense			23	3		26
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			1	1	2	4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	27	13	5

Variants in ADRA2B

This is a list of pathogenic ClinVar variants found in the ADRA2B region.

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

Position	Type	Phenotype	Significance	ClinVar
2-96114795-G-T		ADRA2B-related disorder	Likely benign (Sep 23, 2019)
2-96114857-C-T			Likely benign (Feb 26, 2018)
2-96114884-G-A			Likely benign (Jan 03, 2019)
2-96114908-G-A			Likely benign (Jan 01, 2024)
2-96114917-G-A		ADRA2B-related disorder	Likely benign (Jun 16, 2022)
2-96114964-T-C			Uncertain significance (Dec 27, 2020)
2-96115015-C-T			Likely benign (Dec 31, 2019)
2-96115023-A-C		not specified	Uncertain significance (Dec 13, 2021)
2-96115024-C-T		ADRA2B-related disorder	Likely benign (Mar 07, 2019)
2-96115048-G-A			Uncertain significance (Jan 01, 2020)
2-96115057-G-A			Uncertain significance (Dec 19, 2023)
2-96115071-C-T			Uncertain significance (Oct 02, 2020)
2-96115080-C-T		ADRA2B-related disorder	not provided (-)
2-96115092-C-T			Uncertain significance (Nov 10, 2023)
2-96115207-C-G			Uncertain significance (Mar 15, 2021)
2-96115207-C-T			Likely benign (Apr 16, 2018)
2-96115238-CTCCTCCTCT-C			Benign (Dec 19, 2019)
2-96115238-C-CTCCTCT			Likely benign (Jul 06, 2018)
2-96115238-C-CTCCTCCTCT		ADRA2B-related disorder	Benign (Mar 17, 2020)
2-96115251-T-TCCTCTTCCC		Seizure	Uncertain significance (Sep 13, 2019)
2-96115276-A-G		not specified	Uncertain significance (Dec 03, 2021)
2-96115314-T-C			Uncertain significance (Nov 10, 2023)
2-96115367-G-A		ADRA2B-related disorder	Likely benign (Dec 08, 2021)
2-96115455-G-C			Uncertain significance (Aug 30, 2021)
2-96115464-AAAGCCCCACCA-CTGCCAAAC		Epilepsy, familial adult myoclonic, 2	Uncertain significance (Jan 01, 2014)

GnomAD

Source: gnomAD

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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol. {ECO:0000269|PubMed:23105096}.
• Disease: DISEASE: Epilepsy, familial adult myoclonic, 2 (FAME2) [MIM:607876]: A form of cortical myoclonic tremor with epilepsy, a syndrome characterized by cortical myoclonus and variable occurrence of epileptic seizures. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom; both complex partial as well as generalized tonic clonic seizures are described. Some patients exhibit mild cognitive impairment. {ECO:0000269|PubMed:24114805}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Sympathetic Nerve Pathway (Neuroeffector Junction);GPCRs, Class A Rhodopsin-like;Monoamine GPCRs;Signaling by GPCR;Signal Transduction;Adrenoceptors;Amine ligand-binding receptors;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;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.761
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.238

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.450

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adra2b
• Phenotype: respiratory system phenotype; embryo 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); reproductive system phenotype; 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); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; muscle phenotype

Gene ontology

• Biological process: activation of MAPK activity;regulation of vascular smooth muscle contraction;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;cell-cell signaling;female pregnancy;negative regulation of norepinephrine secretion;platelet activation;activation of protein kinase B activity;negative regulation of epinephrine secretion;receptor transactivation;positive regulation of MAPK cascade;positive regulation of neuron differentiation;positive regulation of blood pressure;positive regulation of uterine smooth muscle contraction;adrenergic receptor signaling pathway;adenylate cyclase-activating adrenergic receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface
• Molecular function: adrenergic receptor activity;alpha2-adrenergic receptor activity;protein binding;epinephrine binding