ADRA2C

adrenoceptor alpha 2C, the group of Adrenoceptors

Basic information

Region (hg38): 4:3766348-3768526

Previous symbols: [ "ADRA2L2", "ADRA2RL2" ]

Links

ENSG00000184160 ∙ NCBI:152 ∙ OMIM:104250 ∙ HGNC:283 ∙ Uniprot:P18825 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Beta-blocker response, association with	AD	Pharmacogenomic	The presence of variants may influence medication choice (eg, in congestive heart failure)	General	17496726

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADRA2C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADRA2C 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				5	2	7
missense			27		1	28
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	27	6	3

Variants in ADRA2C

This is a list of pathogenic ClinVar variants found in the ADRA2C region.

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

Position	Type	Phenotype	Significance	ClinVar
4-3766617-C-A		not specified	Uncertain significance (Jan 10, 2023)
4-3766653-C-T		not specified	Uncertain significance (Mar 19, 2024)
4-3766706-G-A		not specified	Uncertain significance (Aug 28, 2023)
4-3766706-G-T		not specified	Uncertain significance (May 08, 2023)
4-3766710-C-T		not specified	Uncertain significance (Oct 06, 2021)
4-3766725-G-A		not specified	Uncertain significance (Dec 06, 2021)
4-3766728-C-T		not specified	Uncertain significance (Jun 10, 2024)
4-3766740-A-G		not specified	Uncertain significance (Feb 27, 2023)
4-3766806-T-C		not specified	Uncertain significance (Apr 19, 2024)
4-3766903-G-C		ADRA2C-related disorder	Likely benign (Nov 17, 2021)
4-3766918-C-A		ADRA2C-related disorder	Likely benign (Sep 30, 2019)
4-3767085-A-C		not specified	Uncertain significance (Oct 25, 2023)
4-3767199-C-A		not specified	Uncertain significance (Jul 12, 2023)
4-3767313-T-C		not specified	Uncertain significance (Nov 07, 2022)
4-3767337-T-G		not specified	Uncertain significance (Jan 10, 2023)
4-3767367-A-T		not specified	Uncertain significance (Dec 16, 2022)
4-3767384-A-G		not specified	Uncertain significance (Jun 07, 2023)
4-3767393-G-A		not specified	Uncertain significance (Jul 09, 2021)
4-3767409-C-T		not specified	Uncertain significance (Dec 27, 2023)
4-3767426-G-C		not specified	Uncertain significance (Jul 08, 2022)
4-3767444-C-T		not specified	Uncertain significance (Apr 07, 2022)
4-3767460-C-T		not specified	Uncertain significance (Apr 09, 2024)
4-3767464-C-G		not specified	Uncertain significance (Apr 13, 2022)
4-3767480-G-C		not specified	Uncertain significance (Mar 04, 2024)
4-3767483-G-C		not specified	Uncertain significance (Aug 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADRA2C	protein_coding	protein_coding	ENST00000330055	1	2177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.502	0.495	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	161	231	0.696	0.0000118	2868
Missense in Polyphen		57	116.45	0.48946		1252
Synonymous	-0.652	118	109	1.08	0.00000579	1066
Loss of Function	2.41	2	10.4	0.192	4.51e-7	107

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.
• 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;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: 0.0996

Haploinsufficiency Scores

• pHI: 0.0333
• hipred: Y
• hipred_score: 0.735
• ghis: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.825

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adra2c
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); 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)

Gene ontology

• Biological process: 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 vasoconstriction;regulation of insulin secretion;regulation of sensory perception of pain;negative regulation of uterine smooth muscle contraction;adrenergic receptor signaling pathway;adenylate cyclase-activating adrenergic receptor signaling pathway
• Cellular component: cytoplasm;endosome;plasma membrane;integral component of plasma membrane;axon terminus;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: adrenergic receptor activity;alpha2-adrenergic receptor activity;protein binding;alpha-2A adrenergic receptor binding;protein homodimerization activity;protein heterodimerization activity;epinephrine binding