ADRA1A

adrenoceptor alpha 1A, the group of Adrenoceptors

Basic information

Region (hg38): 8:26748149-26867278

Previous symbols: [ "ADRA1C" ]

Links

ENSG00000120907 ∙ NCBI:148 ∙ OMIM:104221 ∙ HGNC:277 ∙ Uniprot:P35348 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADRA1A gene.

• Inborn genetic diseases (18 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADRA1A 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					4	4
missense			18		1	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	0	5

Variants in ADRA1A

This is a list of pathogenic ClinVar variants found in the ADRA1A region.

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

Position	Type	Phenotype	Significance	ClinVar
8-26770163-C-T		not specified	Uncertain significance (Aug 29, 2022)
8-26770229-G-C		not specified	Uncertain significance (Oct 24, 2023)
8-26770282-C-T		not specified	Uncertain significance (Sep 23, 2023)
8-26770315-A-G		not specified	Uncertain significance (Mar 08, 2024)
8-26770347-A-C			Benign (Feb 25, 2018)
8-26770462-G-C		not specified	Uncertain significance (May 09, 2023)
8-26770510-C-T		not specified	Uncertain significance (Jun 06, 2023)
8-26770519-T-G		not specified	Uncertain significance (Oct 10, 2023)
8-26864093-G-A		not specified	Uncertain significance (Aug 04, 2021)
8-26864101-A-G		not specified	Uncertain significance (May 05, 2023)
8-26864151-C-A			Benign (Dec 28, 2017)
8-26864227-A-G		not specified	Uncertain significance (Oct 06, 2022)
8-26864233-C-T		not specified	Uncertain significance (Mar 02, 2023)
8-26864247-G-T			Benign (Apr 04, 2018)
8-26864297-C-G		not specified	Uncertain significance (Oct 25, 2022)
8-26864309-C-T		not specified	Uncertain significance (Dec 16, 2023)
8-26864324-G-C		not specified	Uncertain significance (Oct 06, 2023)
8-26864404-G-T		not specified	Uncertain significance (Jun 05, 2023)
8-26864495-T-C		not specified	Uncertain significance (Jan 17, 2023)
8-26864508-G-C			Benign (Jul 04, 2018)
8-26864509-G-A		not specified	Uncertain significance (Sep 26, 2022)
8-26864510-A-C			Benign (Jul 06, 2018)
8-26864518-C-G		not specified	Uncertain significance (Jan 17, 2024)
8-26864566-G-A		not specified	Uncertain significance (Mar 24, 2023)
8-26864594-T-G		not specified	Uncertain significance (Sep 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADRA1A	protein_coding	protein_coding	ENST00000380586	3	119124

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.37e-7	0.345	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0131	268	267	1.00	0.0000143	3048
Missense in Polyphen		119	122.03	0.97518		1377
Synonymous	-1.66	140	117	1.20	0.00000690	1016
Loss of Function	0.526	11	13.0	0.843	6.13e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000293	0.000293
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000735	0.000730
Middle Eastern	0.000218	0.000217
South Asian	0.000131	0.000131
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}.
• Pathway: AMPK signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Sympathetic Nerve Pathway (Neuroeffector Junction);Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;AMP-activated Protein Kinase (AMPK) Signaling;Endothelin Pathways;Serotonin and anxiety;GPCRs, Class A Rhodopsin-like;Calcium Regulation in the Cardiac Cell;Monoamine GPCRs;Signaling by GPCR;Signal Transduction;Adrenoceptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (12/13) signalling events;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.746
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

• pHI: 0.0435
• hipred: N
• hipred_score: 0.400
• ghis: 0.389

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adra1a
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary 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); 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)

Gene ontology

• Biological process: negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure;norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure;positive regulation of heart rate by epinephrine-norepinephrine;positive regulation of the force of heart contraction by epinephrine-norepinephrine;positive regulation of systemic arterial blood pressure;apoptotic process;smooth muscle contraction;signal transduction;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;activation of phospholipase C activity;positive regulation of cytosolic calcium ion concentration;cell-cell signaling;adult heart development;aging;negative regulation of cell population proliferation;response to hormone;negative regulation of autophagy;positive regulation of cardiac muscle hypertrophy;positive regulation of synaptic transmission, GABAergic;negative regulation of Rho protein signal transduction;intracellular signal transduction;response to drug;positive regulation of MAPK cascade;positive regulation of action potential;positive regulation of vasoconstriction;positive regulation of smooth muscle contraction;micturition;calcium ion transport into cytosol;positive regulation of cardiac muscle contraction;cell growth involved in cardiac muscle cell development;positive regulation of ERK1 and ERK2 cascade;adenylate cyclase-activating adrenergic receptor signaling pathway;positive regulation of protein kinase C signaling;pilomotor reflex;positive regulation of non-membrane spanning protein tyrosine kinase activity;regulation of synaptic vesicle exocytosis
• Cellular component: nucleus;cytoplasm;plasma membrane;integral component of plasma membrane;caveola;Z disc;T-tubule;nuclear membrane;dopaminergic synapse;glutamatergic synapse;GABA-ergic synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: adrenergic receptor activity;alpha1-adrenergic receptor activity;protein binding;protein heterodimerization activity