ADRA1A
protein-codingadrenoceptor alpha 1A, the group of Adrenoceptors
Gene summary
Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties. [provided by RefSeq, Jul 2008]
- ADRA1C
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~119.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADRA1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000680.4. 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 | 4 | 4 | ||||
| missense | 66 | 1 | 1 | 68 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 67 | 1 | 5 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000671.2 | 2 | MANE Select | |
| Ensembl | ENSP00000369947.3 | 2 | MANE Select | |
| RefSeq | NP_001309431.1 | 2 | Standard | |
| RefSeq | NP_001309432.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
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
Molecular Function
- adrenergic receptor activity
- alpha1-adrenergic receptor activity
- protein binding
- protein heterodimerization activity
Cellular Component
- nucleus
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- caveola
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380586
- Coding exons
- 3
- Length
- 119124
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 103
- Defined
- 125748
- p
- 0.000410
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0131 | 268 | 267 | 1.00 | 0.0000143 | 3048 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00073 | 0.00073 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.746
- RVIS EVS
- 0.16
- RVIS percentile EVS
- 64.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0809
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |