ADRA2B

Chr 2

adrenoceptor alpha 2B

Also known as: ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, FAME2, alpha-2BAR

NCBI Gene: 151ENSG00000274286UniProt: P18089

The alpha-2B adrenergic receptor is a G protein-coupled receptor that inhibits adenylyl cyclase and regulates neurotransmitter release from sympathetic and central adrenergic neurons, controlling blood pressure, lipolysis, and insulin release. Mutations cause autosomal dominant developmental and epileptic encephalopathy with movement abnormalities. This gene is not highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

UniProtEpilepsy, familial adult myoclonic, 2
0
Active trials
4
Pubs (1 yr)
32
P/LP submissions
3%
P/LP missense
1.22
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ADRA2B
🧬
Gene-Disease Validity (ClinGen)
epilepsy · ADRefuted

Refuted — evidence has disproved this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 86 VUS of 142 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.22LOEUF
pLI 0.000
Z-score 0.97
OE 0.72 (0.44–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.94 (0.85–1.04)
270 obs / 287.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.44–1.22)
0≤0.351.4
Missense OE0.94 (0.85–1.04)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 10 / 13.9Missense obs/exp: 270 / 287.4Syn Z: 1.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedADRA2B-related intellectual developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.82top 10%
LOF
0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic11
VUS86
Likely Benign18
Benign4
Conflicting1
21
Pathogenic
11
Likely Pathogenic
86
VUS
18
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
1
10
0
11
VUS
2
46
38
0
86
Likely Benign
0
4
6
8
18
Benign
0
0
1
3
4
Conflicting
—1
Total2517611141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADRA2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients