ADRA2A

Chr 10AD

adrenoceptor alpha 2A

Also known as: ADRA2, ADRA2R, ADRAR, ALPHA2AAR, FPLD8

NCBI Gene: 150ENSG00000150594UniProt: P08913OMIM: 104210

The ADRA2A protein is a G protein-coupled receptor for catecholamines that inhibits adenylyl cyclase and regulates neurotransmitter release from sympathetic and central nervous system terminals, controlling blood pressure, lipolysis, and insulin release. Mutations cause familial partial lipodystrophy type 8 with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variation (pLI 0.0008, LOEUF 1.23), suggesting that complete loss of function may be tolerated.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.231 OMIM phenotype
Clinical Summary— ADRA2A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 68 VUS of 104 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ADRA2A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.001
Z-score 1.08
OE 0.62 (0.34–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.80Z-score
OE missense 0.68 (0.60–0.77)
172 obs / 252.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.34–1.23)
0≤0.351.4
Missense OE0.68 (0.60–0.77)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 6 / 9.6Missense obs/exp: 172 / 252.5Syn Z: 1.27
DN
0.7326th %ile
GOF
0.80top 10%
LOF
0.3452th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS68
Likely Benign8
Benign3
23
Pathogenic
2
Likely Pathogenic
68
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
0
64
4
0
68
Likely Benign
0
3
3
2
8
Benign
0
0
0
3
3
Total067325104

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

View in ClinVar →

Protein Context — Lollipop Plot

ADRA2A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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