ADORA2B

Chr 17

adenosine A2b receptor

Also known as: ADORA2

NCBI Gene: 136ENSG00000170425UniProt: P29275

This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

97
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ADORA2B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 65 VUS of 97 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.49LOEUF
pLI 0.000
Z-score 0.49
OE 0.83 (0.49–1.49)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.06Z-score
OE missense 1.01 (0.90–1.14)
182 obs / 179.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.83 (0.49–1.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.90–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 8 / 9.6Missense obs/exp: 182 / 179.9Syn Z: 0.43

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
VUS65
Likely Benign2
Benign4
26
Pathogenic
65
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
0
0
0
VUS
0
46
19
0
65
Likely Benign
0
0
2
0
2
Benign
0
1
0
3
4
Total04747397

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

View in ClinVar →

Protein Context — Lollipop Plot

ADORA2B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADORA2B promotes proliferation and migration in head and neck squamous cell carcinoma and is associated with immune infiltration.
Li P et al.·BMC Cancer
2025
A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction.
Gile J et al.·Curr Pharm Des
2020
HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis.
Philip K et al.·FASEB J
2017
Adenosine and hyaluronan promote lung fibrosis and pulmonary hypertension in combined pulmonary fibrosis and emphysema.
Collum SD et al.·Dis Model Mech
2019
Integrating machine learning and molecular dynamics simulation to decipher the molecular network of dioxin-associated liposarcoma.
Chenhe Z et al.·Sci Rep
2025
Comprehensive analysis of pyroptosis-related gene signatures in renal fibrosis.
Zhang DH et al.·Clin Exp Nephrol
2025
Adenosine A2b receptor promotes progression of human oral cancer.
Kasama H et al.·BMC Cancer
2015
Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer.
Shreenivas A et al.·Int J Mol Sci
2024
CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation.
Murphy SA et al.·J Immunother Cancer
2026
The association of ADORA2A and ADORA2B polymorphisms with the risk and severity of chronic heart failure: a case-control study of a northern Chinese population.
Zhai YJ et al.·Int J Mol Sci
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Diastolic Heart FailureHeart Failure With Preserved Ejection Fraction

Purinergic Signaling and the Postmenopausal Heart

RECRUITING
NCT06015776Beth Israel Deaconess Medical CenterStarted 2019-07-01
Gender

External Resources

Links to major genomics databases and tools