Affinage

ADORA2A

Adenosine receptor A2a · UniProt P29274

Length
412 aa
Mass
44.7 kDa
Annotated
2026-06-09
73 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADORA2A encodes a G protein-coupled adenosine A2A receptor that, upon adenosine binding, activates adenylyl cyclase and the cAMP cascade — an activity reconstituted in multiple heterologous expression systems and blocked by adenosine deaminase and A2 receptor antagonists (PMID:2125216). In the brain it is expressed selectively by enkephalin-containing, D2-type medium spiny neurons of the striatum, and its regulatory elements are sufficient to drive D2-MSN-specific expression in mice and non-human primates (PMID:1713612, PMID:39548191). Through cAMP/PKA the receptor signals in diverse peripheral tissues: it drives osteogenic differentiation (PMID:32432317), promotes white adipose lipolysis by reducing methylation of the HSL promoter (PMID:39976204), and supports endothelial functions including Stat3/Akt-dependent angiogenesis (PMID:37051927) and, when active in vascular endothelium, blood-brain barrier breakdown and associated cognitive impairment (PMID:30886019). In cancer contexts ADORA2A promotes survival and progression: it sustains colorectal carcinoma proliferation and invasion via PI3K/AKT (PMID:37945707), and rewires proline metabolism through an ERK/MYC/PYCR cascade that fuels SIRT6/7-mediated H3K27 deacetylation to drive a neuroendocrine transcriptional program in prostate and lung cancer (PMID:38099497). The receptor also forms heterodimers with the dopamine D2 receptor (DRD2), acting upstream of DRD2/ERK signaling in retinal cells to modulate processes including myopia progression (PMID:35724635, PMID:41533917). ADORA2A expression is itself epigenetically controlled — induced by JMJD3-mediated H3K27me3 demethylation in macrophages (PMID:36456564) and repressed by miR-195/miR-497 and promoter methylation (PMID:32432317) — and common diplotype variation functionally tunes its mRNA, protein, and cAMP output (PMID:23535492).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1990 High

    Established that the orphan clone RDC8 encodes a functional adenosine A2 receptor coupled to cAMP, defining the receptor's core biochemical activity.

    Evidence Heterologous expression in Y1 adrenal cells, thyrocytes, Xenopus oocytes and COS7 cells with adenylyl cyclase and radioligand binding assays plus pharmacological inhibition

    PMID:2125216

    Open questions at the time
    • No structural basis for adenosine binding or G protein coupling defined
    • Did not address endogenous tissue distribution or physiological role
  2. 1991 Medium

    Localized receptor expression to a defined neuronal population, linking ADORA2A to striatal circuitry by showing it marks enkephalinergic medium spiny neurons.

    Evidence In situ hybridization with neurochemical phenotyping in rat caudate-putamen

    PMID:1713612

    Open questions at the time
    • Descriptive expression mapping without functional consequence
    • Rodent striatum only
  3. 1996 Medium

    Resolved the human gene architecture and chromosomal position, providing the genomic substrate for later variant and regulatory studies.

    Evidence Genomic cloning, FISH, and PCR of human-hamster hybrid panels

    PMID:8670304

    Open questions at the time
    • No regulatory element or promoter function assigned
    • No link to phenotype
  4. 2013 Medium

    Demonstrated that common ADORA2A haplotype variation functionally alters signaling output, connecting genotype to expression and cAMP response.

    Evidence Diplotype-stratified mRNA, Western blot, and cAMP assays in human brain and lymphoblasts

    PMID:23535492

    Open questions at the time
    • Correlative across genotype groups, no causal allelic substitution
    • Single lab
  5. 2019 High

    Showed that endothelial ADORA2A signaling causally drives blood-brain barrier breakdown and cognitive impairment, defining a vascular role distinct from its neuronal one.

    Evidence Endothelial-specific inducible Adora2a knockout with BBB permeability, EM, behavior and LTP readouts plus pharmacology

    PMID:30886019

    Open questions at the time
    • Downstream effector pathway in endothelium not resolved
    • Mouse model only
  6. 2020 Medium

    Connected ADORA2A to angiogenesis and immune tone, identifying Stat3/Akt-dependent angiogenesis and a genotype-linked pro-inflammatory phenotype with reduced receptor expression.

    Evidence Placental endothelial angiogenesis and Matrigel assays with pStat3/pAkt readouts (37051927); rs2298383-stratified PBMC RT-qPCR of ADORA2A/IFNG (32182774)

    PMID:32182774 PMID:37051927

    Open questions at the time
    • Immune correlation is associative, no mechanistic link to IFNG transcription
    • Two distinct tissue contexts not integrated
  7. 2020 Medium

    Established ADORA2A as a node controlled by miRNA and promoter methylation that drives osteogenic differentiation through cAMP/PKA.

    Evidence Luciferase 3'UTR target validation, bisulfite sequencing, demethylation, and cAMP/PKA analysis in OPLL PLL cells

    PMID:32432317

    Open questions at the time
    • Disease specificity to OPLL not generalized
    • Single lab
  8. 2022 Medium

    Defined epigenetic and dimerization-based control of the receptor: JMJD3/H3K27me3 induces ADORA2A to suppress macrophage apoptosis, and ADORA2A heterodimerizes with DRD2 to inhibit DRD2/ERK signaling.

    Evidence ChIP at ADORA2A locus with apoptosis assays in ALI model (36456564); co-IP, co-localization and ERK readouts in RPE cells (35724635)

    PMID:35724635 PMID:36456564

    Open questions at the time
    • Anti-apoptotic mechanism downstream of receptor not detailed
    • Heterodimer interface and stoichiometry undefined
  9. 2023 High

    Revealed two pro-survival/pro-progression cancer axes: an ERK/MYC/PYCR-proline-SIRT6/7-H3K27 deacetylation cascade driving neuroendocrine plasticity, and PI3K/AKT-driven proliferation in colorectal carcinoma.

    Evidence GEMM Adora2a ablation with metabolomics, ChIP, RNA-seq and pharmacology (38099497); reciprocal knockdown/overexpression with PI3K/AKT and apoptosis readouts in colorectal lines (37945707)

    PMID:37945707 PMID:38099497

    Open questions at the time
    • How adenosine signaling selectively engages ERK/MYC vs PI3K/AKT in different tumors unclear
    • Renoprotective genistein-ADORA2A axis (36932924) characterized only correlatively
  10. 2024 High

    Used genetic epistasis to place retinal ADORA2A upstream of DRD2 in controlling myopia, and positioned ADORA2A downstream of RagA-p70S6K signaling in depression-related behavior.

    Evidence Retina-specific and Drd2 double-KO epistasis with KW6002 pharmacology (41533917); RagA transgenic mice with RNA-seq and istradefylline rescue (39373701); MiniPromoter D2-MSN expression mapping (39548191)

    PMID:39373701 PMID:39548191 PMID:41533917

    Open questions at the time
    • Molecular basis of ADORA2A-DRD2 functional epistasis in retina not resolved
    • Connection between RagA pathway and ADORA2A transcription not mechanistically defined
  11. 2025 Medium

    Extended ADORA2A signaling to metabolic and vascular pathology, linking CD73-derived adenosine to HSL-driven lipolysis and PARP1/POLG-driven mitochondrial dysfunction to Adora2a/Rap1-mediated VSMC ferroptosis.

    Evidence ADORA2A KO with rescue and HSL bisulfite sequencing in adipose (39976204); VSMC calcification model with PARP1/POLG genetic manipulation and RNA-seq (40401372)

    PMID:39976204 PMID:40401372

    Open questions at the time
    • Mechanism by which receptor signaling alters HSL promoter methylation not defined
    • Adora2a/Rap1-ferroptosis link is correlative within the calcification model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single cAMP-coupled receptor selects among its many downstream effector outcomes (cAMP/PKA, Stat3/Akt, PI3K/AKT, ERK/MYC, Rap1) across cell types remains unresolved.
  • No unified model linking ligand/cell context to effector choice
  • No structural data on G protein coupling or DRD2 heterodimer in the corpus
  • Most downstream cascades shown in single cell systems

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 1 GO:0060089 molecular transducer activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 2
Partners
DRD2

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 RDC8 (ADORA2A) encodes an adenosine A2 receptor that, when expressed in Y1 adrenal cells, dog thyrocytes, and Xenopus oocytes, constitutively activates adenylyl cyclase and the cAMP cascade; this activity was inhibited by adenosine deaminase and adenosine A2 receptor inhibitors. COS7 cells transfected with RDC8 cDNA acquired adenosine A2 receptor binding characteristics. Heterologous expression in multiple cell systems (Y1 adrenal cells, primary thyrocytes, Xenopus oocytes, COS7 cells); adenylyl cyclase activity assay; radioligand binding assay; pharmacological inhibition Biochemical and biophysical research communications High 2125216
1991 ADORA2A (RDC8) mRNA is expressed exclusively by enkephalin-containing medium spiny neurons in the rat striatum, and not by substance P-containing or cholinergic neurons, as determined by in situ hybridization histochemistry. In situ hybridization histochemistry combined with neurochemical phenotyping in rat caudate-putamen Journal of neurochemistry Medium 1713612
1996 The human ADORA2A gene consists of two exons interrupted by an intron of ~6.4 kb, and the gene is localized to chromosome 22q11.2 by fluorescent in situ hybridization and PCR analysis of human-hamster hybrid cell panels. Genomic cloning, sequence analysis, fluorescent in situ hybridization (FISH), PCR of human-hamster hybrid cell panels Biochemical and biophysical research communications Medium 8670304
2013 ADORA2A diplotype AA (homozygous haplotype A) is associated with higher ADORA2A mRNA and protein expression in both brain samples and lymphoblasts, and with higher cAMP production in lymphoblasts in response to adenosine, compared to BB diplotype, demonstrating that genetic variation functionally alters ADORA2A-mediated cAMP signaling. mRNA expression quantification in brain and lymphoblasts; Western blot for protein; cAMP assay in lymphoblasts stratified by diplotype Neurology Medium 23535492
2019 Inducible endothelial cell-specific deletion of Adora2a in mice protects against blood-brain barrier (BBB) breakdown, vascular inflammation, deficits in hippocampal synaptic plasticity, and cognitive impairment induced by high-fat diet/insulin resistance, establishing that Adora2a-mediated signaling in vascular endothelial cells directly mediates BBB disruption. Inducible conditional knockout (endothelial-specific Adora2a deletion); BBB permeability assays (sodium fluorescein, Evans blue); transmission electron microscopy of tight junctions; behavioral memory tests; electrophysiology (synaptic plasticity) The Journal of neuroscience High 30886019
2020 SNP rs2298383 in ADORA2A reduces ADORA2A mRNA transcript levels in peripheral blood mononuclear cells (PBMCs); the TT mutated genotype (lower ADORA2A expression) is associated with higher IFNG mRNA levels, suggesting that reduced A2AR signaling promotes a pro-inflammatory phenotype. RT-qPCR quantification of ADORA2A, IFNG, and IL4 mRNA in PBMCs stratified by rs2298383 genotype; correlation analysis International journal of molecular sciences Medium 32182774
2020 Adenosine activates ADORA2A to promote phosphorylation of Stat3 and Akt, resulting in increased Ang (angiogenin)-dependent angiogenesis in placental endothelial cells; ADORA2A overexpression or adenosine treatment reverses impaired angiogenesis in IUGR placenta in vitro and in vivo. In vitro angiogenesis assays; Matrigel plug assay in vivo; Western blot for phospho-Stat3 and phospho-Akt; ADORA2A overexpression and pharmacological manipulation in diet-induced IUGR mouse model Arteriosclerosis, thrombosis, and vascular biology Medium 37051927
2023 ADORA2A activation rewires proline metabolism via an ERK/MYC/PYCR cascade; increased proline synthesis promotes SIRT6/7-mediated deacetylation of H3K27, driving a neuroendocrine transcriptional program. Genetic ablation of Adora2a in mouse models inhibits neuroendocrine prostate and lung cancer development and prevents adenocarcinoma-to-neuroendocrine phenotypic transition. Genetically engineered mouse models (Adora2a ablation); RNA-seq; ChIP for H3K27ac/H3K27me3; metabolomics (proline); Western blot for ERK/MYC/PYCR/SIRT6/7; pharmacological ADORA2A blockade in vivo; in vitro signaling assays The Journal of clinical investigation High 38099497
2022 JMJD3-mediated H3K27me3 demethylation upregulates ADORA2A expression in macrophages (with C/EBPβ as an additional transcriptional enhancer of ADORA2A), and elevated ADORA2A inhibits caspase-3 cleavage to suppress macrophage apoptosis during LPS-induced acute lung injury. Chromatin immunoprecipitation (ChIP) for H3K27me3 at ADORA2A locus; JMJD3 inhibition/overexpression; ADORA2A knockdown; flow cytometry for apoptosis; TUNEL staining; Western blot for cleaved caspase-3; in vivo ALI mouse model Cell death discovery Medium 36456564
2020 ADORA2A is upregulated by ADORA2A methylation via miR-497/miR-195 downregulation in ossification of the posterior longitudinal ligament (OPLL); miR-195 and miR-497 directly target ADORA2A 3'UTR, and overexpression of these miRNAs inactivates the cAMP/PKA signaling pathway via ADORA2A downregulation to reduce osteogenic differentiation of PLL cells. Luciferase reporter assay (miRNA target validation); qRT-PCR and Western blot for ADORA2A, osteogenic markers; cAMP/PKA pathway analysis; bisulfite sequencing for promoter methylation; demethylation with 5-aza-2'-deoxycytidine The Biochemical journal Medium 32432317
2023 ADORA2A knockdown in colorectal carcinoma cell lines (SW620, HCT116) inhibits cell proliferation, migration, and invasion, reduces anti-apoptotic Bcl-2 expression, and increases Bax/cleaved caspase-3/cleaved caspase-9, while ADORA2A overexpression has the opposite effect; these effects are mediated through the PI3K/AKT signaling pathway. siRNA knockdown; plasmid overexpression; CCK-8, colony formation, wound healing, transwell assays; flow cytometry for apoptosis; Western blot for PI3K/AKT pathway proteins and apoptosis markers Scientific reports Medium 37945707
2025 PARP1-mediated PARylation of POLG leads to PARylation-dependent ubiquitination and downregulation of POLG, causing mitochondrial dysfunction and subsequent activation of Adora2a/Rap1 signaling, which drives vascular smooth muscle cell ferroptosis and vascular calcification. VSMC β-glycerophosphate calcification model; PARP1 knockdown (Parp1flox/flox Tagln-Cre+ mice); AAV9-sh-POLG injection; RNA-sequencing; Western blot for PARylation, ubiquitination, Adora2a, Rap1; mitochondrial function assays Arteriosclerosis, thrombosis, and vascular biology Medium 40401372
2025 AMP is converted to adenosine by ecto-5'-nucleotidase (CD73), and the resulting adenosine activates ADORA2A signaling to reduce DNA methylation of hormone-sensitive lipase (HSL) promoter, promoting HSL transcription and white fat lipolysis. This effect is partially eliminated in ADORA2A knockout mice and restored by ADORA2A re-expression. ADORA2A knockout mice; ADORA2A re-expression; bisulfite sequencing for HSL methylation; qRT-PCR for HSL transcription; CD73 inhibition; metabolic phenotyping on high-fat diet Advanced science Medium 39976204
2022 ADORA2A and DRD2 form heterodimers that co-localize in human retinal pigment epithelial (RPE) cells, as demonstrated by immunofluorescence and co-immunoprecipitation. Treatment with the ADORA2A antagonist 7-methylxanthine reduces ADORA2A expression and increases DRD2, ERK1/2, and phospho-ERK1/2 expression, indicating that ADORA2A inhibits the DRD2/ERK signaling pathway in these cells. Co-immunoprecipitation; immunofluorescence co-localization; siRNA knockdown of ADORA2A or DRD2; Western blot for ERK1/2, pERK1/2, DRD2; pharmacological treatment with 7-MX Ophthalmic research Medium 35724635
2024 Retina-specific AdoRA2a knockout (AdoRA2a-CKO) mice and pharmacological AdoRA2a antagonism with KW6002 both attenuate form-deprivation myopia progression in mice. AdoRA2a co-localizes with dopamine D2 receptor (Drd2) in the retina, and KW6002 has no inhibitory effect on myopia in Drd2-CKO mice, establishing that retinal AdoRA2a acts upstream of Drd2 to regulate myopia. Retina-specific conditional knockout (AdoRA2a-CKO); Drd2-CKO epistasis experiment; pharmacological antagonism (KW6002); refraction measurement; immunofluorescence co-localization; measurement of retinal adenosine and CD39/CD73 Investigative ophthalmology & visual science High 41533917
2024 Brain-specific RagA overexpression in transgenic mice upregulates ADORA2A expression in prefrontal cortex (confirmed by Western blot and RNA-seq), and the ADORA2A inhibitor istradefylline attenuates depressive-like behaviors in these mice, placing ADORA2A downstream of the RagA-p70S6K signaling pathway in depression-related behavior. RagA transgenic mice; RNA-seq of prefrontal cortex; Western blot for ADORA2A and phospho-p70S6K; behavioral assessments (depression-like tests); pharmacological ADORA2A inhibition with istradefylline; metabolomics Advanced science Medium 39373701
2024 Using a MiniPromoter derived from ADORA2A regulatory regions (Ple389), selective expression was achieved in medium spiny neurons of the striatum in mice and non-human primates, with high co-localization with dopamine D2 receptor-expressing MSNs and DARPP32, directly establishing that ADORA2A regulatory elements drive expression in D2-MSNs. rAAV-PHP.B delivery of MiniPromoter-reporter constructs; intravenous and intracerebroventricular injection in mice and NHP; immunofluorescence co-localization with D2R and DARPP32; histological analysis Scientific reports Medium 39548191
2023 Genistein activates ADORA2A in renal tubular cells (NRK-52E); ADORA2A overexpression mimics genistein's protective effects against hypoxia/reoxygenation-induced oxidative stress and apoptosis, while ADORA2A knockdown partially abrogates genistein's protection, establishing ADORA2A as the functional mediator of genistein's renoprotective effects. ADORA2A overexpression and siRNA knockdown in NRK-52E cells; H/R injury model; in vivo renal IR mouse model; cell proliferation, apoptosis, and oxidative stress assays Human & experimental toxicology Medium 36932924

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. Journal of neurochemistry 466 1713612
1990 RDC8 codes for an adenosine A2 receptor with physiological constitutive activity. Biochemical and biophysical research communications 259 2125216
2007 A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clinical pharmacology and therapeutics 183 17329997
2010 Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 141 20520601
2011 Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. European journal of neurology 87 21281405
2019 Endothelial Adora2a Activation Promotes Blood-Brain Barrier Breakdown and Cognitive Impairment in Mice with Diet-Induced Insulin Resistance. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 30886019
2012 Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation. British journal of pharmacology 76 21950736
2017 Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease. Neurobiology of aging 63 28941407
2013 ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus. Neurology 61 23535492
2009 Adenosine A(2A) receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder. European child & adolescent psychiatry 59 19565319
2009 A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease. Neurobiology of disease 57 19591938
2011 ADORA2A Gene variation, caffeine, and emotional processing: a multi-level interaction on startle reflex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 45 22012471
2020 Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players. Genes 43 32823594
2019 The Impact of Genetic Variations in ADORA2A in the Association between Caffeine Consumption and Sleep. Genes 41 31817803
2018 Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study. Purinergic signalling 40 30511252
2010 Age at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1. Neurogenetics 38 20512606
2016 Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2. Neuroepidemiology 37 28135712
1996 Characterization and chromosomal localization of the human A2a adenosine receptor gene: ADORA2A. Biochemical and biophysical research communications 32 8670304
2023 ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers. The Journal of clinical investigation 30 38099497
2016 Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX-treated pediatric patients affected by hematological malignancies. Pediatric blood & cancer 28 27399166
2012 Effects of ADORA2A gene variation and caffeine on prepulse inhibition: a multi-level risk model of anxiety. Progress in neuro-psychopharmacology & biological psychiatry 28 22940476
2019 Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia. Scientific reports 27 31324842
2015 Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients? Pharmacogenomics 26 25872644
2019 Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD. Progress in neuro-psychopharmacology & biological psychiatry 25 30946941
2021 ADORA2A-AS1 Restricts Hepatocellular Carcinoma Progression via Binding HuR and Repressing FSCN1/AKT Axis. Frontiers in oncology 22 34733789
2020 ADORA2A variation and adenosine A1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation. Translational psychiatry 19 33235193
2015 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. International journal of molecular sciences 19 25629231
2020 Coffee effectively attenuates impaired attention in ADORA2A C/C-allele carriers during chronic sleep restriction. Progress in neuro-psychopharmacology & biological psychiatry 18 33373678
2016 Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy. Neurochemical research 17 27038930
2012 Differential effects of ADORA2A gene variations in pre-attentive visual sensory memory subprocesses. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 17 22240468
2016 ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 16 27262510
2023 Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway. Arteriosclerosis, thrombosis, and vascular biology 15 37051927
2020 Genetic Polymorphism of ADORA2A Is Associated With the Risk of Epilepsy and Predisposition to Neurologic Comorbidity in Chinese Southern Children. Frontiers in neuroscience 15 33262686
2023 ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma. Scientific reports 14 37945707
2019 Association between ADORA2A gene polymorphisms and schizophrenia in the North Chinese Han population. Neuropsychiatric disease and treatment 14 31695381
2015 Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 14 26066465
2025 PARylation of POLG Mediated by PARP1 Accelerates Ferroptosis-Induced Vascular Calcification via Activating Adora2a/Rap1 Signaling. Arteriosclerosis, thrombosis, and vascular biology 13 40401372
2022 H3K27 tri-demethylase JMJD3 inhibits macrophage apoptosis by promoting ADORA2A in lipopolysaccharide-induced acute lung injury. Cell death discovery 13 36456564
2020 Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats. Journal of ethnopharmacology 13 32473369
2016 The association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypes. Sleep medicine 12 28215251
2022 Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer's Disease. International journal of molecular sciences 11 36430879
2020 Serum expression of EAAT2 and ADORA2A in patients with different degrees of Alzheimer's disease. European review for medical and pharmacological sciences 11 33275249
2024 Adora2A downregulation promotes caffeine neuroprotective effect against LPS-induced neuroinflammation in the hippocampus. Brain research 9 38494098
2024 Brain Specific RagA Overexpression Triggers Depressive-Like Behaviors in Mice via Activating ADORA2A Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39373701
2022 Knockdown of ADORA2A antisense RNA 1 inhibits cell proliferation and enhances imatinib sensitivity in chronic myeloid leukemia. Bioengineered 8 35034552
2025 Adenosine Monophosphate Improves Lipolysis in Obese Mice by Reducing DNA Methylation via ADORA2A Activation by Ecto-5'-Nucleotidase (CD73). Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39976204
2024 Effect of ADORA2A Gene Polymorphism and Acute Caffeine Supplementation on Hormonal Response to Resistance Exercise: A Double-Blind, Crossover, Placebo-Controlled Study. Nutrients 7 38931158
2023 The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake. Nutrients 7 37049474
2020 The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity. International journal of molecular sciences 7 32182774
2020 Analysis of association of ADORA2A and ADORA3 polymorphisms genotypes/haplotypes with efficacy and toxicity of methotrexate in patients with Rheumatoid arthritis. The pharmacogenomics journal 7 32448869
2020 The impact of single nucleotide polymorphisms in ADORA2A and ADORA3 genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study. International journal of rheumatic diseases 7 32969158
2023 Synergistic Anti-Tumor Effect of Toosendanin and Paclitaxel on Triple-Negative Breast Cancer via Regulating ADORA2A-EMT Related Signaling. Advanced biology 6 37401656
2021 Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms. Life (Basel, Switzerland) 6 34685481
2017 The plausible association of MTHFR and ADORA2A polymorphisms with nodules in rheumatoid arthritis patients treated with methotrexate. Pharmacogenetics and genomics 6 27846189
2020 Methylation-mediated down-regulation of microRNA-497-195 cluster confers osteogenic differentiation in ossification of the posterior longitudinal ligament of the spine via ADORA2A. The Biochemical journal 5 32432317
2019 ADORA2A Polymorphisms Influence Methotrexate Adverse Events in Rheumatoid Arthritis. The Israel Medical Association journal : IMAJ 5 31140226
2024 Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection. International journal of molecular sciences 4 38892324
2023 Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A. Genes 4 36833216
2023 Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy. Frontiers in pharmacology 4 37063258
2024 New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates. Scientific reports 3 39548191
2023 Genistein attenuates renal ischemia-reperfusion injury via ADORA2A pathway. Human & experimental toxicology 3 36932924
2023 Peripheral Expression of ADORA2A Is Increased and Is Correlated with Autism Spectrum Disorder Severity in a Sample of Turkish Children. Psychiatry and clinical psychopharmacology 3 38764528
2022 7-Methylxanthine Influences the Behavior of ADORA2A-DRD2 Heterodimers in Human Retinal Pigment Epithelial Cells. Ophthalmic research 3 35724635
2018 Adenosine A2A receptor gene polymorphisms (ADORA2A) are associated with maximal concentric contraction pain. Meta gene 3 37560748
2024 Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer. International journal of molecular sciences 2 38731962
2025 Caffeine exacerbates exercise-induced gut cell damage and is influenced by ADORA2A genotype but not CYP1A2 genotype: A preliminary study. Physiological reports 1 41261949
2024 Epigenetics and suicide: investigating altered H3K14ac unveiled differential expression in ADORA2A, B4GALT2 and MMP14. Epigenomics 1 38545853
2022 The Influence of ADORA2A on Levodopa-Induced Dyskinesia. Neurology India 1 35532631
2022 Can the Brazilian Caffeine Expectancy Questionnaires Differentiate the CYP1A2 and ADORA2A Gene Polymorphisms?-An Exploratory Study with Brazilian Athletes. Nutrients 1 36014860
2020 Impact of the Polymorphism rs5751876 of the Purinergic Receptor ADORA2A on Periprocedural Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention. Journal of atherosclerosis and thrombosis 1 33342966
2026 Inhibition of Retinal AdoRA2a Activity Attenuates Myopia Progression. Investigative ophthalmology & visual science 0 41533917
2025 Association study of ADORA2A gene polymorphisms with adverse drug reactions to valproic acid and oxcarbazepine in the treatment of children with epilepsy. Epilepsia 0 40751907
2025 Precision Targeting in Gastric Cancer: AI-Driven Discovery of MET, ADORA2A, CDK5R1, and ADORA1. Assay and drug development technologies 0 40932634

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