ADORA3

Summary

ADORA3 (adenosine A3 receptor, HGNC:268) is a protein-coding gene on chromosome 1p13.2, encoding Adenosine receptor A3 (P0DMS8). G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various physiological processes including immune regulation, cardioprotection and neuroprotection.

This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that are involved in a variety of intracellular signaling pathways and physiological functions. The receptor encoded by this gene mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Alternative splicing results in multiple transcript variants. This gene shares its 5’ terminal exon with some transcripts from overlapping GeneID:57413, which encodes an immunoglobulin domain-containing protein.

Source: NCBI Gene 140 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 21 total — 5 pathogenic
• Druggable target: yes — 417 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000677

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:268
Approved symbol	ADORA3
Name	adenosine A3 receptor
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	AD026, A3AR
Ensembl gene	ENSG00000282608
Ensembl biotype	protein_coding
OMIM	600445
Entrez	140

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000241356, ENST00000486342, ENST00000495493, ENST00000632535

RefSeq mRNA: 3 — MANE Select: NM_000677 NM_000677, NM_001302678, NM_001302679

CCDS: CCDS81358, CCDS839

Canonical transcript exons

ENST00000241356 — 2 exons

Exon	Start	End
ENSE00000826951	111499429	111500556
ENSE00000826952	111503005	111503633

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 87.13.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3295 / max 359.1829, expressed in 210 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13830	1.2189	205
13829	0.7224	186
13828	0.0712	29
13831	0.0394	17

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	87.13	gold quality
spinal cord	UBERON:0002240	85.47	gold quality
right adrenal gland cortex	UBERON:0035827	82.76	gold quality
right adrenal gland	UBERON:0001233	80.85	gold quality
left adrenal gland	UBERON:0001234	79.82	gold quality
left adrenal gland cortex	UBERON:0035825	78.90	gold quality
adrenal cortex	UBERON:0001235	78.89	gold quality
inferior vagus X ganglion	UBERON:0005363	78.51	silver quality
mucosa of transverse colon	UBERON:0004991	77.51	gold quality
adrenal gland	UBERON:0002369	76.96	gold quality
substantia nigra	UBERON:0002038	76.79	gold quality
descending thoracic aorta	UBERON:0002345	76.63	gold quality
gall bladder	UBERON:0002110	76.56	gold quality
midbrain	UBERON:0001891	76.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.92	gold quality
medial globus pallidus	UBERON:0002477	75.53	gold quality
subthalamic nucleus	UBERON:0001906	75.17	silver quality
rectum	UBERON:0001052	75.09	gold quality
right coronary artery	UBERON:0001625	74.68	gold quality
left coronary artery	UBERON:0001626	74.63	gold quality
decidua	UBERON:0002450	74.46	silver quality
coronary artery	UBERON:0001621	74.21	gold quality
layer of synovial tissue	UBERON:0007616	74.13	gold quality
peripheral nervous system	UBERON:0000010	74.07	gold quality
tibial nerve	UBERON:0001323	74.07	gold quality
transverse colon	UBERON:0001157	74.02	gold quality
globus pallidus	UBERON:0001875	74.01	gold quality
small intestine	UBERON:0002108	73.63	gold quality
thoracic aorta	UBERON:0001515	73.56	gold quality
amniotic fluid	UBERON:0000173	73.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, RELA, TCF3

miRNA regulators (miRDB)

64 targeting ADORA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952

Literature-anchored findings (GeneRIF, showing 40)

• identification of residues in ligand recognition and activation (PMID:11891221)
• involvement in adenosine inhibition of tissue factor expression by LPS-stimulated human monocytes (PMID:12152652)
• adenosine triggers a survival signal via A3 receptor activation and it kills the cell through A2A receptor inducing a signaling pathway that involves protein kinase C and mitogen-activated protein kinases. (PMID:12406340)
• A(3) receptors, in astrocytoma cells, are regulated after short- and long-term agonist exposure. (PMID:12435805)
• Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. (PMID:12600879)
• using a rhodopsin-based molecular model of the A(3)AR to suggest multiple binding modes of the allosteric modulators. (PMID:12695530)
• how RhoA activates phospholipase D to achieve the anti-ischemic effect of adenosine A3 receptors (PMID:14688204)
• an in-depth investigation of A3 receptors in human lymphocytes and demonstrate that, under activating conditions, they are up-regulated and may contribute to the effects triggered by adenosine. (PMID:14978250)
• effects of an A3AR agonist, IB-MECA, on the cell growth of human breast cancer cell lines suggest that the inhibitory effect of on the growth of human breast cancer cell lines is mediated through activation of A3 adenosine receptor. (PMID:15147729)
• A(3)AR is expressed in tumors and may have a role in disease progression (PMID:15240539)
• Elevated expression of A3 adenosine receptors is associated with colorectal cancer (PMID:15355922)
• biophysical analysis of the effect of surfactants on human adenosine a3 receptor (PMID:15849244)
• A3 receptor stimulation activates p44/p42 and p38 mitogen-activated protein kinases, which are required for A3-induced increase of HIF-1alpha and Ang-2 (PMID:16242072)
• These data suggest that hypertonic saline upregulates polymorphonuclear neutrophil degranulation via ATP release and positive feedback through P2 and A3 receptors. (PMID:16282197)
• Modulation of the adenosine A3 receptor on cord blood mononuclear cells polarizes toll- like receptor-mediated cytokine production during the perinatal period and may thereby modulate the newborn innate and adaptive immune responses. (PMID:16849509)
• ATP release and autocrine feedback through P2Y2 and A3 receptors provide signal amplification, controlling gradient sensing and migration of neutrophils (PMID:17170310)
• Overexpression of A3AR was found in PBMC of RA patients. Receptor upregulation was induced by inflammatory cytokines controlling the expression of the A3AR transcription factor NF-kappaB (PMID:17216675)
• in colon cancer cell lines endogenous adenosine, through the interaction with A(3) receptors, mediates a tonic proliferative effect (PMID:17348028)
• Genetic variants in the adenosine A1/A3 receptor genes may predict the heart’s response to ischemia or injury and might also influence an individual’s response to adenosine therapy. (PMID:17728764)
• our findings revealed the role of adenosine receptors in breast cancer cell lines on growth modulation role of A3 and functional form of A2B, although its involvement in cell growth modulation was not seen (PMID:18351132)
• The A3 adenosine receptor is highly expressed in hepatocellular carcinoma (HCC)patients and might be a novel targeted therapy to treat HCC. (PMID:18636149)
• Activation of the adenosine-A3 receptor stimulates matrix metalloproteinase-9 secretion by macrophages. (PMID:18653544)
• when PBMC were stimulated with IFN-alpha, adenosine did not decrease, but synergistically increased, the IFN-gamma production of NK cells. This effect was also mediated mainly via the A(3) receptor (PMID:19095736)
• NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation. (PMID:19426966)
• Data suggest that adenosine receptor modulation may be useful for refining the use of chemotherapeutic drugs to treat human cancer more effectively. (PMID:19794965)
• Studies indicate that adenosine mediates its actions by means of activation of specifiic G protein-coupled receptors, for which 4 subbtypes: A1R, A2AR, A2BR and A3R have (PMID:19883624)
• we show that A3 adenosine receptor/Gi3 play important roles in human mast cells responses initiated on contact with activated T cells. (PMID:20190146)
• results suggest that the high-transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper-reactivity to aspirin, leading to the clinical presentation of aspirin-induced urticaria. (PMID:20716228)
• testicular mouse A3Ri2 and human A3Ri3 adenosine receptors have roles in sperm function (PMID:20732875)
• ADORA3 was expressed weakly in the cytoplasm of retinal pigment epithelium. (PMID:21542986)
• single-nucleotide polymorphism (SNP) I248L (reference SNP ID: rs35511654) located in the A3R gene is associated with coronary heart disease (PMID:21675873)
• This study provides new insight into the spatial and temporal specificity of drug action that can be provided by allosteric modulation across a GPCR homodimeric interface. (PMID:21715680)
• control of prostate cancer cell growth through A3 adenosine receptor activation. (PMID:21830157)
• A3 receptor expression on the surface of PMNs is upregulated by injury, and increased expression levels are associated with greater injury severity and hypovolemic shock. (PMID:21841534)
• Data show that A2A and A3 adenosine receptor density inversely correlated with Disease Activity Score in 28 or 44 joints (DAS28 or DAS) suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation. (PMID:22146575)
• adenosine stimulates human endothelial progenitor cells migration by activating AA and A receptors and provides evidence to support a role of adenosine in modulating angiogenic capacity of hEPC (PMID:22217884)
• Inactivation of the ADORA3 receptor prevents the CXCL16 effect of neuroprotection against excitotoxic damage. (PMID:22378888)
• There is differential expression of receptors in rheumatoid synovial tissue such that ADORA3 is expressed at significantly higher levels (PMID:22682496)
• Activation of smooth muscle adenosine A(3) receptors increase proliferation of human coronary smooth cells. (PMID:22906537)
• A3Rs play a role in neutrophil migration and disrupting this function has the potential to adversely affect innate immune responses. (PMID:23027555)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000026246
danio_rerio	adora3a.1	ENSDARG00000044061
mus_musculus	Adora3	ENSMUSG00000000562
rattus_norvegicus	Adora3	ENSRNOG00000015788
drosophila_melanogaster	AdoR	FBGN0039747

Paralogs (3): ADORA2A (ENSG00000128271), ADORA1 (ENSG00000163485), ADORA2B (ENSG00000170425)

Protein

Protein identifiers

Adenosine receptor A3 — P0DMS8 (reviewed: P0DMS8)

All UniProt accessions (2): P0DMS8, A0A0J9YWR0

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various physiological processes including immune regulation, cardioprotection and neuroprotection. Also acts as a receptor for adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification, which are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs): activated by N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A). Preferentially couples to the inhibitory G protein (Gi), leading to the suppression of adenylate cyclase activity and a reduction in intracellular cyclic AMP levels. Upon adenosine binding, mediates cardioprotection in cardiomyocytes through anti-apoptotic effects primarily via the ERK1/2 pathway as well as the PI3K pathway. In the central nervous system, participates in the modulation of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. In lung mast cells, receptor activation contributes to the type I allergic response by facilitating mast cell degranulation and histamine release. Highly expressed in inflammatory cells such as neutrophils and mast cells, inhibits neutrophil degranulation and reduces superoxide production, thereby modulating inflammatory responses. Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the lung and bone. Expressed at lower levels in osteosarcoma tissues (at protein level).

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P0DMS8-1	2, A3AR i2, A3AR	yes
P0DMS9-2	1, TMIGD3 i1, A3AR i1
P0DMS9-1	3, TMIGD3 i3, A3AR i3

RefSeq proteins (3): NP_000668, NP_001289607, NP_001289608 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000466	Adeno_A3_rcpt	Family
IPR001634	Adenosn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (64 total): helix 16, mutagenesis site 11, topological domain 8, transmembrane region 7, binding site 6, turn 4, glycosylation site 3, sequence variant 3, sequence conflict 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8X17	ELECTRON MICROSCOPY	3.19
9EHS	ELECTRON MICROSCOPY	3.2
8X16	ELECTRON MICROSCOPY	3.29
9EBH	ELECTRON MICROSCOPY	3.6
9EBI	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMS8-F1	91.51	0.85

Antibody-complex structures (SAbDab): 4 — 8X16, 8X17, 9EBH, 9EBI

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 168; 169; 250; 250; 272; 272

Post-translational modifications (1): 303

Disulfide bonds (1): 83–166

Glycosylation sites (3): 3, 4, 12

Mutagenesis-validated functional residues (11):

Position	Phenotype
15	abolished receptor activation upon ligand binding.
73	slightly decreased activation by adenosine.
95	decreased activation by adenosine.
169	abolished activation by adenosine and n(6)-methyladenosine (m6a).
169	strongly decreased activation by adenosines containing n(6)-methylated adenine (m6a).
181	abolished receptor activation upon ligand binding.
247	abolished receptor activation upon ligand binding.
253	decreased activation by n(6)-methyladenosine (m6a).
264	decreased activation by n(6)-methyladenosine (m6a).
265	slightly decreased activation by adenosine.
271	decreased activation by adenosine.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-417973	Adenosine P1 receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-418038	Nucleotide-like (purinergic) receptors
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 246 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_MAST_CELL_ACTIVATION

GO Biological Process (12): G protein-coupled adenosine receptor signaling pathway (GO:0001973), inflammatory response (GO:0006954), signal transduction (GO:0007165), activation of adenylate cyclase activity (GO:0007190), regulation of heart contraction (GO:0008016), negative regulation of cell population proliferation (GO:0008285), response to wounding (GO:0009611), regulation of norepinephrine secretion (GO:0014061), negative regulation of cell migration (GO:0030336), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), presynaptic modulation of chemical synaptic transmission (GO:0099171), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (2): G protein-coupled adenosine receptor activity (GO:0001609), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (6): plasma membrane (GO:0005886), dendrite (GO:0030425), presynaptic membrane (GO:0042734), synapse (GO:0045202), Schaffer collateral - CA1 synapse (GO:0098685), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Nucleotide-like (purinergic) receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	2
G protein-coupled receptor activity	2
G protein-coupled purinergic receptor signaling pathway	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of adenylate cyclase activity	1
heart contraction	1
regulation of blood circulation	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to stress	1
norepinephrine secretion	1
regulation of catecholamine secretion	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
modulation of chemical synaptic transmission	1
signal transduction	1
G protein-coupled adenosine receptor signaling pathway	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
synaptic membrane	1
cell junction	1
synapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADORA3	LTBP3	Q9NS15	655
ADORA3	LTBP2	Q14767	654
ADORA3	LTBP1	P22064	651
ADORA3	ADA	P00813	650
ADORA3	P2RY2	P41231	635
ADORA3	ADK	P55263	607
ADORA3	P2RY13	Q9BPV8	602
ADORA3	ENTPD1	P49961	585
ADORA3	NT5E	P21589	571
ADORA3	P2RY10	O00398	539
ADORA3	C5AR1	P21730	512
ADORA3	P2RY14	Q15391	492
ADORA3	LOXL1	Q08397	490
ADORA3	EPB41	P11171	479
ADORA3	SLC29A1	Q99808	477

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O02667, O13076, O77621, P0C0L6, P0DMS8, P25099, P28190, P28647, P29275, P29276, P35342, P35382, P47745, P47936, P49892, P79945, Q0VC81, Q1LZD0, Q28309, Q32ZE2, Q56H79, Q5QD05, Q5QD06, Q5QD07, Q5QD08, Q5QD10, Q5QD11, Q5QD12, Q5QD13, Q5QD21, Q5RF57, Q5W8W0, Q60612, Q60614, Q61618, Q6W3F4, Q6W5P4, Q7TQP3, Q8BZP8, Q923X5

Diamond homologs: B2RPY5, B3DM66, O02664, O13076, O19014, O19032, O19091, O77408, O77621, O77713, O77721, P08908, P0DMS8, P16395, P18089, P18130, P19327, P21917, P22270, P30542, P30552, P32229, P32239, P32250, P34970, P43657, P46627, P49220, P49684, P97718, Q09388, Q0EAB6, Q18904, Q24563, Q25321, Q25322, Q25414, Q2YDN1, Q4G072, Q4LBB6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ADORA3	“up-regulates activity”	GNAI1	binding
ADORA3	“up-regulates activity”	GNAI3	binding
adenosine	“up-regulates activity”	ADORA3	“chemical activation”
adenosine	“up-regulates activity”	ADORA3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1527171	GRCh37/hg19 1p21.3-13.2(chr1:95046805-114714931)	Pathogenic
2424614	NC_000001.10:g.(?111145905)(114454813_?)del	Pathogenic
2685555	GRCh37/hg19 1p13.3-13.2(chr1:109483388-112293512)x1	Pathogenic
2685577	GRCh37/hg19 1p13.3-13.1(chr1:110066946-116672408)x1	Pathogenic
688916	GRCh37/hg19 1p13.3-13.2(chr1:110994179-112360446)x1	Pathogenic

SpliceAI

202 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111503018:TG:T	donor_gain	0.9900
1:111502999:GGCTA:G	donor_loss	0.9600
1:111503000:GCTA:G	donor_loss	0.9600
1:111503001:CTACC:C	donor_loss	0.9600
1:111503002:TAC:T	donor_loss	0.9600
1:111503003:ACCTG:A	donor_loss	0.9600
1:111503004:C:G	donor_loss	0.9600
1:111503005:C:A	donor_loss	0.9500
1:111503019:G:T	donor_gain	0.9300
1:111503006:TG:T	donor_gain	0.9200
1:111502917:CATTT:C	donor_gain	0.8900
1:111503243:TG:T	donor_gain	0.8200
1:111502881:ATTGC:A	donor_gain	0.8100
1:111502881:ATTG:A	donor_gain	0.7700
1:111499500:A:AC	donor_gain	0.7600
1:111500220:AG:A	donor_gain	0.7400
1:111500221:G:C	donor_gain	0.7400
1:111503358:G:A	donor_gain	0.7200
1:111499950:C:CT	donor_gain	0.7000
1:111499951:T:TT	donor_gain	0.7000
1:111502998:AGGCT:A	donor_loss	0.6900
1:111503007:G:T	donor_gain	0.6800
1:111502928:A:AC	donor_gain	0.6700
1:111503004:CCTGA:C	donor_gain	0.6600
1:111501191:C:CT	donor_gain	0.6500
1:111501192:T:TT	donor_gain	0.6500
1:111503008:A:AC	donor_gain	0.6500
1:111503009:C:CC	donor_gain	0.6500
1:111502929:A:C	donor_gain	0.6300
1:111499957:G:C	donor_gain	0.6100

AlphaMissense

2077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:111503182:T:A	D58V	0.999
1:111503182:T:G	D58A	0.999
1:111503183:C:G	D58H	0.999
1:111500190:A:C	F239L	0.998
1:111500190:A:T	F239L	0.998
1:111500192:A:G	F239L	0.998
1:111503032:C:G	R108P	0.998
1:111503181:G:C	D58E	0.998
1:111503181:G:T	D58E	0.998
1:111503182:T:C	D58G	0.998
1:111503265:G:C	N30K	0.998
1:111503265:G:T	N30K	0.998
1:111500180:A:G	W243R	0.997
1:111500180:A:T	W243R	0.997
1:111500504:A:G	W135R	0.997
1:111500504:A:T	W135R	0.997
1:111500073:G:C	N278K	0.996
1:111500073:G:T	N278K	0.996
1:111503171:C:G	G62R	0.996
1:111503171:C:T	G62R	0.996
1:111503194:A:G	L54P	0.996
1:111503270:C:G	G29R	0.996
1:111500085:G:C	N274K	0.995
1:111500085:G:T	N274K	0.995
1:111500173:G:C	P245R	0.995
1:111500462:A:G	W149R	0.995
1:111500462:A:T	W149R	0.995
1:111500483:C:G	G142R	0.995
1:111500483:C:T	G142R	0.995
1:111503171:C:A	G62W	0.995

dbSNP variants (sampled 300 via entrez): RS1000177935 (1:111501179 G>A,T), RS1000224683 (1:111502481 AAT>A,AATAT), RS1000544344 (1:111502806 T>C), RS1001779681 (1:111501789 C>G,T), RS1001817453 (1:111504153 G>A,C), RS1002187910 (1:111504389 C>A,T), RS1002229836 (1:111499262 A>C,G), RS1002421860 (1:111499046 G>A,C), RS1004012442 (1:111505551 C>T), RS1005427736 (1:111499581 T>G), RS1006230910 (1:111502046 T>A,G), RS1006304393 (1:111501710 A>G), RS1006363170 (1:111501776 A>C), RS1006568275 (1:111503694 C>A), RS1007146191 (1:111501373 A>C)

Disease associations

OMIM: gene MIM:600445 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_248	Obesity-related traits	7.000000e-06
GCST001762_764	Obesity-related traits	7.000000e-06
GCST001762_786	Obesity-related traits	7.000000e-06
GCST006402_4	Energy intake	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0009374	energy intake measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095195 (SELECTIVITY GROUP), CHEMBL2095213 (SELECTIVITY GROUP), CHEMBL2095234 (SELECTIVITY GROUP), CHEMBL2111329 (PROTEIN FAMILY), CHEMBL256 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

417 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,067,760 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL1095	ETHOTOIN	4	5,435
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL110691	CHLORMADINONE ACETATE	4	9,747
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL113	CAFFEINE	4	200,591
CHEMBL11359	CISPLATIN	4
CHEMBL1138	EZETIMIBE	4
CHEMBL1161	MOMETASONE FUROATE	4
CHEMBL1171837	PONATINIB	4
CHEMBL118	CELECOXIB	4
CHEMBL1198857	VILANTEROL	4
CHEMBL1200384	BETAMETHASONE DIPROPIONATE	4
CHEMBL1200430	ESTRADIOL ACETATE	4
CHEMBL1200438	TIOCONAZOLE	4
CHEMBL1200500	BECLOMETHASONE DIPROPIONATE	4
CHEMBL1200515	DESERPIDINE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3394	ADORA3, TMIGD3		0.00	0
rs2298191	ADORA3, TMIGD3		0.00	0
rs3393	ADORA3, TMIGD3		0.00	0
rs35511654	ADORA3, TMIGD3		0.00	0
rs1544223	ADORA3, TMIGD3		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adenosine receptors

Most potent curated ligand interactions (102 total), top 25:

Ligand	Action	Affinity	Parameter
KF26777	Antagonist	9.7	pKi
MRS3558	Agonist	9.54	pKi
(R,S)-PHPNECA	Full agonist	9.4	pKi
2-phenylethylyl-adenosine derivative	Agonist	9.36	pKi
PSB-10	Antagonist	9.36	pKi
MRE 3010F20	Antagonist	9.3	pKi
MRS7799	Antagonist	9.26	pKd
piclidenoson	Full agonist	9.2	pKi
MRS1220	Antagonist	9.2	pKi
[125I]AB-MECA	Full agonist	9.1	pKd
[3H]MRE 3008F20	Antagonist	9.1	pKd
[3H]HEMADO	Full agonist	9.0	pKd
HEMADO	Agonist	8.96	pKi
Cl-IB-MECA	Full agonist	8.9	pKi
MRS5980	Full agonist	8.71	pEC50
MRS5151	Agonist	8.62	pKi
compound 6c [PMID: 34435786]	Agonist	8.62	pKi
2-hexynyl-NECA	Full agonist	8.6	pKi
MRS1177	Antagonist	8.5	pKi
MRS5698	Agonist	8.5	pKi
NECA	Full agonist	8.4	pKi
VUF5574	Antagonist	8.39	pKi
PSB-11	Antagonist	8.31	pKd
[3H]PSB-11	Antagonist	8.3	pKd
CP608,039	Agonist	8.24	pKi

Binding affinities (BindingDB)

359 measured of 444 human assays (459 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-(3-Cyanophenyl)-5-pyrazolo[1,5-a]pyridin-5-yl-thiazol-2-yl]morpholine-4-carboxamide	KI	0.2 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-(3-methylbenzimidazol-5-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	0.3 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-imidazo[1,2-a]pyridin-6-yl-thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	0.3 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	KI	0.35 nM
N-[4-(3-Cyanophenyl)-5-(3-methylimidazo[1,2-a]pyridin-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	0.4 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
1-(3-chlorophenyl)-3-[2-(furan-2-yl)-8-propyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]urea	KI	0.48 nM
2-[4-(ethylsulfanyl)-1H-1,3-benzodiazol-2-yl]quinoxaline	KI	0.5 nM
N-[4-(3-Cyanophenyl)-5-(7-methyl-1H-indazol-5-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	0.5 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
MRE 3055F20	KI	0.53 nM
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (3)	KI	0.71 nM
1-(8-butyl-2-(furan-2-yl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-3-phenylurea	KI	0.93 nM
[(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl nitrate	KI	0.97 nM	US-8470800: Method of reducing intraocular pressure in humans
N-[4-(3-Cyanophenyl)-5-(7-methyl-3H-benzotriazol-5-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	1 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	1 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	1 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[4-(3-Cyanophenyl)-5-(3,8-dimethylimidazo[1,2-a]pyridin-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	1 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
MRE 3048F20	KI	1.2 nM
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (4)	KI	1.4 nM
MRE 3046F20	KI	1.5 nM
(S)-(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	IC50	1.55 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
N-[5-(1,3-benzoxazol-6-yl)-4-(3-cyanophenyl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	1.6 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
6R, (R)-PHPNECA	KI	1.9 nM
N-[4-(3-Cyanophenyl)-5-(4-methyl-1H-indazol-6-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	2 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (5)	KI	2.1 nM
6S, (S)-PHPNECA	KI	2.1 nM
(1R,3S,4R)-2,3-dihydroxy-N-methyl-4-[6-(methylamino)-2-[2-(1H-pyrazol-5-yl)ethynyl]purin-9-yl]bicyclo[3.1.0]hexane-1-carboxamide	KI	2.23 nM	US-10577368: A3 adenosine receptor agonists
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (7)	KI	2.3 nM
[(2R,3S,4R,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl nitrate	KI	2.63 nM	US-8470800: Method of reducing intraocular pressure in humans
cyclopenta-1,3-diene;(1R,3S,4R)-4-[2-(2-cyclopenta-1,3-dien-1-ylethynyl)-6-(methylamino)purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide;iron(2+)	KI	2.68 nM	US-10577368: A3 adenosine receptor agonists
R,S-PHPNECA	KI	2.7 nM
cyclopenta-1,3-diene;(1R,3S,4R)-4-[2-(4-cyclopenta-1,3-dien-1-yltriazol-1-yl)-6-(methylamino)purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide;iron(2+)	KI	3.09 nM	US-10577368: A3 adenosine receptor agonists
5-[6-Amino-2-(3-hydroxy-but-1-ynyl)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide	KI	3.3 nM
10-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	KI	3.5 nM	US-9227979: Fluorescent antagonists of the A3 adenosine receptor
N-[4-(3-Cyanophenyl)-5-(1-methylpyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	4 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
[(2S,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methanesulfonate	KI	4.05 nM	US-8609833: Purine derivatives as adenosine A1 receptor agonists and methods of use thereof
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (6)	KI	5.5 nM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl nitrate	KI	5.79 nM	US-8609833: Purine derivatives as adenosine A1 receptor agonists and methods of use thereof
(1S,2R,3S,4R,5S)-6-(3-Chlorobenzylamino)-(2-(6-(1-(adamantyl)-1H-1,2,3-triazol-4-yl)hex-1-ynyl)-9H-purin-9-yl)-2’,3’-dihydroxybicyclo[3.1.0]hexane-1’-carboxylic acid N-methylamide	KI	6.5 nM
[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl nitrate	KI	7 nM	US-8609833: Purine derivatives as adenosine A1 receptor agonists and methods of use thereof
Adenosine analog, 6	KI	7 nM
2-substituted NECA derivatives, 8	KI	8 nM
N-[9-(ortho-fluorobenzyl)-2-phenyl-9H-8-azapurin-6-yl]-amides (2)	KI	9.2 nM
5-[6-Amino-2-(3-hydroxy-3-phenyl-but-1-ynyl)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide	KI	9.4 nM
MPC-NECA	KI	10 nM
(1R,2R,3S,5S)-5-[2-chloro-6-[[2-(2-fluoroethoxy)phenyl]methylamino]purin-9-yl]bicyclo[3.1.0]hexane-2,3-diol	KI	10.3 nM	US-9181253: Adenosine receptor agonists, partial agonists, and antagonists
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolan-2-yl]methyl nitrate	KI	10.6 nM	US-8470800: Method of reducing intraocular pressure in humans
5-(6-Amino-2-thiazol-2-ylethynyl-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide	KI	12 nM
Adenosine analog, 11	KI	12.8 nM
N-[4-(3-Cyanophenyl)-5-(6-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)thiazol-2-yl]-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide	KI	14 nM	US-20250243194: ANTAGONIST OF ADENOSINE RECEPTORS
NSC_448222	KI	14 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL118923
11.00	Ki	0.01	nM	CHEMBL332091
11.00	Ki	0.01	nM	CHEMBL1771603
10.85	Ki	0.014	nM	CHEMBL118923
10.84	IC50	0.01445	nM	IB-MECA
10.79	EC50	0.01622	nM	CHEMBL5558289
10.67	IC50	0.02138	nM	IB-MECA
10.64	IC50	0.02291	nM	IB-MECA
10.57	Ki	0.027	nM	CHEMBL3754229
10.40	Ki	0.04	nM	CHEMBL332091
10.34	Ki	0.046	nM	CHEMBL332091
10.31	IC50	0.04898	nM	IB-MECA
10.29	IC50	0.05129	nM	IB-MECA
10.21	IC50	0.061	nM	CHEMBL1098108
10.20	EC50	0.0631	nM	CHEMBL4464176
10.11	Kd	0.07762	nM	CHEMBL88147
10.10	Ki	0.08	nM	IB-MECA
10.01	IC50	0.09772	nM	CHEMBL88147
10.01	Kd	0.09772	nM	CHEMBL88147
9.97	Ki	0.108	nM	CHEMBL1091268
9.96	IC50	0.11	nM	CHEMBL3754229
9.96	Ki	0.11	nM	CHEMBL340868
9.94	Ki	0.1148	nM	CHEMBL5201810
9.94	Ki	0.1148	nM	CHEMBL88147
9.93	EC50	0.1175	nM	NECA
9.89	IC50	0.13	nM	IB-MECA
9.89	Ki	0.13	nM	IB-MECA
9.85	Ki	0.14	nM	CHEMBL145767
9.85	Ki	0.14	nM	CHEMBL348975
9.85	Ki	0.14	nM	CHEMBL144979
9.85	Ki	0.14	nM	CHEMBL209992
9.85	Ki	0.1413	nM	CHEMBL145767
9.85	Ki	0.1413	nM	CHEMBL348975
9.82	Ki	0.15	nM	CHEMBL168018
9.82	Ki	0.1514	nM	CHEMBL168018
9.80	Ki	0.16	nM	CHEMBL324735
9.80	Kd	0.1585	nM	CHEMBL2181968
9.80	IC50	0.16	nM	CHEMBL2181968
9.80	EC50	0.1585	nM	CHEMBL4464176
9.80	Ki	0.1585	nM	CHEMBL324735
9.80	Ki	0.16	nM	CHEMBL1834703
9.77	IC50	0.17	nM	CHEMBL4128926
9.74	Ki	0.18	nM	CHEMBL331111
9.74	Ki	0.1799	nM	CHEMBL352796
9.74	Ki	0.18	nM	CHEMBL352796
9.74	Ki	0.182	nM	CHEMBL352796
9.74	Ki	0.18	nM	CHEMBL1098108
9.72	Ki	0.19	nM	CHEMBL141550
9.72	Ki	0.19	nM	CHEMBL133591
9.70	Ki	0.2	nM	CHEMBL329791

PubChem BioAssay actives

2970 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2-amino-4,5-dihydrobenzo[e][1,3]benzothiazol-7-yl) acetate;hydroiodide	33505: AE maximal score at Adenosine A3 receptor	ec50	<0.0001	uM
(2S,3S,4R,5R)-3,4-dihydroxy-5-[6-[(3-iodophenyl)methylamino]purin-9-yl]-N-methyloxolane-2-carboxamide	1526077: Agonist activity at wild type human A3 receptor stably expressed in Flp-In CHO cells cotransfected with pOG44 assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by LANCE assay	ic50	<0.0001	uM
4-methoxy-N-(2-phenyl-5-thiophen-2-ylpyrazolo[4,3-d]pyrimidin-7-yl)benzamide	1271553: Displacement of [125I]AB-MECA at human A3A receptor expressed in CHO cell membrane after 60 mins by scintillation counting method	ki	<0.0001	uM
1-[9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-3-(4-methoxyphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0001	uM
1-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-methylphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0001	uM
1-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-phenylurea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0001	uM
1-[4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-yl]-3-(4-methoxyphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0001	uM
5-butyl-8-(4-methoxyphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34283: Binding affinity for human adenosine A3 receptor expressed in HEK293 cells	ic50	0.0001	uM
(1S,2R,3S,4R,5S)-4-[2-chloro-6-(3-chloro-N-methylanilino)purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide	1573519: Agonist activity at adenosine A3 receptor (unknown origin) expressed in serum starved CHO cells assessed as increase in cell survival after 24 hrs by propidium iodide staining-based assay	ec50	0.0001	uM
(2R,3R,4R,5S)-4-amino-2-[6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolan-3-ol	34581: Binding affinity at Mutant (H272E) human adenosine A3 receptor expressed in COS-7 cells	ki	0.0002	uM
1-[9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-3-(3-chlorophenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
(2R,3R,4S,5R)-2-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	34120: Displacement of [125 I]AB-MECA from adenosine A3 receptor in bovine cortical membranes with 20 nM DPCPX	ki	0.0002	uM
(2R,3R,4S,5R)-2-[6-(ethylamino)-2-[(3S)-3-hydroxy-3-phenylprop-1-ynyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	34576: Binding affinity against Human recombinant Adenosine A3 receptor stably transfected in CHO cells using [3H]NECA as radioligand	ki	0.0002	uM
1-(1,3-benzodioxol-5-yl)-3-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
1-[11-butyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-phenylurea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
1-(4-chlorophenyl)-3-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[2-(2-phenylethylamino)-6-(trifluoromethyl)purin-9-yl]oxolane-3,4-diol	706377: Antagonist activity at human adenosine A3 receptor expressed in CHO cells assessed as blockade of Cl-IB-MECA-mediated inhibition of forskolin-stimulated [3H]cAMP accumulation by scintillation counter	ic50	0.0002	uM
1-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-phenylurea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
1-[11-butyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-methylphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0002	uM
2-(4-bromophenyl)-4-propyl-8,9-dihydro-7H-imidazo[2,1-f]purin-5-one	706384: Displacement of [125I]I-AB-MECA from human recombinant adenosine A3 receptor expressed in CHO cells after 60 mins by gamma counter	ki	0.0002	uM
5-butyl-8-(3-methoxyphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0002	uM
8-phenyl-5-propyl-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0002	uM
5-butyl-8-(4-ethoxyphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0002	uM
1-(4-chlorophenyl)-3-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(4-fluorophenyl)-3-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-[11-butyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-methoxyphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(4-chlorophenyl)-3-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-methylphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(2-methoxyphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(1,3-benzodioxol-5-yl)-3-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(4-fluorophenyl)-3-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(2-chlorophenyl)-3-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
1-(1,3-benzodioxol-5-yl)-3-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0003	uM
(1S,2R,3S,4R,5S)-4-[2-chloro-6-[(3-chlorophenyl)methylamino]purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide	239092: Inhibition of [125I]-AB-MECA binding to human Adenosine A3 receptor expressed in CHO cells	ki	0.0003	uM
1-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-pyridin-2-ylurea	261449: Displacement of [3H]MRE3008-F20 from human adenosine A3 receptor expressed in HEK293 cells	ki	0.0003	uM
5-butyl-8-(4-methylphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-butyl-8-(4-fluorophenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-butyl-8-(4-propoxyphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-pentyl-8-phenyl-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-butyl-8-phenyl-1H-[1,2,4]triazolo[5,1-f]purine	34283: Binding affinity for human adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-butyl-8-(3-methylphenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
5-butyl-8-(2-chlorophenyl)-1H-[1,2,4]triazolo[5,1-f]purine	34284: Displacement of [125I]AB-MECA binding to human Adenosine A3 receptor expressed in HEK293 cells	ic50	0.0003	uM
(2R,3R,4S,5R)-2-[6-[(3-bromophenyl)methylamino]-2-chloropurin-9-yl]-5-(2-ethyltetrazol-5-yl)oxolane-3,4-diol	1483034: Displacement of [3H]HEMADO from recombinant human adenosine A3A receptor expressed in CHO cell membranes after 3 hrs by microbeta scintillation counting	ki	0.0003	uM
(2R,3R,4S,5R)-2-[2-chloro-6-(cyclopropylmethylamino)purin-9-yl]-5-(2-ethyltetrazol-5-yl)oxolane-3,4-diol	1483034: Displacement of [3H]HEMADO from recombinant human adenosine A3A receptor expressed in CHO cell membranes after 3 hrs by microbeta scintillation counting	ki	0.0003	uM
ethyl 2-[[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]amino]-2-phenylacetate	1679136: Displacement of [3H]-HEMADO from human A3 receptor expressed in CHO cell membrane by radioligand binding assay	ki	0.0003	uM
(2S)-N-[9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-2-phenylpropanamide	34710: Binding affinity at cloned human adenosine A3 receptor expressed in HEK293 cells was determined using [125I]AB-MECA as radioligand	ki	0.0004	uM
1-[4-(furan-2-yl)-11-propyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-methylphenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0004	uM
1-[11-butyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-chlorophenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0004	uM
1-(4-bromophenyl)-3-[11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0004	uM
1-[4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-yl]-3-(4-nitrophenyl)urea	238660: Binding affinity for human adenosine A3 receptor	ki	0.0004	uM

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Adenosine	decreases activity, increases activity, increases expression, affects reaction, affects activity (+1 more)	4
Lipopolysaccharides	decreases expression, affects cotreatment, decreases reaction	2
bisphenol A	decreases methylation	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, decreases reaction	1
tamibarotene	affects expression	1
PD 81723	affects activity, affects binding, affects reaction	1
2-chloro-N(6)-(3-iodobenzyl)adenosine-5’-N-methyluronamide	affects binding, increases activity	1
9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline	affects binding, decreases activity	1
MRE 3008-F20	affects binding, decreases reaction	1
VUF 5455	affects activity, affects binding, affects reaction	1
4-allyl-8-ethyl-7,8-dihydro-2-(3-methoxy-1-methyl-1H-pyrazol-5-yl)-1H-imidazo(2,1-i)purin-5(4H)-one	affects binding, decreases reaction	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Amphotericin B	increases expression	1
Aspirin	affects response to substance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression	1
Calcitriol	decreases expression	1
Cisplatin	increases expression	1
Indomethacin	increases expression	1
Methotrexate	increases expression	1
Ozone	affects expression, increases abundance	1
Pyrazoles	affects binding, decreases activity	1
Quinolines	decreases activity, affects binding	1
Silver	decreases expression	1
Tretinoin	affects expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

1608 unique, capped per target: 1281 binding, 325 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014572	Binding	Selectivity ratio of Ki for human adenosine A1 receptor to Ki for human adenosine A3 receptor	Structure-activity relationship studies of a new series of imidazo[2,1-f]purinones as potent and selective A(3) adenosine receptor antagonists. — Bioorg Med Chem
CHEMBL3413626	Functional	Selectivity ratio of EC50 for human recombinant A3 adenosine receptor expressed in CHO cells to EC50 for human recombinant A1 adenosine receptor expressed in CHO cells by cAMP assay	In vivo phenotypic screening for treating chronic neuropathic pain: modification of C2-arylethynyl group of conformationally constrained A3 adenosine receptor agonists. — J Med Chem
CHEMBL5228307	Toxicity	Inhibition of A3 adenosine receptor (unknown origin)	Optimization of a Screening Hit toward M2912, an Oral Tankyrase Inhibitor with Antitumor Activity in Colorectal Cancer Models. — J Med Chem

Cellosaurus cell lines

6 cell lines: 4 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0S3	ACTOne ADORA3	Transformed cell line	Female
CVCL_H386	CHO-K1/ADORA3/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KS25	GeneBLAzer ADORA3-Galpha15-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KU75	cAMP Hunter CHO-K1 ADORA3 Gi	Spontaneously immortalized cell line	Female
CVCL_KW24	PathHunter CHO-K1 ADORA3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZJ94	Tango ADORA3-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.