ADK

Summary

ADK (adenosine kinase, HGNC:257) is a protein-coding gene on chromosome 10q22.2, encoding Adenosine kinase (P55263). Adenosine kinase that mediates the phosphorylation of the purine nucleoside adenosine at the 5’ position in an ATP-dependent manner: catalyzes phosphorylation of both unmodified and modified adenosines.

This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 132 — RefSeq curated summary.

At a glance

• Gene–disease (curated): adenosine kinase deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 191 total — 9 pathogenic, 7 likely-pathogenic
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006721

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:257
Approved symbol	ADK
Name	adenosine kinase
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	AK
Ensembl gene	ENSG00000156110
Ensembl biotype	protein_coding
OMIM	102750
Entrez	132

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000286621, ENST00000372734, ENST00000467840, ENST00000478611, ENST00000539909, ENST00000541550, ENST00000661461, ENST00000672394, ENST00000672429, ENST00000672604, ENST00000672920, ENST00000673027, ENST00000673310, ENST00000673352, ENST00000854555, ENST00000854556, ENST00000933492, ENST00000960305

RefSeq mRNA: 6 — MANE Select: NM_006721 NM_001123, NM_001202449, NM_001202450, NM_001369123, NM_001369124, NM_006721

CCDS: CCDS55716, CCDS55717, CCDS7343, CCDS7344, CCDS91270

Canonical transcript exons

ENST00000539909 — 11 exons

Exon	Start	End
ENSE00001024568	74394141	74394313
ENSE00001024570	74398471	74398579
ENSE00001178540	74314667	74314745
ENSE00001248825	74670183	74670269
ENSE00001248829	74600379	74600493
ENSE00001248835	74589282	74589317
ENSE00001310865	74525256	74525426
ENSE00002258874	74708321	74709290
ENSE00003553900	74200764	74200838
ENSE00003627238	74224538	74224591
ENSE00003891182	74151221	74151343

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.9968 / max 655.1308, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105584	36.3845	1819
105581	7.9428	1714
105583	5.1211	1413
105585	4.2097	1415
105582	0.3387	145

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.67	gold quality
tongue squamous epithelium	UBERON:0006919	96.06	gold quality
liver	UBERON:0002107	95.32	gold quality
right lobe of liver	UBERON:0001114	95.14	gold quality
calcaneal tendon	UBERON:0003701	95.00	gold quality
oral cavity	UBERON:0000167	93.95	gold quality
gingiva	UBERON:0001828	93.62	gold quality
esophagus mucosa	UBERON:0002469	93.54	gold quality
islet of Langerhans	UBERON:0000006	93.43	gold quality
ventricular zone	UBERON:0003053	93.25	gold quality
gingival epithelium	UBERON:0001949	93.09	gold quality
heart right ventricle	UBERON:0002080	92.60	gold quality
buccal mucosa cell	CL:0002336	91.98	gold quality
skin of leg	UBERON:0001511	91.47	gold quality
epithelium of esophagus	UBERON:0001976	91.46	gold quality
zone of skin	UBERON:0000014	91.42	gold quality
skin of abdomen	UBERON:0001416	91.40	gold quality
upper leg skin	UBERON:0004262	91.36	gold quality
pharyngeal mucosa	UBERON:0000355	91.35	gold quality
body of tongue	UBERON:0011876	91.21	gold quality
triceps brachii	UBERON:0001509	90.79	gold quality
squamous epithelium	UBERON:0006914	90.70	gold quality
cervix epithelium	UBERON:0004801	90.67	gold quality
esophagus squamous epithelium	UBERON:0006920	90.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.55	gold quality
ganglionic eminence	UBERON:0004023	90.51	gold quality
tendon	UBERON:0000043	90.27	gold quality
mammalian vulva	UBERON:0000997	90.16	gold quality
upper arm skin	UBERON:0004263	90.14	gold quality
skin of hip	UBERON:0001554	90.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, PITX2

miRNA regulators (miRDB)

61 targeting ADK, 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-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-561-3P	99.64	70.90	3647

Literature-anchored findings (GeneRIF, showing 17)

• Equilibrative nucleoside transporters (hENT1, hENT2) together with adenosine kinase and 5’-nucleotidase play a crucial role in the regulation of CFTR through an adenosine-dependent pathway in human airway epithelia. (PMID:12820662)
• role for HIF-1alpha in transcriptional repression of AK in hypoxia (PMID:18309031)
• adenosine kinase gene expression was significantly higher in cancer than in normal-appearing tissue, in line with our previous measurements of adenosine kinase enzyme activities in colorectal tumor samples (PMID:18600536)
• both deoxycytidine kinase and adenosine kinase are involved in this model of ADA deficiency (PMID:18600545)
• This study reports for the first time subcellular localization of the enzyme AdK in mammalian cells. (PMID:19635462)
• The catalytic properties, gene expression and protein levels of certain proteins involved in mitochondrial ATP synthesis, such as F1F0-ATPase, ANT and AK, in human skin fibroblasts with trisomic karyotype, compared them with euploid fibroblasts. (PMID:20698827)
• The results of this study suggested that dysregulation of ADK in astrocytes is a common pathologic hallmark of temporal lobe epilepsy. (PMID:21635241)
• Data show that we a significantly higher expression of ADK in the peritumoral infiltrated tissue of patients with epilepsy than in patients without epilepsy. (PMID:22092111)
• These results suggest that upregulation of ADK is a common pathologic hallmark of Rasmussen encephalitis and that ADK might be a target in the treatment of epilepsy associated with Rasmussen encephalitis. (PMID:24128682)
• The results of this study suggest that upregulation of ADK is a common pathologic component of FCDIIB. (PMID:25575137)
• rs11001109 rare allele homozygosity is associated with increased risk of post-traumatic epilepsy development after brain injury. (PMID:26040919)
• ADA and ADK are involved in glioma progression; increased ADA and ADK levels in peritumoral tissues may be associated with epilepsy in glioma patients. (PMID:26329539)
• The results of this study showed that over-expression of the major adenosine removing enzyme ADK in reactive astrocytes and subpopulation of remaining neurons in Rasmussen Encephalitis patients plays an important role in the epileptogensis of Rasmussen Encephalitis. (PMID:28789481)
• Adenosine kinase deficiency: Three new cases and diagnostic value of hypermethioninemia. (PMID:33309011)
• Genetic variations of adenosine kinase as predictable biomarkers of efficacy of vagus nerve stimulation in patients with pharmacoresistant epilepsy. (PMID:34479194)
• Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation. (PMID:36181835)
• Adenosine kinase inhibits beta-cell proliferation by upregulating DNA methyltransferase 3A expression. (PMID:38699782)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	adka	ENSDARG00000039429
danio_rerio	adkb	ENSDARG00000095947
mus_musculus	Adk	ENSMUSG00000039197
rattus_norvegicus	Adk	ENSRNOG00000012325
drosophila_melanogaster	Adk2	FBGN0036337
drosophila_melanogaster	Adk1	FBGN0037995
caenorhabditis_elegans		WBGENE00011128

Paralogs (3): KHK (ENSG00000138030), RBKS (ENSG00000171174), TMEM256 (ENSG00000205544)

Protein

Protein identifiers

Adenosine kinase — P55263 (reviewed: P55263)

Alternative names: Adenosine 5’-phosphotransferase, N6,N6-dimethyladenosine kinase, N6-isopentenyladenosine kinase, N6-methyladenosine kinase

All UniProt accessions (10): P55263, A0A140VJE0, A0A5F9ZGZ8, A0A5F9ZH31, A0A5F9ZH72, A0A5F9ZH76, A0A5F9ZH83, A0A5F9ZHJ1, A0A5K1VW54, A0A5K1VW94

UniProt curated annotations — full annotation on UniProt →

Function. Adenosine kinase that mediates the phosphorylation of the purine nucleoside adenosine at the 5’ position in an ATP-dependent manner: catalyzes phosphorylation of both unmodified and modified adenosines. Plays a key role in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification. Modified nucleosides are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs) and possess intrinsic cytotoxicity and must be cleared to prevent metabolic dysfunction. Catalyzes the phosphorylation of the free cytosolic methylated adenosine nucleotides N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A) into adenosine monophosphate (AMP) intermediates that are further detoxified by MAPDA/ADAL.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol Nucleus Cytoplasm.

Tissue specificity. Widely expressed. Highest level in placenta, liver, muscle and kidney.

Disease relevance. Hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:614300] A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activity is inhibited by 5-iodotubercidin and 5’-amino-5’-deoxyadenosine. Also inhibited by 5-(4-(Dimethylamino)phenyl)-6-(6-morpholin- 4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine, a alkynylpyrimidine class small-molecule.

Cofactor. Binds 3 Mg(2+) ions per subunit.

Pathway. Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenosine: step 1/1.

Similarity. Belongs to the carbohydrate kinase PfkB family.

Isoforms (4)

UniProt ID	Names	Canonical?
P55263-1	1, AK-L, Long	yes
P55263-2	2, AK-S, Short
P55263-3	3
P55263-4	4

RefSeq proteins (6): NP_001114, NP_001189378, NP_001189379, NP_001356052, NP_001356053, NP_006712* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001805	Adenokinase	Family
IPR002173	Carboh/pur_kinase_PfkB_CS	Conserved_site
IPR011611	PfkB_dom	Domain
IPR029056	Ribokinase-like	Homologous_superfamily

Pfam: PF00294

Enzyme classification (BRENDA):

• EC 2.7.1.20 — adenosine kinase (BRENDA: 40 organisms, 206 substrates, 498 inhibitors, 152 Km, 68 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADENOSINE	—	47
ATP	0.0014–1.282	25
3’-DEOXYADENOSINE	0.036–1.84	5
2’-DEOXYADENOSINE	0.077–0.66	3
RIBAVIRIN	0.54–7.8	3
2-METHYLADENOSINE	0.079–0.709	2
3’-AMINO-3’-DEOXYADENOSINE	0.26–0.61	2
6-METHYLMERCAPTOPURINE RIBOSIDE	0.0038–0.01	2
CTP	0.049–0.61	2
GTP	0.054–0.082	2
INOSINE	0.57–0.8	2
TUBERCIDIN	0.0833–0.4	2
UTP	0.056–0.34	2
VIRAMIDINE	7.7–16	2
2’-AMINO-2’,3’-DIDEOXYADENOSINE	0.34	1

Catalyzed reactions (Rhea), 4 shown:

• adenosine + ATP = AMP + ADP + H(+) (RHEA:20824)
• N(6)-methyladenosine + ATP = N(6)-methyl-AMP + ADP + H(+) (RHEA:86211)
• N(6),N(6)-dimethyladenosine + ATP = N(6),N(6)-dimethyl-AMP + ADP + H(+) (RHEA:86215)
• N(6)-(dimethylallyl)adenosine + ATP = N(6)-(dimethylallyl)adenosine 5’-phosphate + ADP + H(+) (RHEA:86219)

UniProt features (81 total): helix 17, strand 16, sequence variant 11, mutagenesis site 10, binding site 8, sequence conflict 8, splice variant 3, modified residue 2, turn 2, initiator methionine 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1BX4	X-RAY DIFFRACTION	1.5
2I6A	X-RAY DIFFRACTION	2.2
2I6B	X-RAY DIFFRACTION	2.3
9O7R	X-RAY DIFFRACTION	2.41
4O1L	X-RAY DIFFRACTION	2.5
9O7P	X-RAY DIFFRACTION	2.51
9O7Q	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55263-F1	93.40	0.87

Functional residue map

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

Catalytic / active sites (1): 317 (proton acceptor)

Ligand- & substrate-binding residues (8): 148; 317; 31; 35; 49; 81; 85; 147

Post-translational modifications (2): 2, 77

Mutagenesis-validated functional residues (10):

Position	Phenotype
11–12	abolishes nuclear localization.
33	abolished ability to mediate phosphorylation of unmodified and modified adenosines.
35	abolished ability to mediate phosphorylation of unmodified and modified adenosines.
57	abolished ability to mediate phosphorylation of unmodified and modified adenosines.
153	increased ability to phosphorylate n(6)-methyladenosine (m6a), n(6),n(6)-dimethyladenosine (m6,6a), n(6)-isopentenyladen
155	decreased ability to phosphorylate n(6),n(6)-dimethyladenosine (m6,6a) and n(6)-isopentenyladenosine (i6a), but not n(6)
187	abolished ability to mediate phosphorylation of unmodified and modified adenosines.
218	decreased ability to phosphorylate n(6)-methyladenosine (m6a) and n(6),n(6)-dimethyladenosine (m6,6a).
313	decreased ability to phosphorylate n(6),n(6)-dimethyladenosine (m6,6a) and n(6)-isopentenyladenosine (i6a).
317	abolished ability to mediate phosphorylation of unmodified and modified adenosines.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-74217	Purine salvage
R-HSA-9755088	Ribavirin ADME
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-8956321	Nucleotide salvage
R-HSA-9748784	Drug ADME

MSigDB gene sets: 388 (showing top): RNGTGGGC_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MODULE_56, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, STOSSI_RESPONSE_TO_ESTRADIOL, YY1_Q6, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (10): purine nucleobase metabolic process (GO:0006144), purine ribonucleoside salvage (GO:0006166), dATP biosynthetic process (GO:0006175), ribonucleoside monophosphate biosynthetic process (GO:0009156), GMP salvage (GO:0032263), AMP salvage (GO:0044209), dAMP salvage (GO:0106383), adenosine salvage (GO:0006169), phosphate-containing compound metabolic process (GO:0006796), small molecule metabolic process (GO:0044281)

GO Molecular Function (8): RNA binding (GO:0003723), adenosine kinase activity (GO:0004001), deoxyadenosine kinase activity (GO:0004136), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Nucleotide salvage	1
Drug ADME	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
purine ribonucleotide salvage	2
AMP biosynthetic process	2
dAMP biosynthetic process	2
metabolic process	2
nucleobase metabolic process	1
purine-containing compound metabolic process	1
purine-containing compound salvage	1
nucleoside salvage	1
purine ribonucleoside biosynthetic process	1
purine deoxyribonucleotide biosynthetic process	1
deoxyribonucleoside triphosphate biosynthetic process	1
purine deoxyribonucleoside triphosphate biosynthetic process	1
dATP metabolic process	1
nucleoside monophosphate biosynthetic process	1
GMP biosynthetic process	1
purine deoxyribonucleotide salvage	1
purine ribonucleoside salvage	1
adenosine biosynthetic process	1
nucleic acid binding	1
nucleoside kinase activity	1
deoxynucleoside kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADK	SPEF2	Q9C093	929
ADK	APRT	P07741	925
ADK	ADA	P00813	875
ADK	PURA	Q00577	818
ADK	GNPTAB	Q3T906	817
ADK	PNP	P00491	770
ADK	HPRT1	P00492	766
ADK	MDH2	P40926	747
ADK	SLC29A1	Q99808	733
ADK	AMPD3	Q01432	729
ADK	AMPD2	Q01433	728
ADK	AHCY	P23526	713
ADK	NT5E	P21589	707
ADK	AMPD1	P23109	694
ADK	ADSL	P30566	691

IntAct

30 interactions, top by confidence:

A	B	Type	Score
FICD	ADK	psi-mi:“MI:0915”(physical association)	0.370
SRD5A3	ADK	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
CDKN2A	NHERF1	psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
WIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
ETFBKMT	NR2F6	psi-mi:“MI:0914”(association)	0.350
ZNG1A	ADK	psi-mi:“MI:0914”(association)	0.350
MAVS	CHMP2A	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DNAJC30	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
CSDE1	VPS37C	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	QDPR	psi-mi:“MI:0914”(association)	0.350
SWSAP1	NACA	psi-mi:“MI:2364”(proximity)	0.270
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
btuB	ADK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), ADK (Co-fractionation), NNMT (Co-fractionation), NQO1 (Co-fractionation), PCBP1 (Co-fractionation), PITPNB (Co-fractionation), RBM12 (Co-fractionation), ADK (Affinity Capture-MS), ADK (Affinity Capture-MS)

ESM2 similar proteins: A2WXV8, A2YQL4, E9AD19, F1Q575, K7VCB9, O34768, O48881, O49923, O60116, O82616, O93919, P29266, P31937, P37829, P47143, P55262, P55263, P55264, P78825, Q00472, Q0J8G4, Q0JGZ6, Q0UVK8, Q2HJD7, Q2QWK9, Q42586, Q42896, Q42942, Q54MB5, Q5F4K8, Q5M731, Q5R5E7, Q64640, Q6K2E1, Q6NYF0, Q6XZ78, Q6XZ79, Q7XJ81, Q8LPS1, Q93WX6

Diamond homologs: D4GR05, E0J5J4, E9AD19, O29891, O49923, O93919, P37647, P47143, P55262, P55263, P55264, P78825, Q54MB5, Q64640, Q9LZG0, Q9SF85, Q9TVW2, D9TT10, P77493, Q54UQ4, Q5JEK6, D4GSE6, Q8RMD4, P45416, D4GYE6, A1A6H3, B8DCT6, C1KZA1, Q723S9, P45543, Q83JB1, Q8X839

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ADK	“down-regulates quantity”	adenosine	“chemical modification”
ADK	“down-regulates quantity”	ATP	“chemical modification”
ADK	“up-regulates quantity”	AMP	“chemical modification”
ADK	“up-regulates quantity”	ADP(3-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	7
Uncertain significance	74
Likely benign	63
Benign	20

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
2031084	NM_006721.4(ADK):c.328_331del (p.Asp110fs)	Pathogenic
2423733	NC_000010.10:g.(?75936631)(76468203_?)del	Pathogenic
2425795	NC_000010.10:g.(?76349020)(78317046_?)del	Pathogenic
29603	NM_006721.4(ADK):c.953C>A (p.Ala318Glu)	Pathogenic
29604	NM_006721.4(ADK):c.704A>C (p.Asp235Ala)	Pathogenic
29605	NM_006721.4(ADK):c.89G>A (p.Gly30Glu)	Pathogenic
3775248	NM_006721.4(ADK):c.647_651del (p.Ala216fs)	Pathogenic
395153	GRCh37/hg19 10q22.2-22.3(chr10:75542067-79428995)x1	Pathogenic
58745	GRCh38/hg38 10q22.1-22.2(chr10:72720628-75612374)x1	Pathogenic
2584480	NM_006721.4(ADK):c.642_645del (p.Ser215fs)	Likely pathogenic
2584481	NM_006721.4(ADK):c.916C>T (p.Gln306Ter)	Likely pathogenic
3244961	NC_000010.10:g.(?76360117)(76360271_?)dup	Likely pathogenic
3597273	NM_006721.4(ADK):c.-10_4del (p.Met1fs)	Likely pathogenic
3597287	NM_006721.4(ADK):c.569_570del (p.Thr190fs)	Likely pathogenic
4845594	NM_006721.4(ADK):c.64A>T (p.Arg22Ter)	Likely pathogenic
800875	NM_006721.4(ADK):c.813dup (p.Asn272fs)	Likely pathogenic

SpliceAI

5949 predictions. Top by Δscore:

Variant	Effect	Δscore
10:74151342:AGGTG:A	donor_loss	1.0000
10:74151344:G:T	donor_loss	1.0000
10:74200760:TTAGA:T	acceptor_loss	1.0000
10:74200761:TA:T	acceptor_loss	1.0000
10:74200762:A:AG	acceptor_gain	1.0000
10:74200762:AGAGA:A	acceptor_loss	1.0000
10:74200763:G:GT	acceptor_gain	1.0000
10:74200763:GA:G	acceptor_gain	1.0000
10:74200763:GAGA:G	acceptor_gain	1.0000
10:74200763:GAGAA:G	acceptor_gain	1.0000
10:74200834:GATAA:G	donor_gain	1.0000
10:74200835:A:G	donor_gain	1.0000
10:74200836:TAA:T	donor_gain	1.0000
10:74200839:G:GG	donor_gain	1.0000
10:74224587:GAACT:G	donor_gain	1.0000
10:74224592:G:GG	donor_gain	1.0000
10:74314661:TTATA:T	acceptor_loss	1.0000
10:74314662:TATAG:T	acceptor_loss	1.0000
10:74314664:TAGGT:T	acceptor_loss	1.0000
10:74314665:A:T	acceptor_loss	1.0000
10:74314666:G:T	acceptor_loss	1.0000
10:74394136:TACA:T	acceptor_loss	1.0000
10:74394137:ACAGT:A	acceptor_gain	1.0000
10:74394138:CAG:C	acceptor_loss	1.0000
10:74394139:A:AG	acceptor_gain	1.0000
10:74394139:A:AT	acceptor_loss	1.0000
10:74394139:AGT:A	acceptor_gain	1.0000
10:74394139:AGTG:A	acceptor_gain	1.0000
10:74394140:G:GA	acceptor_gain	1.0000
10:74394140:GT:G	acceptor_gain	1.0000

AlphaMissense

2411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:74394181:G:A	G105E	0.998
10:74394280:G:A	G138E	0.998
10:74525259:T:C	F187L	0.998
10:74525261:T:A	F187L	0.998
10:74525261:T:G	F187L	0.998
10:74670255:A:T	D317V	0.998
10:74200799:T:C	L34P	0.997
10:74394214:T:C	L116P	0.997
10:74394289:C:A	A141D	0.997
10:74525299:C:A	A200D	0.997
10:74525352:T:C	F218L	0.997
10:74525354:T:A	F218L	0.997
10:74525354:T:G	F218L	0.997
10:74670254:G:C	D317H	0.997
10:74670255:A:C	D317A	0.997
10:74670255:A:G	D317G	0.997
10:74670257:G:C	A318P	0.997
10:74708375:G:A	G340D	0.997
10:74200786:G:A	G30R	0.996
10:74200786:G:C	G30R	0.996
10:74200799:T:A	L34H	0.996
10:74200802:A:C	D35A	0.996
10:74394141:T:A	W92R	0.996
10:74394141:T:C	W92R	0.996
10:74398476:T:C	L151P	0.996
10:74398494:C:A	A157D	0.996
10:74670256:T:A	D317E	0.996
10:74670256:T:G	D317E	0.996
10:74670267:G:A	G321E	0.996
10:74200791:T:A	N31K	0.995

dbSNP variants (sampled 300 via entrez): RS1000006654 (10:74345143 G>A), RS1000011178 (10:74329767 A>G), RS1000011996 (10:74367741 C>A,T), RS1000018360 (10:74392238 T>C), RS1000021426 (10:74413340 T>C), RS1000021540 (10:74558319 T>A), RS1000022724 (10:74613474 A>G), RS1000027748 (10:74229890 G>T), RS1000028757 (10:74277408 T>C), RS1000038116 (10:74420238 G>A), RS1000038484 (10:74608452 C>A), RS1000056540 (10:74222828 A>G), RS1000056980 (10:74620376 T>C,G), RS1000057519 (10:74469036 T>C), RS1000066544 (10:74511972 T>C)

Disease associations

OMIM: gene MIM:102750 | disease phenotypes: MIM:611094, MIM:614300, MIM:606170

GenCC curated gene-disease

Disease	Classification	Inheritance
adenosine kinase deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
adenosine kinase deficiency	Definitive	AR

Mondo (2): adenosine kinase deficiency (MONDO:0100255), genitopatellar syndrome (MONDO:0011640)

Orphanet (3): Hypermethioninemia encephalopathy due to adenosine kinase deficiency (Orphanet:289290), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Genitopatellar syndrome (Orphanet:85201)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C565255	Genitopatellar Syndrome (supp.)
C567015	Mental Retardation, Autosomal Recessive 8 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3589 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 48,111 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL2408045	SAPITINIB	2	1,460
CHEMBL513909	BI-2536	2	895
CHEMBL1908394	GSK-461364	1	1,093

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10824095	ADK		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
A134974	Inhibition	10.2	pIC50
ABT702	Inhibition	8.8	pIC50

ChEMBL bioactivities

584 potent at pChembl≥5 of 621 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	IC50	0.06	nM	CHEMBL4460859
10.00	IC50	0.1	nM	CHEMBL330432
9.70	IC50	0.2	nM	CHEMBL99707
9.70	IC50	0.2	nM	CHEMBL370164
9.52	IC50	0.3	nM	CHEMBL194294
9.40	IC50	0.4	nM	CHEMBL226486
9.33	IC50	0.47	nM	CHEMBL343247
9.30	IC50	0.5	nM	CHEMBL100421
9.30	IC50	0.5	nM	CHEMBL370011
9.30	IC50	0.5	nM	CHEMBL426472
9.22	IC50	0.6	nM	CHEMBL322611
9.22	IC50	0.6	nM	CHEMBL200169
9.10	IC50	0.8	nM	CHEMBL319315
9.10	IC50	0.8	nM	CHEMBL436598
9.10	IC50	0.8	nM	CHEMBL200630
9.05	IC50	0.9	nM	CHEMBL198566
9.05	IC50	0.9	nM	5-IODO,5’-DEOXYTUBERCIDIN
9.00	IC50	1	nM	CHEMBL328826
9.00	IC50	1	nM	CHEMBL370218
9.00	IC50	1	nM	CHEMBL438449
9.00	IC50	1	nM	CHEMBL449402
9.00	IC50	1	nM	CHEMBL225729
9.00	IC50	1	nM	CHEMBL225672
9.00	IC50	1	nM	CHEMBL98551
9.00	IC50	1	nM	CHEMBL317603
9.00	IC50	1	nM	CHEMBL174158
8.92	IC50	1.2	nM	CHEMBL318918
8.89	IC50	1.3	nM	CHEMBL372796
8.89	IC50	1.3	nM	CHEMBL370654
8.89	IC50	1.3	nM	CHEMBL66089
8.89	IC50	1.3	nM	CHEMBL62576
8.85	IC50	1.4	nM	CHEMBL65665
8.82	IC50	1.5	nM	CHEMBL360273
8.82	IC50	1.5	nM	CHEMBL66277
8.82	IC50	1.5	nM	CHEMBL318929
8.82	IC50	1.5	nM	CHEMBL98867
8.82	IC50	1.5	nM	CHEMBL344529
8.77	IC50	1.7	nM	CHEMBL66089
8.74	IC50	1.8	nM	CHEMBL62974
8.70	IC50	2	nM	CHEMBL66089
8.70	IC50	2	nM	CHEMBL371704
8.70	IC50	2	nM	CHEMBL435120
8.70	IC50	2	nM	CHEMBL200575
8.70	IC50	2	nM	CHEMBL197112
8.70	IC50	2	nM	CHEMBL216697
8.64	IC50	2.3	nM	CHEMBL317818
8.60	IC50	2.5	nM	CHEMBL338508
8.57	IC50	2.7	nM	CHEMBL432062
8.55	IC50	2.8	nM	CHEMBL141327
8.55	IC50	2.8	nM	CHEMBL101805

PubChem BioAssay actives

564 with measured affinity, of 1379 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
(2R,3S,4R,5R)-2-(aminomethyl)-5-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol	33985: Inhibition of recombinant human adenosine kinase	ic50	0.0001	uM
(1S,2R,3S,5R)-3-amino-5-(4-amino-3-iodopyrazolo[3,4-d]pyrimidin-1-yl)cyclopentane-1,2-diol	1628630: Inhibition of human adenosine kinase assessed as reduction in conversion of adenosine to AMP	ic50	0.0001	uM
(2R,3R,4S,5R)-2-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-5-(aminomethyl)oxolane-3,4-diol	33985: Inhibition of recombinant human adenosine kinase	ic50	0.0002	uM
N-(4-chlorophenyl)-2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]acetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0002	uM
(5R,6R,7S)-5-[4-(4-fluoroanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]-4-oxaspiro[2.4]heptane-6,7-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0003	uM
5-(1-benzothiophen-2-yl)-6-[2-(6-morpholin-4-yl-3-pyridinyl)ethynyl]pyrimidin-4-amine	287435: Inhibition of cytosolic adenosine kinase	ic50	0.0004	uM
(2R,3R,4S,5S)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0005	uM
2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]-N-phenylacetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0005	uM
N-cyclopropyl-2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]ethanethioamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0005	uM
(2R,3R,4S,5R)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol	1628630: Inhibition of human adenosine kinase assessed as reduction in conversion of adenosine to AMP	ic50	0.0005	uM
(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-(aminomethyl)oxolane-3,4-diol	33985: Inhibition of recombinant human adenosine kinase	ic50	0.0006	uM
2-[[7-[(2R,3R,4R)-3,4-dihydroxyoxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]-N-phenylacetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0006	uM
(2R,3R,4S,5R)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0008	uM
2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]-N-methylacetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0008	uM
(2R,3R,4S,5S)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0008	uM
2-[[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-phenylpyrazolo[3,4-d]pyrimidin-4-yl]amino]-N-phenylacetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0009	uM
(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol	271974: Inhibition of human cytosolic AK	ic50	0.0009	uM
(2R,3R,4S,5R)-2-(4-anilino-6-bromo-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol	240636: Inhibitory activity against Human Recombinant Adenosine Kinase	ic50	0.0010	uM
(2R,3R,4S,5R)-2-[4-(4-hydroxyanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]-5-methyloxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0010	uM
(2R,3R,4R)-2-[4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-5-(2-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0010	uM
7-[(4aS,7aS)-6-benzyl-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b]pyridin-1-yl]-2-phenyl-[1,3]oxazolo[5,4-d]pyrimidine	33988: Inhibitory activity against human adenosine kinase expressed in Escherichia coli	ic50	0.0010	uM
N-cyclopentyl-2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]acetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0010	uM
5-(4-chlorophenyl)-6-[2-[6-[2-methoxyethyl(methyl)amino]-3-pyridinyl]ethynyl]pyrimidin-4-amine	287435: Inhibition of cytosolic adenosine kinase	ic50	0.0010	uM
1-[4-[5-[2-[6-amino-5-(4-chlorophenyl)pyrimidin-4-yl]ethynyl]-2-pyridinyl]piperazin-1-yl]ethanone	287435: Inhibition of cytosolic adenosine kinase	ic50	0.0010	uM
5-(1-benzofuran-2-yl)-6-[2-(6-morpholin-4-yl-3-pyridinyl)ethynyl]pyrimidin-4-amine	287435: Inhibition of cytosolic adenosine kinase	ic50	0.0010	uM
4-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-(4-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzonitrile	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0010	uM
(2R,3R,4S,5R)-2-[4-anilino-5-(4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-5-methyloxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0012	uM
N-cyclopropyl-N’-[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]oxamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0013	uM
5-(3-bromophenyl)-7-(6-morpholin-4-yl-3-pyridinyl)pyrido[2,3-d]pyrimidin-4-amine	33512: In vitro concentration required for 50% inhibition against Adenosine Kinase (AK) in the presence of enzyme	ic50	0.0013	uM
5-(3-bromophenyl)-7-(6-thiomorpholin-4-yl-3-pyridinyl)pyrido[2,3-d]pyrimidin-4-amine	33512: In vitro concentration required for 50% inhibition against Adenosine Kinase (AK) in the presence of enzyme	ic50	0.0013	uM
N-cyclobutyl-2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]acetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0013	uM
5-(3-bromophenyl)-7-[6-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-3-pyridinyl]pyrido[2,3-d]pyrimidin-4-amine	33512: In vitro concentration required for 50% inhibition against Adenosine Kinase (AK) in the presence of enzyme	ic50	0.0014	uM
(2R,3S,4R,5R)-2-methyl-5-[4-(4-methylanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0015	uM
(2R,3R,4S,5R)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-(azidomethyl)oxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0015	uM
(2R,3R,4S,5S)-2-[4-(4-fluoroanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]-5-(hydroxymethyl)oxolane-3,4-diol	33984: Inhibitory activity against human recombinant adenosine kinase	ic50	0.0015	uM
7-[(3aS,6aS)-1-benzyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrol-5-yl]-2-phenyl-[1,3]oxazolo[5,4-d]pyrimidine	33988: Inhibitory activity against human adenosine kinase expressed in Escherichia coli	ic50	0.0015	uM
(2R,3R,4S,5R)-2-[4-(4-fluoroanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]-5-methyloxolane-3,4-diol	1628630: Inhibition of human adenosine kinase assessed as reduction in conversion of adenosine to AMP	ic50	0.0015	uM
1-[5-[4-amino-5-(3-bromophenyl)pyrido[2,3-d]pyrimidin-7-yl]-2-pyridinyl]piperidin-4-ol	33512: In vitro concentration required for 50% inhibition against Adenosine Kinase (AK) in the presence of enzyme	ic50	0.0018	uM
2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]-N-(3-methoxypropyl)acetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0020	uM
4-[[7-[(2R,3R,4R)-3,4-dihydroxyoxolan-2-yl]-5-(4-ethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzonitrile	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0020	uM
(2R,3R,4R)-2-[4-(3-ethoxyanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0020	uM
5-[4-(dimethylamino)phenyl]-6-[2-(6-morpholin-4-yl-3-pyridinyl)ethynyl]pyrimidin-4-amine	287435: Inhibition of cytosolic adenosine kinase	ic50	0.0020	uM
2-[[7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-phenylpyrrolo[2,3-d]pyrimidin-4-yl]amino]acetamide	256903: Inhibitory activity against recombinant human adenosine kinase	ic50	0.0020	uM
(2R,3R,4S,5R)-2-[4-(4-chloroanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]-5-methyloxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0023	uM
6-[2-(6-morpholin-4-yl-3-pyridinyl)ethynyl]-5-(3-phenylpropyl)pyrimidin-4-amine	271974: Inhibition of human cytosolic AK	ic50	0.0025	uM
(2R,3R,4S,5R)-2-[4-(4-chloroanilino)-5-(4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-5-methyloxolane-3,4-diol	33987: Inhibition of recombinant human adenosine kinase	ic50	0.0027	uM
(2R,3R,4S,5S)-2-(4-anilino-3-phenylpyrazolo[3,4-d]pyrimidin-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol	33984: Inhibitory activity against human recombinant adenosine kinase	ic50	0.0028	uM
5-(3-bromophenyl)-7-[6-[4-(oxan-4-yloxymethyl)piperidin-1-yl]pyridazin-3-yl]pyrido[2,3-d]pyrimidin-4-amine	34002: Inhibitory concentration against adenosine kinase was determined	ic50	0.0028	uM
(2R,3R,4S,5R)-2-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol	33985: Inhibition of recombinant human adenosine kinase	ic50	0.0030	uM
(2R,3R,4R)-2-[4-(4-ethoxyanilino)-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	255140: Inhibitory concentration against human recombinant adenosine kinase using [14C]AMP as radioligand	ic50	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Benzo(a)pyrene	decreases expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation, increases expression	3
Aflatoxin B1	increases methylation, affects expression, decreases expression	3
trichostatin A	affects expression, decreases reaction, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	affects cotreatment, increases expression, decreases expression	2
Vorinostat	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	decreases expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium bichromate	decreases expression	1
enilconazole	increases expression	1
aflatoxin B2	increases methylation	1
lead chloride	affects cotreatment, increases expression	1
cadmium sulfate	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

169 unique, capped per target: 106 binding, 57 admet, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037326	Binding	Inhibition of adenosine kinase AMP binding site	Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5’-adenosinemonophosphate (AMP) mimics. — J Med Chem
CHEMBL4009402	ADMET	Drug metabolism in human BJ cells assessed as ADK-mediated 4-(Methylsulfanyl)-8-(beta-D-ribofuranosyl)-8H-thieno[2, 3:4,5]-pyrrolo[2,3-d]pyrimidine-5-O-monophosphate Sodium Salt formation per 5 x10'5 cells at 1 umol/L after 1 hr by UPLC-MS/	Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides. — J Med Chem
CHEMBL5723188	Functional	Affinity Biochemical interaction: (radiochemical assay, inhibition of AK activity in cell supernatants) EUB0002485aCl ADK	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1J5	Abcam HeLa ADK KO	Cancer cell line	Female
CVCL_B8AY	Abcam HCT 116 ADK KO	Cancer cell line	Male
CVCL_B9D0	Abcam A-549 ADK KO	Cancer cell line	Male
CVCL_D2DR	Abcam MCF-7 ADK KO	Cancer cell line	Female
CVCL_SB73	HAP1 ADK (-) 1	Cancer cell line	Male
CVCL_SB74	HAP1 ADK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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