DCK

Summary

DCK (deoxycytidine kinase, HGNC:2704) is a protein-coding gene on chromosome 4q13.3, encoding Deoxycytidine kinase (P27707). Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine.

Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased deoxycytidine kinase activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity.

Source: NCBI Gene 1633 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2704
Approved symbol	DCK
Name	deoxycytidine kinase
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000156136
Ensembl biotype	protein_coding
OMIM	125450
Entrez	1633

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000286648, ENST00000503359, ENST00000504730, ENST00000504952, ENST00000509617, ENST00000509764, ENST00000890385, ENST00000961150

RefSeq mRNA: 1 — MANE Select: NM_000788 NM_000788

CCDS: CCDS3548

Canonical transcript exons

ENST00000286648 — 7 exons

Exon	Start	End
ENSE00002041408	70993649	70993926
ENSE00003459650	71029352	71030914
ENSE00003526988	71025816	71025931
ENSE00003546252	71023559	71023706
ENSE00003553462	71026665	71026755
ENSE00003566405	71022367	71022560
ENSE00003636122	70998067	70998182

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1189 / max 553.5584, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48017	18.3954	1795
48018	3.7250	1051
48021	1.9985	1062

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	96.39	gold quality
buccal mucosa cell	CL:0002336	93.98	gold quality
monocyte	CL:0000576	93.78	gold quality
mononuclear cell	CL:0000842	93.69	gold quality
leukocyte	CL:0000738	93.63	gold quality
vermiform appendix	UBERON:0001154	93.58	gold quality
lymph node	UBERON:0000029	93.29	gold quality
cortical plate	UBERON:0005343	93.11	gold quality
secondary oocyte	CL:0000655	92.67	gold quality
ventricular zone	UBERON:0003053	92.52	gold quality
bone marrow	UBERON:0002371	92.38	gold quality
superficial temporal artery	UBERON:0001614	92.16	gold quality
ganglionic eminence	UBERON:0004023	91.96	gold quality
calcaneal tendon	UBERON:0003701	91.25	gold quality
caecum	UBERON:0001153	90.24	gold quality
endothelial cell	CL:0000115	89.75	gold quality
rectum	UBERON:0001052	89.55	gold quality
islet of Langerhans	UBERON:0000006	89.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.74	gold quality
epithelium of nasopharynx	UBERON:0001951	88.70	gold quality
oocyte	CL:0000023	88.67	gold quality
bone marrow cell	CL:0002092	88.63	gold quality
granulocyte	CL:0000094	88.59	gold quality
oral cavity	UBERON:0000167	88.58	gold quality
thymus	UBERON:0002370	88.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.08	gold quality
blood	UBERON:0000178	87.81	gold quality
spinal cord	UBERON:0002240	87.59	gold quality
spleen	UBERON:0002106	87.50	gold quality
nucleus accumbens	UBERON:0001882	87.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	39.73
E-ANND-3	yes	5.67
E-CURD-122	yes	5.01
E-MTAB-6386	no	353.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, PAX3, SP1, SP3, USF1, USF2

miRNA regulators (miRDB)

108 targeting DCK, 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-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• gene for thioredoxin peroxidase (DmTPx-1) was cloned and expressed, and the protein characterized (PMID:11877442)
• Activation of JNK/FOXO signaling in neurons increased the Jafrac1 expression level under both normal and oxidative stressed conditions. (PMID:19720829)
• Jafrac1-mediated reduction of hydrogen peroxide is required to maintain DE-cadherin protein levels in the early embryo. (PMID:21316590)
• alternatively spliced dCK forms found in acute myeloid leukemia cells play an important role in cytarabine resistance (PMID:11830489)
• Molecular basis of 2’,3’-dideoxycytidine-induced drug resistance in human cells. (PMID:11952160)
• Data show that inorganic tripolyphosphate (PPP(i)) is a good donor for human ceoxycytidine kinase and deoxyguanosine kinase. (PMID:12535661)
• human deoxycytidine kinase promoter activity is regulated by USF and Sp1 (PMID:14514691)
• dCK can act as a phosphorylase, similar to the nucleoside phosphorylase family of enzymes (PMID:15561147)
• analysis of antitumor drug binding to deoxycytidine kinase (PMID:15571255)
• dCK expression varies between individual samples and between different types of malignancies and may play a role in resistance to ara-C in particular tumor types (PMID:15571257)
• deoxycytidine kinase activity is stimulated by 2-chlorodeoxyadenosine and aphidicolin in the cellular context (PMID:15571258)
• deoxycytidine kinase activity is regulated by reversible phosphorylation (PMID:15571259)
• an increased expression of mRNA, specific for thymidine kinase 1, dCK and thymidine phosphorylase, may be involved in carcinogenic processes in the human thyroid (PMID:15978330)
• dCK activity can be controlled by phosphorylation in intact cells, and Ser-74 is required for activity (PMID:16361699)
• Crystal structures of a deoxycytidine kinase variant lacking a flexible insert (residues 65-79) reveal major changes in the donor base binding loop (residues 240-247) between UDP-bound and ADP-bound forms, involving significant main-chain rearrangement. (PMID:16401075)
• an increase in activity of dCK, TK1 and 2 might be involved in an adaptive response of cultured human squamous lung carcinoma cells to radiation by facilitation of DNA repair (PMID:16969512)
• deoxycytidine kinase has a role in lymphoma cell sensitivity to cladribine (PMID:17065053)
• analysis of phosphorylation sites on human deoxycytidine kinase (PMID:17065079)
• analysis of deoxycytidine kinase reversible phosphorylation in normal human lymphocytes (PMID:17065080)
• deoxycytidine kinase activity is enhanced after pulsed low dose rate and single dose gamma irradiation (PMID:17065085)
• deoxycytidine kinase, deoxyguanosine kinase, and cytosolic 5’-nucleotidase I are regulated in a cell cycle-dependent manner in MOLT-4 cells (PMID:17065091)
• study identified novel coding, promoter, intronic, and 3’-UTR genetic variants at the DCK locus in two major ethnic groups; results suggest that genetic variation in DCK influences its activity and expression (PMID:17855478)
• Phosphorylation may represent a mechanism to enhance the catalytic activity of the relatively slow dCK enzyme. (PMID:18258203)
• illuminate the key contributions of these two amino acid positions to enzyme function by demonstrating their ability to moderate substrate specificity (PMID:18361501)
• dCK and dGK were downregulated by approximately 70% in CEM cells and tested against six nucleoside (PMID:18600530)
• both deoxycytidine kinase and adenosine kinase are involved in this model of ADA deficiency (PMID:18600545)
• In leukoblasts from 82 patients with acute myeloid leukemia, various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes was observed. (PMID:18775979)
• 29 variations including 20 novel ones were identified in DCK from 256 Japanese cancer patients administered gemcitabine. (PMID:18974616)
• Several hydrophobic residues at position 104 endow dCK with thymidine kinase activity. (PMID:19159229)
• dCK can regulate the in vitro cellular response to Ara-C in acute myeloid leukemia cells (PMID:19287976)
• The DCK/cN-II ratio was again proportional to ara-CTP production and to ara-C sensitivity. (PMID:19428333)
• thymidylate synthase/ribonucleotide reductase gene silencing and deoxycytidine kinase::uridine monophosphate kinase fusion gene gene overexpression markedly improved gemcitabine’s therapeutic activity (PMID:19568409)
• Sensitivity of two pancreatic cancer cell lines transduced with deoxycytidine kinase to gemcitabine elevated dramatically in comparison with control cells. (PMID:20043109)
• dCK expression level in fludarabine-sensitive patients was much higher than in Flud-resistant patients. (PMID:20137114)
• Data show that phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify dCK activity, but phosphorylation of Thr-3 could promote dCK stability. (PMID:20544527)
• Data show that methylation was detected in one of the SP1 binding sites of the dCK promoter, in most tested cancer cell lines and in patient samples from brain tumors and leukemia. Methylation might therefore regulate transcription of dCK. (PMID:20544528)
• it is residue Asp133 of dCK that is most responsible for discriminating against the thymine base (PMID:20614893)
• Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in dCK activation by casein kinase 1 delta, strengthening the key role of this residue in the control of dCK activity. (PMID:20637175)
• Data show that dCK-360G allele was found to increase the risk of mucositis after exposure to low-dose cytarabine in childhood ALL therapy. (PMID:20890066)
• Data indicate that variant C28624T showed a lower risk of lymphopenia (P=0.04), but a higher risk of neutropenia. (PMID:21030078)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dck	ENSDARG00000044807
mus_musculus	Dck	ENSMUSG00000029366
rattus_norvegicus	Dck	ENSRNOG00000003296

Paralogs (3): DGUOK (ENSG00000114956), NDUFA10 (ENSG00000130414), TK2 (ENSG00000166548)

Protein

Protein identifiers

Deoxycytidine kinase — P27707 (reviewed: P27707)

Alternative names: Deoxyadenosine kinase, Deoxyguanosine kinase

All UniProt accessions (6): P27707, D6R9C6, D6RCP9, D6RFG8, D6RG38, F5CTF3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine. Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.

Subunit / interactions. Homodimer.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated and activated in vitro upon phosphorylation at Ser-74 by CSNK1D/CK1.

Similarity. Belongs to the DCK/DGK family.

RefSeq proteins (1): NP_000779* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002624	DCK/DGK	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031314	DNK_dom	Domain
IPR050566	Deoxyribonucleoside_kinase	Family

Pfam: PF01712

Enzyme classification (BRENDA):

• EC 2.7.1.74 — deoxycytidine kinase (BRENDA: 11 organisms, 283 substrates, 256 inhibitors, 244 Km, 179 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
2’-DEOXYADENOSINE	0.0085–1.437	27
2’-DEOXYGUANOSINE	0.021–2.266	23
DEOXYCYTIDINE	0.0001–0.071	22
2’-DEOXYCYTIDINE	0.0001–0.0089	16
ATP	0.001–0.2	15
UTP	0.0005–0.0578	13
THYMIDINE	0.0039–3.485	12
2-CHLORO-2’-DEOXYADENOSINE	0.001–0.024	8
1-BETA-D-ARABINOFURANOSYLCYTOSINE	0.003–0.024	6
DEOXYADENOSINE	0.093–0.89	6
DEOXYGUANOSINE	0.122–3	5
(-)-BETA-2’,3’-DIDEOXY-3’-THIACYTIDINE	0.003–0.015	4
2’,3’-DIDEOXYCYTIDINE	0.15–0.67	4
9-BETA-D-ARABINOFURANOSYLGUANINE	2–5	4
CLADRIBINE	0.0006–0.0155	4

Catalyzed reactions (Rhea), 3 shown:

• 2’-deoxyguanosine + ATP = dGMP + ADP + H(+) (RHEA:19201)
• 2’-deoxycytidine + a ribonucleoside 5’-triphosphate = dCMP + a ribonucleoside 5’-diphosphate + H(+) (RHEA:20061)
• 2’-deoxyadenosine + ATP = dAMP + ADP + H(+) (RHEA:23452)

UniProt features (45 total): helix 16, binding site 9, strand 7, mutagenesis site 5, modified residue 4, chain 1, active site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

58 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1P5Z	X-RAY DIFFRACTION	1.6
2NO7	X-RAY DIFFRACTION	1.7
7ZIA	X-RAY DIFFRACTION	1.7
2ZI5	X-RAY DIFFRACTION	1.77
2ZI6	X-RAY DIFFRACTION	1.77
2NO0	X-RAY DIFFRACTION	1.8
2NOA	X-RAY DIFFRACTION	1.8
2ZIA	X-RAY DIFFRACTION	1.8
7ZI7	X-RAY DIFFRACTION	1.8
7ZI9	X-RAY DIFFRACTION	1.8
4Q1E	X-RAY DIFFRACTION	1.85
7ZI1	X-RAY DIFFRACTION	1.85
4JLK	X-RAY DIFFRACTION	1.89
3QEO	X-RAY DIFFRACTION	1.9
1P62	X-RAY DIFFRACTION	1.9
2NO6	X-RAY DIFFRACTION	1.9
4Q1A	X-RAY DIFFRACTION	1.9
7ZI3	X-RAY DIFFRACTION	1.9
2NO1	X-RAY DIFFRACTION	1.91
4L5B	X-RAY DIFFRACTION	1.94
7ZIB	X-RAY DIFFRACTION	1.95
1P60	X-RAY DIFFRACTION	1.96
3KFX	X-RAY DIFFRACTION	1.96
2ZI7	X-RAY DIFFRACTION	1.97
7ZI8	X-RAY DIFFRACTION	1.99
3QEN	X-RAY DIFFRACTION	2
3IPX	X-RAY DIFFRACTION	2
4JLJ	X-RAY DIFFRACTION	2
4Q18	X-RAY DIFFRACTION	2
4Q1C	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27707-F1	89.13	0.74

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): 127 (proton acceptor)

Ligand- & substrate-binding residues (9): 240–242; 28–36; 53; 86; 97; 128; 133; 188–192; 197

Post-translational modifications (4): 11, 15, 72, 74

Mutagenesis-validated functional residues (5):

Position	Phenotype
74	4.5-fold increase in km.
100	strongly increased catalytic efficiency towards deoxycytidine; when associated with m-104 and a-133.
104	strongly increased catalytic efficiency towards deoxythymidine; when associated with a-133.
104	strongly increased catalytic efficiency towards deoxycytidine; when associated with v-100 and a-133.
133	strongly increased catalytic efficiency towards deoxycytidine; when associated with v-100 and m-104. strongly increased

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73614	Pyrimidine salvage
R-HSA-74217	Purine salvage

MSigDB gene sets: 309 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, E2F_Q4, E2F_Q4_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, E2F4DP1_01, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KONG_E2F3_TARGETS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, PATIL_LIVER_CANCER

GO Biological Process (7): pyrimidine nucleotide metabolic process (GO:0006220), dAMP salvage (GO:0106383), nucleoside phosphate biosynthetic process (GO:1901293), nucleobase-containing compound metabolic process (GO:0006139), deoxyribonucleoside monophosphate biosynthetic process (GO:0009157), CMP biosynthetic process (GO:0009224), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (11): deoxyadenosine kinase activity (GO:0004136), deoxycytidine kinase activity (GO:0004137), deoxyguanosine kinase activity (GO:0004138), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), cytidine kinase activity (GO:0043771), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), deoxynucleoside kinase activity (GO:0019136)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide salvage	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deoxynucleoside kinase activity	3
cellular anatomical structure	3
dAMP biosynthetic process	2
cytoplasm	2
intracellular membrane-bounded organelle	2
nucleotide metabolic process	1
pyrimidine-containing compound metabolic process	1
purine deoxyribonucleotide salvage	1
nucleoside phosphate metabolic process	1
nucleobase-containing compound biosynthetic process	1
organophosphate biosynthetic process	1
primary metabolic process	1
nucleoside monophosphate biosynthetic process	1
pyrimidine ribonucleoside monophosphate biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
CMP metabolic process	1
metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
CMP biosynthetic process	1
nucleoside kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
deoxyribonucleoside monophosphate biosynthetic process	1
nucleobase-containing compound kinase activity	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCK	CDA	P32320	941
DCK	TK1	P04183	887
DCK	SLC29A1	Q99808	875
DCK	DCTD	P32321	784
DCK	PDIA4	P13667	769
DCK	RRM1	P23921	753
DCK	SLC28A3	Q9HAS3	700
DCK	CMPK1	P30085	699
DCK	NT5C2	P49902	688
DCK	RRM2	P31350	676
DCK	SLC28A1	O00337	668
DCK	TYMS	P04818	660
DCK	P4HA2	O15460	650
DCK	SLC29A2	Q14542	633
DCK	UCK1	Q9HA47	610

IntAct

32 interactions, top by confidence:

A	B	Type	Score
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
DCK	DGUOK	psi-mi:“MI:0914”(association)	0.620
DGUOK	DCK	psi-mi:“MI:0915”(physical association)	0.620
DCK	TFEC	psi-mi:“MI:0915”(physical association)	0.370
DCK	DCK	psi-mi:“MI:0915”(physical association)	0.370
RXRG	DCK	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
DGUOK	DNM1L	psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350
ANKRD13A	DCK	psi-mi:“MI:0914”(association)	0.350
ISX	DCK	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
GZMH	DENND11	psi-mi:“MI:0914”(association)	0.350
ISX	GAPDHS	psi-mi:“MI:0914”(association)	0.350
P2RY8	BTAF1	psi-mi:“MI:0914”(association)	0.350
PLEKHG2	DCK	psi-mi:“MI:0914”(association)	0.350
ANKRD13A	HLA-DPB1	psi-mi:“MI:0914”(association)	0.350
DCK	KLK3	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CHTOP	C1orf226	psi-mi:“MI:0914”(association)	0.350
GPR17	C1QTNF9B	psi-mi:“MI:0914”(association)	0.350
ITM2B	DCK	psi-mi:“MI:0914”(association)	0.350
TMEM95	NEMP1	psi-mi:“MI:0914”(association)	0.350
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270
MED19	DCK	psi-mi:“MI:0915”(physical association)	0.000
DDX19B	DCK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (71): DCK (Affinity Capture-MS), DCK (Affinity Capture-MS), DCK (Affinity Capture-MS), PRKDC (Negative Genetic), DCK (Negative Genetic), JAK3 (Positive Genetic), MAP2K2 (Positive Genetic), DCK (Affinity Capture-MS), DCK (Affinity Capture-MS), DCK (Affinity Capture-MS), DCK (Synthetic Lethality), DCK (Two-hybrid), DCK (Two-hybrid), DCK (Two-hybrid), DACH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A173GP47, A0A1L8HV70, A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00338, O43704, O46503, O75897, P0CC03, P15709, P17988, P19217, P22789, P27707, P46560, P48769, P49887, P49888, P49891, P50234, P50235, P50236, P50237, P52840, P52841, P52843, P52844, P52847, Q06520, Q3T0Y3, Q3UZZ6, Q5ZJM7, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17, Q6WG18, Q7T2V2

Diamond homologs: A0A1L8HV70, O00142, P21974, P27707, P43346, P48769, Q16854, Q3MHR2, Q5ZJM7, Q5ZMF3, Q6DD33, Q6GPW6, Q9J579, Q9N0C5, Q9QX60, Q9R088, Q9XZT6, Q8FKZ1, P28855, Q6GZP0, Q197D1, Q54YL2, Q54UT2

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
ATM	“up-regulates activity”	DCK	phosphorylation
ATR	“up-regulates activity”	DCK	phosphorylation
CSNK1D	“up-regulates activity”	DCK	phosphorylation
DCK	“down-regulates quantity”	2’-deoxyadenosine	“chemical modification”
DCK	“down-regulates quantity”	ATP(4-)	“chemical modification”
DCK	“up-regulates quantity”	ADP(3-)	“chemical modification”
DCK	“down-regulates quantity”	2’-deoxyguanosine	“chemical modification”
DCK	“down-regulates quantity”	cytidine	“chemical modification”
DCK	“down-regulates quantity”	“cytidine 5’-monophosphate(2-)”	“chemical modification”
DCK	“down-regulates quantity”	2’-deoxycytidine	“chemical modification”
DCK	“up-regulates quantity”	“2’-deoxycytosine 5’-monophosphate(2-)”	“chemical modification”
PP2Ca_R1A_Bd	“down-regulates activity”	DCK	dephosphorylation
PPP2CA	“down-regulates activity”	DCK	dephosphorylation
PP2CA_R1A_R2A	“down-regulates activity”	DCK	dephosphorylation
DCK	“down-regulates activity”	CDK1	binding
DCK	up-regulates	G2/M_transition-checkpoint	phosphorylation
DCK	“up-regulates quantity”	“2’-deoxyadenosine 5’-monophosphate(2-)”	“chemical modification”
DCK	“up-regulates quantity”	“2’-deoxyguanosine 5’-monophosphate(2-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70998061:C:G	acceptor_gain	1.0000
4:70998062:A:AG	acceptor_gain	1.0000
4:70998065:A:AG	acceptor_gain	1.0000
4:70998065:A:C	acceptor_loss	1.0000
4:70998066:G:GG	acceptor_gain	1.0000
4:70998066:G:GT	acceptor_loss	1.0000
4:70998066:GCT:G	acceptor_gain	1.0000
4:70998066:GCTGC:G	acceptor_gain	1.0000
4:70998178:TTGAG:T	donor_loss	1.0000
4:70998179:TGAG:T	donor_loss	1.0000
4:70998181:AGGT:A	donor_loss	1.0000
4:70998182:GG:G	donor_loss	1.0000
4:70998184:T:A	donor_loss	1.0000
4:71022351:T:A	acceptor_gain	1.0000
4:71022354:A:AG	acceptor_gain	1.0000
4:71022356:A:AG	acceptor_gain	1.0000
4:71022360:A:AG	acceptor_gain	1.0000
4:71022361:A:G	acceptor_gain	1.0000
4:71022362:AATAG:A	acceptor_gain	1.0000
4:71022363:ATAG:A	acceptor_gain	1.0000
4:71022365:AG:A	acceptor_gain	1.0000
4:71022366:GG:G	acceptor_gain	1.0000
4:71022366:GGA:G	acceptor_gain	1.0000
4:71022560:GGTA:G	donor_loss	1.0000
4:71022561:GTAT:G	donor_loss	1.0000
4:71023582:AT:A	acceptor_gain	1.0000
4:71023583:T:G	acceptor_gain	1.0000
4:71023597:T:G	acceptor_gain	1.0000
4:71023704:GAG:G	donor_gain	1.0000
4:71023704:GAGG:G	donor_loss	1.0000

AlphaMissense

1732 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:71023566:T:C	F137L	0.999
4:71023568:T:A	F137L	0.999
4:71023568:T:G	F137L	0.999
4:71025821:C:G	C185W	0.999
4:70993917:G:A	G28R	0.998
4:70993917:G:C	G28R	0.998
4:70993917:G:T	G28W	0.998
4:70998073:G:A	G33E	0.998
4:70998076:A:T	K34M	0.998
4:70998077:G:C	K34N	0.998
4:70998077:G:T	K34N	0.998
4:70998147:T:A	W58R	0.998
4:70998147:T:C	W58R	0.998
4:71022553:A:C	S132R	0.998
4:71022555:T:A	S132R	0.998
4:71022555:T:G	S132R	0.998
4:70998072:G:T	G33W	0.997
4:70998075:A:C	K34Q	0.997
4:70998149:G:C	W58C	0.997
4:70998149:G:T	W58C	0.997
4:71022433:T:A	W92R	0.997
4:71022433:T:C	W92R	0.997
4:71022470:G:C	R104P	0.997
4:71022539:A:T	E127V	0.997
4:71023690:T:C	L178P	0.997
4:71025829:G:C	R188T	0.997
4:71025909:T:A	W215R	0.997
4:71025909:T:C	W215R	0.997
4:70993918:G:A	G28E	0.996
4:70993922:C:A	N29K	0.996

dbSNP variants (sampled 300 via entrez): RS1000052491 (4:71021321 C>A,T), RS1000102088 (4:71014480 C>G), RS1000265479 (4:70993074 G>A), RS1000277305 (4:70999081 A>G), RS1000322168 (4:71012213 T>A), RS1000324543 (4:70991983 T>C), RS1000403635 (4:71021470 A>G), RS1000403714 (4:70998711 G>A), RS1000600666 (4:70996340 G>C), RS1000605216 (4:70997313 A>G), RS1000648702 (4:71015901 C>T), RS1000670429 (4:70997854 C>A,T), RS1000701247 (4:71015688 G>T), RS1000911536 (4:70996084 C>G), RS1001062441 (4:71001913 A>T)

Disease associations

OMIM: gene MIM:125450 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008758_47	Pre-treatment viral load in HIV-1 infection	8.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010125	viral load

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2447 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,681 (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
CHEMBL230011	TG100-115	2	1,504
CHEMBL1090479	GSK-1070916	1	177

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2306744	Efficacy	3	cytarabine;idarubicin	Leukemia;Myeloid;Acute
rs4694362	Toxicity	3	gemcitabine	Pancreatic Neoplasms
rs66878317	Other	3	gemcitabine
rs80143932	Efficacy	3	cytarabine;idarubicin	Leukemia;Myeloid;Acute

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2306744	DCK	3	2.50	1	cytarabine;idarubicin
rs3775289	DCK		0.00	0
rs4694362	DCK	3	2.50	1	gemcitabine
rs9993633	DCK		0.00	0
rs12648166	DCK		0.00	0
rs66878317	DCK	3	1.00	1	gemcitabine
rs80143932	DCK	3	2.50	1	cytarabine;idarubicin
rs4643786	DCK		0.00	0

ChEMBL bioactivities

195 potent at pChembl≥5 of 200 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	Ki	0.5	nM	CHEMBL2426574
9.30	Ki	0.5	nM	CHEMBL2426570
9.15	IC50	0.7	nM	CHEMBL1081002
9.10	Ki	0.8	nM	CHEMBL2426573
9.05	IC50	0.9	nM	CHEMBL2426567
9.00	IC50	1	nM	CHEMBL1080093
9.00	IC50	1	nM	CHEMBL1081903
8.97	IC50	1.07	nM	CHEMBL2426563
8.94	IC50	1.15	nM	CHEMBL2426570
8.90	IC50	1.25	nM	CHEMBL3358096
8.85	IC50	1.4	nM	CHEMBL2426573
8.84	IC50	1.44	nM	CHEMBL2426573
8.82	Ki	1.5	nM	CHEMBL2426558
8.81	IC50	1.55	nM	CHEMBL2426569
8.77	IC50	1.7	nM	CHEMBL1080444
8.74	Ki	1.8	nM	CHEMBL3358091
8.72	Ki	1.9	nM	CHEMBL2426565
8.70	Ki	2	nM	CHEMBL2426567
8.70	IC50	2	nM	CHEMBL1081904
8.70	EC50	2	nM	CHEMBL1081903
8.61	IC50	2.45	nM	CHEMBL2426562
8.59	IC50	2.59	nM	CHEMBL2426567
8.55	IC50	2.83	nM	CHEMBL2426564
8.54	IC50	2.85	nM	CHEMBL2426572
8.54	IC50	2.9	nM	CHEMBL2426571
8.52	IC50	3	nM	CHEMBL2426558
8.52	IC50	3	nM	CHEMBL1079768
8.52	IC50	3	nM	CHEMBL1081350
8.52	IC50	3	nM	CHEMBL1080443
8.52	IC50	3	nM	CHEMBL1079906
8.52	IC50	3	nM	CHEMBL1080636
8.51	Kd	3.094	nM	CHEMBL5653589
8.51	ED50	3.094	nM	CHEMBL5653589
8.43	IC50	3.7	nM	CHEMBL3358097
8.40	IC50	4	nM	CHEMBL1079379
8.40	IC50	4	nM	CHEMBL1079380
8.40	EC50	4	nM	CHEMBL1080093
8.31	IC50	4.89	nM	CHEMBL2426574
8.31	IC50	4.9	nM	CHEMBL2426574
8.30	IC50	5	nM	CHEMBL1079601
8.30	IC50	5	nM	CHEMBL1080092
8.30	IC50	5	nM	CHEMBL1081727
8.30	EC50	5	nM	CHEMBL1081904
8.30	EC50	5	nM	CHEMBL1081002
8.22	IC50	6	nM	CHEMBL1081901
8.17	Ki	6.8	nM	CHEMBL3358094
8.15	IC50	7	nM	CHEMBL2426598
8.15	IC50	7	nM	CHEMBL3358094
8.10	IC50	8.01	nM	CHEMBL2426566
8.05	Ki	8.9	nM	CHEMBL2426568

PubChem BioAssay actives

193 with measured affinity, of 547 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-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]ethanol	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0005	uM
N-[2-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]ethyl]methanesulfonamide	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0005	uM
2-[6-[4-(4-aminopyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0007	uM
1-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]-2-methylpropan-2-ol	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0008	uM
2-[4-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-(2-hydroxyethoxy)phenoxy]ethanol	1169853: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of [3H]-dC uptake by scintillation counting analysis	ic50	0.0009	uM
3-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxy-4-methoxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0010	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0010	uM
2-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-fluorophenoxy]ethanol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0011	uM
2-[(1R)-1-[2-[3-ethoxy-4-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]-5-methyl-1,3-thiazol-4-yl]ethyl]sulfanylpyrimidine-4,6-diamine	1169853: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of [3H]-dC uptake by scintillation counting analysis	ic50	0.0013	uM
2-[[2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-5-propyl-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-4,6-diamine	770201: Inhibition of dCK (unknown origin) by steady-state kinetic assay	ki	0.0015	uM
3-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]propan-1-ol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0015	uM
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide	467767: Inhibition of human deoxycytidine kinase by lysate filter binding assay	ic50	0.0017	uM
1-[5-[4-[(4-aminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]-2-methylpropan-2-ol	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0018	uM
N-[2-[3-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]phenoxy]ethyl]methanesulfonamide	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0019	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxy-5-methoxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0020	uM
2-[3-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]phenoxy]ethanol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0024	uM
2-[3-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-5-fluorophenoxy]ethanol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0028	uM
2-[5-[4-[(4-aminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]ethanol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0029	uM
1-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]propan-2-ol	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0029	uM
2-[1-[6-(2-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy-5-fluoropyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0030	uM
2-[2-[1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]ethoxy]-5-fluoropyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0030	uM
5-fluoro-2-[1-[6-(2-phenylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0030	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]pyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0030	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]pyrimidin-4-yl]oxy-5-methoxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0030	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148200: Binding affinity to human DCK incubated for 45 mins by Kinobead based pull down assay	kd	0.0031	uM
N-[2-[5-[4-[(1R)-1-(4,6-diaminopyrimidin-2-yl)sulfanylethyl]-5-methyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]ethyl]methanesulfonamide	1169853: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of [3H]-dC uptake by scintillation counting analysis	ic50	0.0037	uM
5-fluoro-2-[1-[5-fluoro-6-(4-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0040	uM
3-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0040	uM
5-fluoro-2-[1-[6-(2-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0050	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-bromopyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0050	uM
4-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-5-fluoropyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0050	uM
5-fluoro-2-[1-[6-(2-fluorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0060	uM
2-[1-[2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-5-methyl-1,3-thiazol-4-yl]ethylsulfanyl]pyrimidine-4,6-diamine	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0068	uM
2-[[5-ethyl-2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-4,6-diamine	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0070	uM
N-[2-[3-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-5-fluorophenoxy]ethyl]methanesulfonamide	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0080	uM
5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenol	1169852: Apparent inhibition of human dCK by steady-state kinetic assay	ki	0.0089	uM
2-[1-[6-(4-chloro-2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy-5-fluoropyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0090	uM
5-fluoro-2-[1-[6-(2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0090	uM
2-[[2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-5-methyl-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-4,6-diamine	770201: Inhibition of dCK (unknown origin) by steady-state kinetic assay	ki	0.0095	uM
2-[1-[2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-5-propyl-1,3-thiazol-4-yl]ethylsulfanyl]pyrimidine-4,6-diamine	1169853: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of [3H]-dC uptake by scintillation counting analysis	ic50	0.0100	uM
2-[1-[6-(2-ethylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy-5-fluoropyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0100	uM
2-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]-2-methylpyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0100	uM
2-[[5-ethyl-2-(3-fluorophenyl)-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-4,6-diamine	770202: Inhibition of dCK in human CCRF-CEM cells assessed as inhibition of tritiated deoxycytidine [3H]-dC uptake	ic50	0.0110	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	1424970: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0120	uM
3-[6-[4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidin-1-yl]pyrimidin-4-yl]oxybenzonitrile	467456: Inhibition of human dCK	ic50	0.0130	uM
2-[1-[6-(4-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy-5-fluoropyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0190	uM
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-3-(2,4-dichlorophenyl)benzenesulfonamide	467767: Inhibition of human deoxycytidine kinase by lysate filter binding assay	ic50	0.0210	uM
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-3-(4-chloro-2-methylphenyl)benzenesulfonamide	467767: Inhibition of human deoxycytidine kinase by lysate filter binding assay	ic50	0.0210	uM
5-fluoro-2-[1-[6-(4-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxypyrimidin-4-amine	467456: Inhibition of human dCK	ic50	0.0210	uM
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)cyclopentyl]-3-(4-chloro-2-methylphenyl)benzamide	467767: Inhibition of human deoxycytidine kinase by lysate filter binding assay	ic50	0.0210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression, affects expression	3
bisphenol A	decreases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	decreases response to substance, increases expression	2
Cytarabine	affects binding, decreases response to substance	2
Tretinoin	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(2-butoxyethyl) phosphate	increases expression	1
arsenite	affects binding, decreases reaction	1
tanshinone	increases expression	1
2’-deoxycytidine 5’-triphosphate	increases metabolic processing	1
3’-amino-2’,3’-dideoxycytidine	affects binding	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
fenpyroximate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
2’-C-methylcytidine	increases phosphorylation	1
dorsomorphin	affects cotreatment, decreases expression	1
Emtricitabine	increases activity, increases phosphorylation, affects binding	1

ChEMBL screening assays

54 unique, capped per target: 49 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1064146	Binding	Ratio of Kcat to Km for cloned 2’-deoxycytidine kinase in human HepG2 cells assessed as formation of formation of PS-6130 monophosphate by spectrophotometry	The mechanism of action of beta-D-2’-deoxy-2’-fluoro-2’-C-methylcytidine involves a second metabolic pathway leading to beta-D-2’-deoxy-2’-fluoro-2’-C-methyluridine 5’-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. — Antimicrob Agents Chemother
CHEMBL3538236	ADMET	Activity of human recombinant N-terminal His-tagged wild type DCK expressed in Escherichia coli BL21(DE3) cells assessed as enzyme-mediated 2’,2’-difluorodeoxycytidine formation incubated for 1 min by liquid chromatography-tandem mass spect	Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidine deaminase and deoxycytidine kinase. — Drug Metab Dispos

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1W1	Abcam A-549 DCK KO	Cancer cell line	Male
CVCL_D2AG	Abcam HCT 116 DCK KO	Cancer cell line	Male
CVCL_D2NB	Abcam THP-1 DCK KO	Cancer cell line	Male
CVCL_QZ54	RDLD-1	Cancer cell line	Male
CVCL_SK45	HAP1 DCK (-) 1	Cancer cell line	Male
CVCL_XN15	HAP1 DCK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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