UCK2

gene
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Summary

UCK2 (uridine-cytidine kinase 2, HGNC:12562) is a protein-coding gene on chromosome 1q24.1, encoding Uridine-cytidine kinase 2 (Q9BZX2). Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate.

This gene encodes a pyrimidine ribonucleoside kinase. The encoded protein (EC 2.7.1.48) catalyzes phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively.

Source: NCBI Gene 7371 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 30 total
  • Druggable target: yes
  • MANE Select transcript: NM_012474

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12562
Approved symbolUCK2
Nameuridine-cytidine kinase 2
Location1q24.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000143179
Ensembl biotypeprotein_coding
OMIM609329
Entrez7371

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000367879, ENST00000462329, ENST00000463772, ENST00000464197, ENST00000469256, ENST00000470820, ENST00000475333, ENST00000479872, ENST00000642653, ENST00000940421

RefSeq mRNA: 2 — MANE Select: NM_012474 NM_001363568, NM_012474

CCDS: CCDS1252, CCDS86027

Canonical transcript exons

ENST00000367879 — 7 exons

ExonStartEnd
ENSE00000958515165891226165891322
ENSE00001445845165827614165827932
ENSE00001656332165890204165890363
ENSE00003474372165907684165911618
ENSE00003674537165896190165896332
ENSE00003708517165903182165903279
ENSE00003711094165905921165905969

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 93.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9980 / max 503.0526, expressed in 1815 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter IDTPM avgSamples expressed
639825.53091797
63977.12151617
64005.45301622
63993.42181460
64051.1060358
64060.541547
64020.263062
64070.258586
64030.169460
64040.132451

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499193.66gold quality
ventricular zoneUBERON:000305391.47gold quality
ganglionic eminenceUBERON:000402390.94gold quality
embryoUBERON:000092290.14gold quality
stromal cell of endometriumCL:000225589.73gold quality
cortical plateUBERON:000534389.69gold quality
placentaUBERON:000198789.14gold quality
rectumUBERON:000105288.58gold quality
esophagus mucosaUBERON:000246988.51gold quality
lower esophagus mucosaUBERON:003583487.95gold quality
cartilage tissueUBERON:000241887.44gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.83gold quality
minor salivary glandUBERON:000183086.70gold quality
transverse colonUBERON:000115786.29gold quality
skin of abdomenUBERON:000141686.12gold quality
body of pancreasUBERON:000115085.98gold quality
mouth mucosaUBERON:000372985.89gold quality
skin of legUBERON:000151185.55gold quality
islet of LangerhansUBERON:000000685.51gold quality
body of stomachUBERON:000116185.47gold quality
small intestine Peyer’s patchUBERON:000345485.37gold quality
secondary oocyteCL:000065585.25gold quality
esophagusUBERON:000104385.24gold quality
gastrocnemiusUBERON:000138885.19gold quality
oocyteCL:000002385.16gold quality
gingival epitheliumUBERON:000194985.12gold quality
ileal mucosaUBERON:000033185.00gold quality
gingivaUBERON:000182884.72gold quality
saliva-secreting glandUBERON:000104484.60gold quality
ascending aortaUBERON:000149684.47gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes8.68
E-MTAB-6142no67.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1

miRNA regulators (miRDB)

127 targeting UCK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-548AN99.9770.912817
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-MIR-6888-3P99.9765.951170
HSA-MIR-426799.9666.532368
HSA-MIR-493-5P99.9672.472382
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-96-5P99.9572.802140
HSA-MIR-391099.9571.132227
HSA-MIR-144-3P99.9473.982698
HSA-MIR-101-3P99.9475.032230
HSA-MIR-1236-3P99.9468.041695
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-1213399.9271.822006
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-129799.9173.413162
HSA-MIR-1271-5P99.9171.991972
HSA-MIR-130599.9171.433443
HSA-MIR-345-3P99.8970.231421

Literature-anchored findings (GeneRIF, showing 14)

  • Increased intranuclear levels of UK may contribute to the metabolic build-up that is needed for Epstein-Barr virus nuclear protein EBNA-3-mediated B-cell blast transformation and rapid proliferation. (PMID:12199906)
  • UCK2 is responsible for phosphorylation and activation of the antitumor activity of 3’-ethynyl nucleosides 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine. (PMID:15280220)
  • gene mapped to chromosome 1. (PMID:16484797)
  • B4GALT3, DAP3, RGS16, TMEM183A and UCK2–were significantly overexpressed in dup(1q)-positive ALLs compared with high hyperdiploid ALLs without dup(1q). (PMID:17613536)
  • The mechanism of phosphate transfer in UCK2 is shown to be concerted, and is accompanied by concerted proton transfer from the 5’-hydroxyl to a conserved active site aspartic acid that serves as a catalytic base (PMID:19532987)
  • Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23. (PMID:23462292)
  • Knockdown of endogenous UCK2 as well as overexpression of UCK1 resulted in decreased metabolism of uridine and cytidine and protected neuroblastoma cells from 3-deazauridine-induced toxicity. Subcellular localization studies showed that UCK1-GFP and UCK2-GFP were localized in the cell nucleus and cytosol, respectively. (PMID:27239701)
  • accumulation of RX-3117 nucleotides correlated with UCK2 expression. (PMID:27612203)
  • UCK1 and 2 are both expressed in several neuroblastoma cell lines, including four MYCN single copy cell lines and five MYCN amplified cell lines (PMID:27906629)
  • survival analysis showed that only high methylation of cg0927774 was associated with better OS and RFS of HCC patients. Based on the findings above, we infer that UCK2 upregulation might be a valuable prognostic marker in hepatocellular carcinoma. The methylation of status cg0927774 might play a critical role in its expression (PMID:30304569)
  • High UCK2 expression is associated with hepatocellular carcinoma aggressiveness. (PMID:30556610)
  • Lung cancer patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Cytology experiments show that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. Study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer. (PMID:31278886)
  • Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma. (PMID:36447138)
  • Cytotoxic Flavokawain B Inhibits the Growth and Metastasis of Hepatocellular Carcinoma through UCK2 Modulation of the STAT3/Hif-1alpha/VEGF Signalling Pathway. (PMID:37534791)

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
danio_reriouck2aENSDARG00000006074
danio_reriouck2bENSDARG00000022213
mus_musculusUck2ENSMUSG00000026558
rattus_norvegicusUck2ENSRNOG00000003917
drosophila_melanogasterUckFBGN0263398
caenorhabditis_elegansWBGENE00007089

Paralogs (3): UPRT (ENSG00000094841), UCK1 (ENSG00000130717), UCKL1 (ENSG00000198276)

Protein

Protein identifiers

Uridine-cytidine kinase 2Q9BZX2 (reviewed: Q9BZX2)

Alternative names: Cytidine monophosphokinase 2, Testis-specific protein TSA903, Uridine monophosphokinase 2

All UniProt accessions (2): Q9BZX2, A0A2R8Y653

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate. Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor. Can also phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine.

Subunit / interactions. Homotetramer.

Tissue specificity. According to PubMed:8812458; testis-specific. According to PubMed:11306702, placenta-specific.

Pathway. Pyrimidine metabolism; CTP biosynthesis via salvage pathway; CTP from cytidine: step 1/3. Pyrimidine metabolism; UMP biosynthesis via salvage pathway; UMP from uridine: step 1/1.

Similarity. Belongs to the uridine kinase family.

Isoforms (2)

UniProt IDNamesCanonical?
Q9BZX2-11yes
Q9BZX2-22

RefSeq proteins (2): NP_001350497, NP_036606* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000764Uridine_kinase-likeFamily
IPR006083PRK/URKDomain
IPR027417P-loop_NTPaseHomologous_superfamily

Pfam: PF00485

Enzyme classification (BRENDA):

  • EC 2.7.1.48 — uridine/cytidine kinase (BRENDA: 11 organisms, 140 substrates, 53 inhibitors, 88 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
CYTIDINE0.023–438
URIDINE0.04–11.531
ATP0.062–510
5-FLUOROURIDINE0.03–0.0692
3-DEAZAURIDINE0.21
5-AZACYTIDINE111
6-AZAURIDINE0.341

Catalyzed reactions (Rhea), 2 shown:

  • uridine + ATP = UMP + ADP + H(+) (RHEA:16825)
  • cytidine + ATP = CMP + ADP + H(+) (RHEA:24674)

UniProt features (41 total): helix 14, binding site 8, strand 7, modified residue 2, sequence conflict 2, region of interest 2, turn 2, initiator methionine 1, chain 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

11 structures.

PDBMethodResolution (Å)
1UJ2X-RAY DIFFRACTION1.8
1XRJX-RAY DIFFRACTION2
7SQLX-RAY DIFFRACTION2.4
6N54X-RAY DIFFRACTION2.42
1UFQX-RAY DIFFRACTION2.5
1UDWX-RAY DIFFRACTION2.6
1UEIX-RAY DIFFRACTION2.6
1UEJX-RAY DIFFRACTION2.61
6N53X-RAY DIFFRACTION2.7
6PWZX-RAY DIFFRACTION3
6N55X-RAY DIFFRACTION3.08

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BZX2-F186.520.81

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 (8): 176; 184; 213; 27–35; 84; 112; 117; 166

Post-translational modifications (2): 2, 254

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-73614Pyrimidine salvage

MSigDB gene sets: 346 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BASSO_B_LYMPHOCYTE_NETWORK, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP

GO Biological Process (6): feeding behavior (GO:0007631), UMP salvage (GO:0044206), CTP salvage (GO:0044211), response to axon injury (GO:0048678), cellular response to oxygen levels (GO:0071453), CMP biosynthetic process (GO:0009224)

GO Molecular Function (7): uridine kinase activity (GO:0004849), ATP binding (GO:0005524), identical protein binding (GO:0042802), cytidine kinase activity (GO:0043771), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Nucleotide salvage1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
UMP biosynthetic process2
pyrimidine ribonucleotide salvage2
nucleoside kinase activity2
cellular anatomical structure2
behavior1
CTP biosynthetic process1
response to wounding1
response to oxygen levels1
cellular response to chemical stimulus1
pyrimidine ribonucleoside monophosphate biosynthetic process1
pyrimidine ribonucleotide biosynthetic process1
CMP metabolic process1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
protein binding1
CMP biosynthetic process1
nucleoside phosphate binding1
heterocyclic compound binding1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
intracellular anatomical structure1
cytoplasm1

Protein interactions and networks

STRING

2231 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
UCK2PASKQ96RG2891
UCK2CMPK1P30085799
UCK2UMPSP11172768
UCK2PPP1R7Q15435764
UCK2UPP2O95045763
UCK2UPP1Q16831754
UCK2TYMSP04818739
UCK2TK1P04183692
UCK2UPRTQ96BW1683
UCK2GYS1P13807662
UCK2DCKP27707608
UCK2DTYMKP23919584
UCK2RNF19BQ6ZMZ0577
UCK2CDAP32320575
UCK2TYMPP19971563

IntAct

59 interactions, top by confidence:

ABTypeScore
MED20MED19psi-mi:“MI:0914”(association)0.840
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
UCK2UCK2psi-mi:“MI:0915”(physical association)0.560
UPRTSERPINB4psi-mi:“MI:0914”(association)0.530
UCK2IAH1psi-mi:“MI:0914”(association)0.530
TNFSF8LGALS8psi-mi:“MI:0914”(association)0.530
UPRTUCK2psi-mi:“MI:0914”(association)0.530
LPAR1TMEM223psi-mi:“MI:0914”(association)0.530
KSR1FBLL1psi-mi:“MI:0914”(association)0.350
DLDNFKBIEpsi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350
Mpsi-mi:“MI:0914”(association)0.350
AGPSpsi-mi:“MI:0914”(association)0.350
TLK2IGKV1D-13psi-mi:“MI:0914”(association)0.350
ATG16L1ESYT2psi-mi:“MI:0914”(association)0.350
GPR45VWA8psi-mi:“MI:0914”(association)0.350
OPALINFAM171A2psi-mi:“MI:0914”(association)0.350
MFSD4AUBXN8psi-mi:“MI:0914”(association)0.350
PROKR1TNFRSF10Bpsi-mi:“MI:0914”(association)0.350
F2RL1TNPO2psi-mi:“MI:0914”(association)0.350
CACNG7PLD2psi-mi:“MI:0914”(association)0.350
CACNG4TTI1psi-mi:“MI:0914”(association)0.350
WDTC1PHGDHpsi-mi:“MI:0914”(association)0.350
UCK2DCAF6psi-mi:“MI:0914”(association)0.350
AFG2BMMP24OSpsi-mi:“MI:0914”(association)0.350
ARMC6DDX39Apsi-mi:“MI:0914”(association)0.350

BioGRID (82): UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), UCK1 (Affinity Capture-MS), UCKL1 (Affinity Capture-MS), IAH1 (Affinity Capture-MS), VARS2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-RNA), UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), AKT1 (Affinity Capture-Western), UCK2 (Positive Genetic)

ESM2 similar proteins: A4IFD0, A4IG62, A7GT59, B1H116, B5FG51, C0ZAS6, O00763, O23617, P16118, P32232, P49872, P52623, P70266, Q0P5A4, Q13057, Q4R4K2, Q5E3Z9, Q5EBA1, Q5R9C1, Q5T6J7, Q5VV42, Q66I71, Q6AY55, Q6GPD9, Q6P4Y0, Q6PA79, Q7L5N7, Q7SYM0, Q7ZV79, Q80YD1, Q8IYB8, Q8MIR4, Q8T154, Q8WV93, Q91309, Q91348, Q91WE6, Q91YL3, Q920P5, Q99PM9

Diamond homologs: A0Q140, A2RDZ9, A2RJB4, A4IR72, A5ITD6, A5VKU8, A6QHF2, A6TR08, A6U280, A7GGE1, A7GT59, A7X320, A7Z727, A8AWT2, A8FFL8, A8YU29, A8Z4E9, A9WCC8, B1H116, B1IJ68, B1KXA7, B1MXP1, B2G882, B4U220, B5XM21, B7GIU0, B8G8N0, B9DNJ4, B9DSN2, B9E6Y9, B9LED5, C0M9M0, C0MCM8, C0ZAS6, C1FSX6, C3L140, C5D4Y5, O32033, O65583, O74427

SIGNOR signaling

9 interactions.

AEffectBMechanism
UCK2“down-regulates quantity”ATP(4-)“chemical modification”
UCK2“up-regulates quantity”ADP(3-)“chemical modification”
UCK2“down-regulates quantity”cytidine“chemical modification”
UCK2“up-regulates quantity”“cytidine 5’-monophosphate(2-)”“chemical modification”
UCK2“down-regulates quantity”uridine“chemical modification”
UCK2“up-regulates quantity”“uridine 5’-monophosphate(2-)”“chemical modification”
METTL3“up-regulates quantity by stabilization”UCK2“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance17
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1651 predictions. Top by Δscore:

VariantEffectΔscore
1:165890201:C:Gacceptor_gain1.0000
1:165890202:A:AGacceptor_gain1.0000
1:165890203:G:GGacceptor_gain1.0000
1:165890203:GTCTT:Gacceptor_gain1.0000
1:165890362:GG:Gdonor_gain1.0000
1:165890363:GG:Gdonor_gain1.0000
1:165891220:TTTCA:Tacceptor_loss1.0000
1:165891221:TTCA:Tacceptor_loss1.0000
1:165891222:TCA:Tacceptor_loss1.0000
1:165891223:CAGAT:Cacceptor_loss1.0000
1:165891224:A:AGacceptor_gain1.0000
1:165891224:AG:Aacceptor_loss1.0000
1:165891225:G:GCacceptor_gain1.0000
1:165891225:GAT:Gacceptor_gain1.0000
1:165903276:GCCA:Gdonor_gain1.0000
1:165903280:G:GGdonor_gain1.0000
1:165905915:CCACA:Cacceptor_loss1.0000
1:165905916:CACA:Cacceptor_loss1.0000
1:165905917:ACAG:Aacceptor_loss1.0000
1:165905918:CA:Cacceptor_loss1.0000
1:165905919:A:AGacceptor_gain1.0000
1:165905920:G:GCacceptor_gain1.0000
1:165905920:GAC:Gacceptor_gain1.0000
1:165905968:GG:Gdonor_gain1.0000
1:165905969:GG:Gdonor_gain1.0000
1:165907682:A:AGacceptor_gain1.0000
1:165907682:AGT:Aacceptor_gain1.0000
1:165907683:G:GGacceptor_gain1.0000
1:165907683:GT:Gacceptor_gain1.0000
1:165907683:GTG:Gacceptor_gain1.0000

AlphaMissense

1721 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:165896239:G:AG136R1.000
1:165896239:G:CG136R1.000
1:165896293:T:CF154L1.000
1:165896295:T:AF154L1.000
1:165896295:T:GF154L1.000
1:165896311:G:CD160H1.000
1:165896321:T:CL163P1.000
1:165903268:T:CF196L1.000
1:165903270:C:AF196L1.000
1:165903270:C:GF196L1.000
1:165905934:C:AA204D1.000
1:165907696:T:CL220P1.000
1:165827904:G:AG24D0.999
1:165827912:G:AG27R0.999
1:165827912:G:CG27R0.999
1:165827912:G:TG27W0.999
1:165827913:G:AG27E0.999
1:165827915:G:AG28R0.999
1:165827915:G:CG28R0.999
1:165827924:A:CS31R0.999
1:165827926:C:AS31R0.999
1:165827926:C:GS31R0.999
1:165827927:G:CG32R0.999
1:165827928:G:AG32D0.999
1:165827928:G:TG32V0.999
1:165890294:T:CF64L0.999
1:165890296:C:AF64L0.999
1:165890296:C:GF64L0.999
1:165890350:C:AN82K0.999
1:165890350:C:GN82K0.999

dbSNP variants (sampled 300 via entrez): RS1000000607 (1:165851595 G>C), RS1000026347 (1:165831236 G>A), RS1000066710 (1:165859978 G>A), RS1000136715 (1:165892884 G>A), RS1000166298 (1:165855523 T>C), RS1000187128 (1:165911870 T>A), RS1000215890 (1:165855753 G>A), RS1000219144 (1:165894432 C>T), RS1000221538 (1:165849004 C>T), RS1000235743 (1:165886299 C>G), RS1000331180 (1:165839882 T>C), RS1000348389 (1:165857740 C>A), RS1000406161 (1:165839763 G>A), RS1000426324 (1:165842882 C>A,T), RS1000431840 (1:165843334 T>C)

Disease associations

OMIM: gene MIM:609329 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST002022_12Testicular germ cell tumor2.000000e-08
GCST002023_7Testicular germ cell tumor6.000000e-06
GCST002855_4Testicular germ cell tumor2.000000e-07
GCST004635_3Testicular germ cell tumor5.000000e-11
GCST004713_14Testicular germ cell tumor2.000000e-14
GCST009597_237Multiple sclerosis8.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2469 (SINGLE PROTEIN), CHEMBL3542438 (PROTEIN FAMILY), CHEMBL4748231 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 17 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.00Ki1000nMCHEMBL1592234
5.52IC503000nMCHEMBL1592234
5.46Ki3500nMCHEMBL1592234
5.42IC503800nMCHEMBL1592234
5.33IC504700nMCHEMBL4588628
5.04IC509200nMCHEMBL4553820

PubChem BioAssay actives

6 with measured affinity, of 65 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
3-[[2-[[9-methyl-2-(4-methylphenyl)-5H-chromeno[2,3-d]pyrimidin-4-yl]sulfanyl]acetyl]amino]benzoic acid1589138: Non-competitive inhibition of C-terminally His6-tagged human UCK2 expressed in Escherichia coli BL21(DE3) cells using uridine, phosphoenolpyruvate, NADH and varying ATP level by spectrophotometry based pyruvate kinase and lactate dehydrogenase coupled enzyme assayki1.0000uM
3-[[2-[(9-methyl-2-phenyl-5H-chromeno[2,3-d]pyrimidin-4-yl)sulfanyl]acetyl]amino]benzoic acid1589134: Inhibition of C-terminally His6-tagged human UCK2 expressed in Escherichia coli BL21(DE3) cells incubated for 15 mins before ATP addition and measured after 60 mins by ADP-Glo kinase assayic504.7000uM
N-(4-bromophenyl)-2-[[1-(4-fluorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]acetamide1589135: Inhibition of C-terminally His6-tagged human UCK2 expressed in Escherichia coli BL21(DE3) cells incubated for 15 mins before ATP addition and measured after 60 mins by ADP-Glo kinase assay based HTS assayic509.2000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, increases expression, affects cotreatment4
Estradiolincreases expression3
sodium arsenitedecreases expression, increases expression2
Fluorouracildecreases expression, affects response to substance2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases expression2
Cyclosporineincreases expression2
Aflatoxin B1increases expression2
Cadmium Chloridedecreases expression, increases expression2
GSK-J4decreases expression1
afuresertibdecreases expression1
methylmercuric chlorideincreases expression1
triphenyl phosphateaffects expression1
methylselenic aciddecreases expression1
trichostatin Aaffects expression1
cobaltous chloridedecreases expression1
benzo(e)pyreneincreases methylation1
2,3-bis(3’-hydroxybenzyl)butyrolactoneaffects cotreatment, increases expression1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic aciddecreases expression1
CGP 52608affects binding, increases reaction1
abrinedecreases expression1
2’-C-methylcytidinedecreases phosphorylation, increases phosphorylation1
(+)-JQ1 compounddecreases expression1
Resveratrolaffects cotreatment, increases expression1
Atrazineincreases expression1
Benzo(a)pyreneincreases methylation1
Benzoatesdecreases expression1
Calcitrioldecreases expression, affects cotreatment1
Carbamazepineaffects expression1
Coumestrolaffects cotreatment, increases expression1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4387679BindingInhibition of C-terminally His6-tagged human UCK2 expressed in Escherichia coli BL21(DE3) cells incubated for 15 mins before ATP addition and measured after 60 mins by ADP-Glo kinase assayDiscovery of small molecule inhibitors of human uridine-cytidine kinase 2 by high-throughput screening. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_XU88HAP1 UCK2 (-)Cancer cell lineMale

Clinical trials (associated diseases)

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