UCK2
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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
| Field | Value |
|---|---|
| HGNC ID | HGNC:12562 |
| Approved symbol | UCK2 |
| Name | uridine-cytidine kinase 2 |
| Location | 1q24.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000143179 |
| Ensembl biotype | protein_coding |
| OMIM | 609329 |
| Entrez | 7371 |
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
| Exon | Start | End |
|---|---|---|
| ENSE00000958515 | 165891226 | 165891322 |
| ENSE00001445845 | 165827614 | 165827932 |
| ENSE00001656332 | 165890204 | 165890363 |
| ENSE00003474372 | 165907684 | 165911618 |
| ENSE00003674537 | 165896190 | 165896332 |
| ENSE00003708517 | 165903182 | 165903279 |
| ENSE00003711094 | 165905921 | 165905969 |
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 ID | TPM avg | Samples expressed |
|---|---|---|
| 6398 | 25.5309 | 1797 |
| 6397 | 7.1215 | 1617 |
| 6400 | 5.4530 | 1622 |
| 6399 | 3.4218 | 1460 |
| 6405 | 1.1060 | 358 |
| 6406 | 0.5415 | 47 |
| 6402 | 0.2630 | 62 |
| 6407 | 0.2585 | 86 |
| 6403 | 0.1694 | 60 |
| 6404 | 0.1324 | 51 |
Top tissues by expression
275 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| mucosa of transverse colon | UBERON:0004991 | 93.66 | gold quality |
| ventricular zone | UBERON:0003053 | 91.47 | gold quality |
| ganglionic eminence | UBERON:0004023 | 90.94 | gold quality |
| embryo | UBERON:0000922 | 90.14 | gold quality |
| stromal cell of endometrium | CL:0002255 | 89.73 | gold quality |
| cortical plate | UBERON:0005343 | 89.69 | gold quality |
| placenta | UBERON:0001987 | 89.14 | gold quality |
| rectum | UBERON:0001052 | 88.58 | gold quality |
| esophagus mucosa | UBERON:0002469 | 88.51 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 87.95 | gold quality |
| cartilage tissue | UBERON:0002418 | 87.44 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 86.83 | gold quality |
| minor salivary gland | UBERON:0001830 | 86.70 | gold quality |
| transverse colon | UBERON:0001157 | 86.29 | gold quality |
| skin of abdomen | UBERON:0001416 | 86.12 | gold quality |
| body of pancreas | UBERON:0001150 | 85.98 | gold quality |
| mouth mucosa | UBERON:0003729 | 85.89 | gold quality |
| skin of leg | UBERON:0001511 | 85.55 | gold quality |
| islet of Langerhans | UBERON:0000006 | 85.51 | gold quality |
| body of stomach | UBERON:0001161 | 85.47 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 85.37 | gold quality |
| secondary oocyte | CL:0000655 | 85.25 | gold quality |
| esophagus | UBERON:0001043 | 85.24 | gold quality |
| gastrocnemius | UBERON:0001388 | 85.19 | gold quality |
| oocyte | CL:0000023 | 85.16 | gold quality |
| gingival epithelium | UBERON:0001949 | 85.12 | gold quality |
| ileal mucosa | UBERON:0000331 | 85.00 | gold quality |
| gingiva | UBERON:0001828 | 84.72 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 84.60 | gold quality |
| ascending aorta | UBERON:0001496 | 84.47 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 8.68 |
| E-MTAB-6142 | no | 67.71 |
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):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-34A-5P | 99.99 | 71.21 | 1784 |
| HSA-MIR-449A | 99.99 | 71.05 | 1776 |
| HSA-MIR-3667-3P | 99.99 | 67.17 | 1636 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-548AN | 99.97 | 70.91 | 2817 |
| HSA-MIR-34C-5P | 99.97 | 70.45 | 1577 |
| HSA-MIR-449B-5P | 99.97 | 70.26 | 1580 |
| HSA-MIR-6888-3P | 99.97 | 65.95 | 1170 |
| HSA-MIR-4267 | 99.96 | 66.53 | 2368 |
| HSA-MIR-493-5P | 99.96 | 72.47 | 2382 |
| HSA-MIR-551B-5P | 99.96 | 71.28 | 3493 |
| HSA-MIR-1468-3P | 99.96 | 72.74 | 3797 |
| HSA-MIR-96-5P | 99.95 | 72.80 | 2140 |
| HSA-MIR-3910 | 99.95 | 71.13 | 2227 |
| HSA-MIR-144-3P | 99.94 | 73.98 | 2698 |
| HSA-MIR-101-3P | 99.94 | 75.03 | 2230 |
| HSA-MIR-1236-3P | 99.94 | 68.04 | 1695 |
| HSA-MIR-6721-5P | 99.93 | 68.92 | 2981 |
| HSA-MIR-12133 | 99.92 | 71.82 | 2006 |
| HSA-MIR-515-5P | 99.92 | 69.82 | 2343 |
| HSA-MIR-519E-5P | 99.92 | 69.62 | 2358 |
| HSA-MIR-1297 | 99.91 | 73.41 | 3162 |
| HSA-MIR-1271-5P | 99.91 | 71.99 | 1972 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-345-3P | 99.89 | 70.23 | 1421 |
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
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | uck2a | ENSDARG00000006074 |
| danio_rerio | uck2b | ENSDARG00000022213 |
| mus_musculus | Uck2 | ENSMUSG00000026558 |
| rattus_norvegicus | Uck2 | ENSRNOG00000003917 |
| drosophila_melanogaster | Uck | FBGN0263398 |
| caenorhabditis_elegans | WBGENE00007089 |
Paralogs (3): UPRT (ENSG00000094841), UCK1 (ENSG00000130717), UCKL1 (ENSG00000198276)
Protein
Protein identifiers
Uridine-cytidine kinase 2 — Q9BZX2 (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 ID | Names | Canonical? |
|---|---|---|
| Q9BZX2-1 | 1 | yes |
| Q9BZX2-2 | 2 |
RefSeq proteins (2): NP_001350497, NP_036606* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000764 | Uridine_kinase-like | Family |
| IPR006083 | PRK/URK | Domain |
| IPR027417 | P-loop_NTPase | Homologous_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.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| CYTIDINE | 0.023–4 | 38 |
| URIDINE | 0.04–11.5 | 31 |
| ATP | 0.062–5 | 10 |
| 5-FLUOROURIDINE | 0.03–0.069 | 2 |
| 3-DEAZAURIDINE | 0.2 | 1 |
| 5-AZACYTIDINE | 11 | 1 |
| 6-AZAURIDINE | 0.34 | 1 |
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.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 1UJ2 | X-RAY DIFFRACTION | 1.8 |
| 1XRJ | X-RAY DIFFRACTION | 2 |
| 7SQL | X-RAY DIFFRACTION | 2.4 |
| 6N54 | X-RAY DIFFRACTION | 2.42 |
| 1UFQ | X-RAY DIFFRACTION | 2.5 |
| 1UDW | X-RAY DIFFRACTION | 2.6 |
| 1UEI | X-RAY DIFFRACTION | 2.6 |
| 1UEJ | X-RAY DIFFRACTION | 2.61 |
| 6N53 | X-RAY DIFFRACTION | 2.7 |
| 6PWZ | X-RAY DIFFRACTION | 3 |
| 6N55 | X-RAY DIFFRACTION | 3.08 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9BZX2-F1 | 86.52 | 0.81 |
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
| ID | Pathway |
|---|---|
| R-HSA-73614 | Pyrimidine 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:
| Category | Pathways |
|---|---|
| Nucleotide salvage | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| UMP biosynthetic process | 2 |
| pyrimidine ribonucleotide salvage | 2 |
| nucleoside kinase activity | 2 |
| cellular anatomical structure | 2 |
| behavior | 1 |
| CTP biosynthetic process | 1 |
| response to wounding | 1 |
| response to oxygen levels | 1 |
| cellular response to chemical stimulus | 1 |
| pyrimidine ribonucleoside monophosphate biosynthetic process | 1 |
| pyrimidine ribonucleotide biosynthetic process | 1 |
| CMP metabolic process | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| protein binding | 1 |
| CMP biosynthetic process | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| catalytic activity | 1 |
| intracellular anatomical structure | 1 |
| cytoplasm | 1 |
Protein interactions and networks
STRING
2231 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| UCK2 | PASK | Q96RG2 | 891 |
| UCK2 | CMPK1 | P30085 | 799 |
| UCK2 | UMPS | P11172 | 768 |
| UCK2 | PPP1R7 | Q15435 | 764 |
| UCK2 | UPP2 | O95045 | 763 |
| UCK2 | UPP1 | Q16831 | 754 |
| UCK2 | TYMS | P04818 | 739 |
| UCK2 | TK1 | P04183 | 692 |
| UCK2 | UPRT | Q96BW1 | 683 |
| UCK2 | GYS1 | P13807 | 662 |
| UCK2 | DCK | P27707 | 608 |
| UCK2 | DTYMK | P23919 | 584 |
| UCK2 | RNF19B | Q6ZMZ0 | 577 |
| UCK2 | CDA | P32320 | 575 |
| UCK2 | TYMP | P19971 | 563 |
IntAct
59 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| MED20 | MED19 | psi-mi:“MI:0914”(association) | 0.840 |
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| UCK2 | UCK2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| UPRT | SERPINB4 | psi-mi:“MI:0914”(association) | 0.530 |
| UCK2 | IAH1 | psi-mi:“MI:0914”(association) | 0.530 |
| TNFSF8 | LGALS8 | psi-mi:“MI:0914”(association) | 0.530 |
| UPRT | UCK2 | psi-mi:“MI:0914”(association) | 0.530 |
| LPAR1 | TMEM223 | psi-mi:“MI:0914”(association) | 0.530 |
| KSR1 | FBLL1 | psi-mi:“MI:0914”(association) | 0.350 |
| DLD | NFKBIE | psi-mi:“MI:0914”(association) | 0.350 |
| LRRK2 | psi-mi:“MI:0914”(association) | 0.350 | |
| M | psi-mi:“MI:0914”(association) | 0.350 | |
| AGPS | psi-mi:“MI:0914”(association) | 0.350 | |
| TLK2 | IGKV1D-13 | psi-mi:“MI:0914”(association) | 0.350 |
| ATG16L1 | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
| GPR45 | VWA8 | psi-mi:“MI:0914”(association) | 0.350 |
| OPALIN | FAM171A2 | psi-mi:“MI:0914”(association) | 0.350 |
| MFSD4A | UBXN8 | psi-mi:“MI:0914”(association) | 0.350 |
| PROKR1 | TNFRSF10B | psi-mi:“MI:0914”(association) | 0.350 |
| F2RL1 | TNPO2 | psi-mi:“MI:0914”(association) | 0.350 |
| CACNG7 | PLD2 | psi-mi:“MI:0914”(association) | 0.350 |
| CACNG4 | TTI1 | psi-mi:“MI:0914”(association) | 0.350 |
| WDTC1 | PHGDH | psi-mi:“MI:0914”(association) | 0.350 |
| UCK2 | DCAF6 | psi-mi:“MI:0914”(association) | 0.350 |
| AFG2B | MMP24OS | psi-mi:“MI:0914”(association) | 0.350 |
| ARMC6 | DDX39A | psi-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.
| A | Effect | B | Mechanism |
|---|---|---|---|
| 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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 17 |
| Likely benign | 1 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1651 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:165890201:C:G | acceptor_gain | 1.0000 |
| 1:165890202:A:AG | acceptor_gain | 1.0000 |
| 1:165890203:G:GG | acceptor_gain | 1.0000 |
| 1:165890203:GTCTT:G | acceptor_gain | 1.0000 |
| 1:165890362:GG:G | donor_gain | 1.0000 |
| 1:165890363:GG:G | donor_gain | 1.0000 |
| 1:165891220:TTTCA:T | acceptor_loss | 1.0000 |
| 1:165891221:TTCA:T | acceptor_loss | 1.0000 |
| 1:165891222:TCA:T | acceptor_loss | 1.0000 |
| 1:165891223:CAGAT:C | acceptor_loss | 1.0000 |
| 1:165891224:A:AG | acceptor_gain | 1.0000 |
| 1:165891224:AG:A | acceptor_loss | 1.0000 |
| 1:165891225:G:GC | acceptor_gain | 1.0000 |
| 1:165891225:GAT:G | acceptor_gain | 1.0000 |
| 1:165903276:GCCA:G | donor_gain | 1.0000 |
| 1:165903280:G:GG | donor_gain | 1.0000 |
| 1:165905915:CCACA:C | acceptor_loss | 1.0000 |
| 1:165905916:CACA:C | acceptor_loss | 1.0000 |
| 1:165905917:ACAG:A | acceptor_loss | 1.0000 |
| 1:165905918:CA:C | acceptor_loss | 1.0000 |
| 1:165905919:A:AG | acceptor_gain | 1.0000 |
| 1:165905920:G:GC | acceptor_gain | 1.0000 |
| 1:165905920:GAC:G | acceptor_gain | 1.0000 |
| 1:165905968:GG:G | donor_gain | 1.0000 |
| 1:165905969:GG:G | donor_gain | 1.0000 |
| 1:165907682:A:AG | acceptor_gain | 1.0000 |
| 1:165907682:AGT:A | acceptor_gain | 1.0000 |
| 1:165907683:G:GG | acceptor_gain | 1.0000 |
| 1:165907683:GT:G | acceptor_gain | 1.0000 |
| 1:165907683:GTG:G | acceptor_gain | 1.0000 |
AlphaMissense
1721 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:165896239:G:A | G136R | 1.000 |
| 1:165896239:G:C | G136R | 1.000 |
| 1:165896293:T:C | F154L | 1.000 |
| 1:165896295:T:A | F154L | 1.000 |
| 1:165896295:T:G | F154L | 1.000 |
| 1:165896311:G:C | D160H | 1.000 |
| 1:165896321:T:C | L163P | 1.000 |
| 1:165903268:T:C | F196L | 1.000 |
| 1:165903270:C:A | F196L | 1.000 |
| 1:165903270:C:G | F196L | 1.000 |
| 1:165905934:C:A | A204D | 1.000 |
| 1:165907696:T:C | L220P | 1.000 |
| 1:165827904:G:A | G24D | 0.999 |
| 1:165827912:G:A | G27R | 0.999 |
| 1:165827912:G:C | G27R | 0.999 |
| 1:165827912:G:T | G27W | 0.999 |
| 1:165827913:G:A | G27E | 0.999 |
| 1:165827915:G:A | G28R | 0.999 |
| 1:165827915:G:C | G28R | 0.999 |
| 1:165827924:A:C | S31R | 0.999 |
| 1:165827926:C:A | S31R | 0.999 |
| 1:165827926:C:G | S31R | 0.999 |
| 1:165827927:G:C | G32R | 0.999 |
| 1:165827928:G:A | G32D | 0.999 |
| 1:165827928:G:T | G32V | 0.999 |
| 1:165890294:T:C | F64L | 0.999 |
| 1:165890296:C:A | F64L | 0.999 |
| 1:165890296:C:G | F64L | 0.999 |
| 1:165890350:C:A | N82K | 0.999 |
| 1:165890350:C:G | N82K | 0.999 |
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):
| Study | Trait | p-value |
|---|---|---|
| GCST002022_12 | Testicular germ cell tumor | 2.000000e-08 |
| GCST002023_7 | Testicular germ cell tumor | 6.000000e-06 |
| GCST002855_4 | Testicular germ cell tumor | 2.000000e-07 |
| GCST004635_3 | Testicular germ cell tumor | 5.000000e-11 |
| GCST004713_14 | Testicular germ cell tumor | 2.000000e-14 |
| GCST009597_237 | Multiple sclerosis | 8.000000e-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).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.00 | Ki | 1000 | nM | CHEMBL1592234 |
| 5.52 | IC50 | 3000 | nM | CHEMBL1592234 |
| 5.46 | Ki | 3500 | nM | CHEMBL1592234 |
| 5.42 | IC50 | 3800 | nM | CHEMBL1592234 |
| 5.33 | IC50 | 4700 | nM | CHEMBL4588628 |
| 5.04 | IC50 | 9200 | nM | CHEMBL4553820 |
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.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 3-[[2-[[9-methyl-2-(4-methylphenyl)-5H-chromeno[2,3-d]pyrimidin-4-yl]sulfanyl]acetyl]amino]benzoic acid | 1589138: 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 assay | ki | 1.0000 | uM |
| 3-[[2-[(9-methyl-2-phenyl-5H-chromeno[2,3-d]pyrimidin-4-yl)sulfanyl]acetyl]amino]benzoic acid | 1589134: 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 | ic50 | 4.7000 | uM |
| N-(4-bromophenyl)-2-[[1-(4-fluorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]acetamide | 1589135: 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 assay | ic50 | 9.2000 | uM |
CTD chemical–gene interactions
52 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | decreases expression, increases expression, affects cotreatment | 4 |
| Estradiol | increases expression | 3 |
| sodium arsenite | decreases expression, increases expression | 2 |
| Fluorouracil | decreases expression, affects response to substance | 2 |
| 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide | decreases expression | 2 |
| Cyclosporine | increases expression | 2 |
| Aflatoxin B1 | increases expression | 2 |
| Cadmium Chloride | decreases expression, increases expression | 2 |
| GSK-J4 | decreases expression | 1 |
| afuresertib | decreases expression | 1 |
| methylmercuric chloride | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| methylselenic acid | decreases expression | 1 |
| trichostatin A | affects expression | 1 |
| cobaltous chloride | decreases expression | 1 |
| benzo(e)pyrene | increases methylation | 1 |
| 2,3-bis(3’-hydroxybenzyl)butyrolactone | affects cotreatment, increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| abrine | decreases expression | 1 |
| 2’-C-methylcytidine | decreases phosphorylation, increases phosphorylation | 1 |
| (+)-JQ1 compound | decreases expression | 1 |
| Resveratrol | affects cotreatment, increases expression | 1 |
| Atrazine | increases expression | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Benzoates | decreases expression | 1 |
| Calcitriol | decreases expression, affects cotreatment | 1 |
| Carbamazepine | affects expression | 1 |
| Coumestrol | affects cotreatment, increases expression | 1 |
ChEMBL screening assays
25 unique, capped per target: 25 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4387679 | Binding | 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 | Discovery 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):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_XU88 | HAP1 UCK2 (-) | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): multiple sclerosis, testicular cancer, testicular germ cell tumor