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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DTYMK
deoxythymidylate kinase
Chromosome 2 Β· 2q37.3
NCBI Gene: 1841Ensembl: ENSG00000168393.14HGNC: HGNC:3061UniProt: P23919
55PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
dTMP kinase activityATP bindingdTDP biosynthetic processthymidine biosynthetic processneurodegeneration, childhood-onset, with progressive microcephalyneurodegenerative diseasemicrocephalySeizure
✦AI Summary

DTYMK (deoxythymidylate kinase) catalyzes the ATP-dependent phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), a critical precursor in the pyrimidine nucleotide biosynthetic pathway essential for DNA synthesis 1. This enzyme functions in both de novo and salvage pathways of thymidylate metabolism, operating in multiple cellular compartments including the cytoplasm, nucleus, and mitochondria. In cancer biology, DTYMK has emerged as a significant oncogenic driver. DTYMK is abnormally upregulated across multiple cancer types and correlates with poor prognosis, advanced tumor stage, and worse overall survival in hepatocellular carcinoma, lung adenocarcinoma, and other malignancies 23. Mechanistically, DTYMK promotes cancer cell proliferation through multiple pathways: it regulates cell cycle progression 3, activates STAT3 signaling 4, and enhances PI3K/AKT pathway activation 1. DTYMK expression correlates with functional hallmarks of malignancy including DNA damage/repair, epithelial-mesenchymal transition, and immune infiltration of B cells, CD4+/CD8+ T cells, macrophages, and dendritic cells 2. Clinically, elevated DTYMK serves as a diagnostic and prognostic biomarker across cancer types. DTYMK inhibitors (YMU1, pamiparib combinations) show therapeutic promise in suppressing lung adenocarcinoma and uveal melanoma progression 45. A known disease association exists with childhood-onset neurodegeneration with progressive microcephaly, though mechanistic details are absent from provided abstracts.

Sources cited
1
DTYMK catalyzes ATP-based conversion of dTMP to dTDP in de novo and salvage pathways; involved in pyrimidine metabolism
PMID: 37358701
2
DTYMK abnormally expressed across cancer types; upregulation predicts poor survival; correlates with cell cycle, DNA damage, DNA repair, and immune infiltration
PMID: 36159971
3
DTYMK upregulated in HCC; high expression correlates with worse overall survival, relapse-free survival, and disease-specific survival; promotes cell proliferation by regulating cell cycle
PMID: 34369850
4
DTYMK knockdown suppresses lung adenocarcinoma progression through repression of STAT3 signaling; YMU1 DTYMK inhibitor shows therapeutic potential
PMID: 36939206
5
Co-targeting DTYMK and PARP1 shows synergistic/additive cytotoxic effects in uveal melanoma; combined inhibition inhibits mTOR signaling and cell migration
PMID: 39195238
6
DTYMK is epigenetically regulated in HCC; p300/CBP-mediated histone acetylation at DTYMK promoter drives nucleotide synthesis; DTYMK overexpression partially reverses p300 inhibitor effects
PMID: 33361394
Disease Associationsβ“˜21
neurodegeneration, childhood-onset, with progressive microcephalyOpen Targets
0.67Moderate
neurodegenerative diseaseOpen Targets
0.55Moderate
microcephalyOpen Targets
0.47Moderate
Global brain atrophyOpen Targets
0.46Moderate
Global developmental delayOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.46Moderate
SeizureOpen Targets
0.46Moderate
uterine fibroidOpen Targets
0.14Weak
HepatomegalyOpen Targets
0.14Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
isolated asymptomatic elevation of creatine phosphokinaseOpen Targets
0.06Suggestive
pancreatic adenocarcinomaOpen Targets
0.05Suggestive
lung cancerOpen Targets
0.04Suggestive
diverticular diseaseOpen Targets
0.04Suggestive
melanomaOpen Targets
0.03Suggestive
Neurodegeneration, childhood-onset, with progressive microcephalyUniProt
Pathogenic Variants5
NM_012145.4(DTYMK):c.265_270del (p.Gln89_Gly90del)Likely pathogenic
Neurodegeneration, childhood-onset, with progressive microcephaly
β˜…β˜†β˜†β˜†2025β†’ Residue 89
NM_012145.4(DTYMK):c.295G>A (p.Ala99Thr)Pathogenic
Neurodegeneration, childhood-onset, with progressive microcephaly
β˜†β˜†β˜†β˜†2022β†’ Residue 99
NM_012145.4(DTYMK):c.242C>T (p.Pro81Leu)Pathogenic
Neurodegeneration, childhood-onset, with progressive microcephaly
β˜†β˜†β˜†β˜†2022β†’ Residue 81
NM_012145.4(DTYMK):c.287_320del (p.Asp96fs)Pathogenic
Neurodegeneration, childhood-onset, with progressive microcephaly
β˜†β˜†β˜†β˜†2022β†’ Residue 96
NM_012145.4(DTYMK):c.382G>A (p.Asp128Asn)Pathogenic
Neurodegeneration, childhood-onset, with progressive microcephaly
β˜†β˜†β˜†β˜†2022β†’ Residue 128
View on ClinVar β†—
Related Genes
NME1Protein interaction99%DGUOKProtein interaction98%NME2Protein interaction97%NME1-NME2Protein interaction96%GARTProtein interaction96%AK2Protein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
50%
Brain
48%
Ovary
34%
Lung
34%
Heart
27%
Gene Interaction Network
Click a node to explore
DTYMKNME1DGUOKNME2NME1-NME2GARTAK2
PROTEIN STRUCTURE
Preparing viewer…
PDB1NN5 Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.40LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.97 [0.68–1.40]
RankingsWhere DTYMK stands among ~20K protein-coding genes
  • #8,196of 20,598
    Most Researched55
  • #3,573of 5,498
    Most Pathogenic Variants5
  • #14,533of 17,882
    Most Constrained (LOEUF)1.40
Genes detectedDTYMK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism.
PMID: 33361394
Cancer Res Β· 2021
1.00
2
Pan-cancer analysis of prognostic and immunological role of DTYMK in human tumors.
PMID: 36159971
Front Genet Β· 2022
0.90
3
The evolving landscape of involvement of DTYMK enzymes in cancer.
PMID: 37358701
Med Oncol Β· 2023
0.80
4
Comprehensive analysis of DTYMK in pan-cancer and verification in lung adenocarcinoma.
PMID: 36094557
Biosci Rep Β· 2022
0.70
5
Knockdown of deoxythymidylate kinase suppresses progression and epithelial-mesenchymal-transition of lung adenocarcinoma via STAT3 signaling.
PMID: 36939206
Physiol Genomics Β· 2023
0.60