Details for: DCTD

Gene ID: 1635

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DCTD

Ensembl ID: ENSG00000129187

Description: dCMP deaminase

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • podocyte CL0000653
    CSI 10.26
    rCSI 45.6%
    PRS 67.54
  • duct epithelial cell CL0000068
    CSI 6.78
    rCSI 9.92%
    PRS 72.22
  • type B pancreatic cell CL0000169
    CSI 5.59
    rCSI 12.37%
    PRS 65.77
  • Kupffer cell CL0000091
    CSI 5.15
    rCSI 11.78%
    PRS 67.85
  • epithelial cell CL0000066
    CSI 4.35
    rCSI 6.69%
    PRS 60.92
  • fibroblast of lung CL0002553
    CSI 3.98
    rCSI 3.7%
    PRS 68.17
  • renal alpha-intercalated cell CL0005011
    CSI 3.28
    rCSI 4.38%
    PRS 75.84
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.27
    rCSI 2.34%
    PRS 81.36
  • double negative thymocyte CL0002489
    CSI 3.21
    rCSI 2.23%
    PRS 78.93
  • unswitched memory B cell CL0000970
    CSI 3.2
    rCSI 2.69%
    PRS 83.28
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.15
    rCSI 2.2%
    PRS 70.38
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.15
    rCSI 2.4%
    PRS 80.56
  • hepatocyte CL0000182
    CSI 2.93
    rCSI 5.24%
    PRS 66.91
  • myofibroblast cell CL0000186
    CSI 2.88
    rCSI 3.99%
    PRS 67.28
  • mature B cell CL0000785
    CSI 2.8
    rCSI 2.43%
    PRS 78.07
  • multi-ciliated epithelial cell CL0005012
    CSI 2.78
    rCSI 2.78%
    PRS 60.89
  • vascular associated smooth muscle cell CL0000359
    CSI 2.72
    rCSI 8.81%
    PRS 66.9
  • naive T cell CL0000898
    CSI 2.66
    rCSI 1.85%
    PRS 82.53
  • common myeloid progenitor CL0000049
    CSI 2.61
    rCSI 2.11%
    PRS 69.26
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.6
    rCSI 2.56%
    PRS 82.76
  • tracheobronchial serous cell CL0019001
    CSI 2.58
    rCSI 11.17%
    PRS 78.58
  • perivascular cell CL4033054
    CSI 2.58
    rCSI 3.52%
    PRS 73.26
  • CD4-positive helper T cell CL0000492
    CSI 2.53
    rCSI 1.92%
    PRS 80.9
  • interstitial cell of Cajal CL0002088
    CSI 2.52
    rCSI 3.2%
    PRS 73.61
  • ionocyte CL0005006
    CSI 2.5
    rCSI 2.67%
    PRS 67.61
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 2.45
    rCSI 1.45%
    PRS 84.43
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.38
    rCSI 2.15%
    PRS 64.6
  • skin fibroblast CL0002620
    CSI 2.32
    rCSI 2%
    PRS 71.59
  • mucous neck cell CL0000651
    CSI 2.17
    rCSI 3.13%
    PRS 76.98
  • alveolar adventitial fibroblast CL4028006
    CSI 2.17
    rCSI 3.43%
    PRS 69.93
  • bronchus fibroblast of lung CL2000093
    CSI 2.16
    rCSI 1.75%
    PRS 67.88
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.15
    rCSI 1.66%
    PRS 70.41
  • cerebral cortex endothelial cell CL1001602
    CSI 2.14
    rCSI 3.7%
    PRS 57.83
  • intestine goblet cell CL0019031
    CSI 2.12
    rCSI 1.89%
    PRS 65.17
  • immature B cell CL0000816
    CSI 2.12
    rCSI 1.57%
    PRS 80.5
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.1
    rCSI 1.42%
    PRS 80.97
  • activated type II NK T cell CL0000931
    CSI 2.1
    rCSI 2.37%
    PRS 83.46
  • plasmablast CL0000980
    CSI 2.09
    rCSI 1.65%
    PRS 73.97
  • club cell CL0000158
    CSI 2.08
    rCSI 3.04%
    PRS 62.57
  • intestinal epithelial cell CL0002563
    CSI 2.06
    rCSI 2.15%
    PRS 65.3
  • myeloid leukocyte CL0000766
    CSI 2.05
    rCSI 1.89%
    PRS 69.28
  • vascular leptomeningeal cell CL4023051
    CSI 2.05
    rCSI 3.6%
    PRS 59.9
  • stem cell CL0000034
    CSI 2.02
    rCSI 1.95%
    PRS 58.76
  • acinar cell CL0000622
    CSI 1.99
    rCSI 2.92%
    PRS 78.63
  • pro-B cell CL0000826
    CSI 1.98
    rCSI 1.64%
    PRS 69.83
  • neural crest cell CL0011012
    CSI 1.97
    rCSI 1.56%
    PRS 54.53
  • epithelial cell of lung CL0000082
    CSI 1.96
    rCSI 1.63%
    PRS 67.13
  • lung neuroendocrine cell CL1000223
    CSI 1.93
    rCSI 2.86%
    PRS 72.65
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.93
    rCSI 2.4%
    PRS 46.79
  • group 3 innate lymphoid cell CL0001071
    CSI 1.93
    rCSI 1.45%
    PRS 73.28
  • granulocyte CL0000094
    CSI 1.92
    rCSI 2.94%
    PRS 76.58
  • hematopoietic stem cell CL0000037
    CSI 1.88
    rCSI 1.25%
    PRS 70.39
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 1.87
    rCSI 2.65%
    PRS 63.81
  • colon epithelial cell CL0011108
    CSI 1.87
    rCSI 1.96%
    PRS 64.1
  • early lymphoid progenitor CL0000936
    CSI 1.81
    rCSI 1.59%
    PRS 72.85
  • enteric smooth muscle cell CL0002504
    CSI 1.79
    rCSI 2.56%
    PRS 69.39
  • foveolar cell of stomach CL0002179
    CSI 1.78
    rCSI 3.78%
    PRS 77.01
  • rod bipolar cell CL0000751
    CSI 1.76
    rCSI 3.16%
    PRS 60.56
  • extravillous trophoblast CL0008036
    CSI 1.73
    rCSI 2.14%
    PRS 64.3
  • respiratory suprabasal cell CL4033048
    CSI 1.72
    rCSI 2.2%
    PRS 71.92
  • myoepithelial cell CL0000185
    CSI 1.66
    rCSI 4.2%
    PRS 74.85
  • choroid plexus epithelial cell CL0000706
    CSI 1.63
    rCSI 2.67%
    PRS 56.54
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.63
    rCSI 2.1%
    PRS 50.06
  • pancreatic acinar cell CL0002064
    CSI 1.57
    rCSI 2.09%
    PRS 73.7
  • ciliated epithelial cell CL0000067
    CSI 1.56
    rCSI 1.37%
    PRS 55.34
  • transit amplifying cell of colon CL0009011
    CSI 1.55
    rCSI 1.82%
    PRS 69.45
  • radial glial cell CL0000681
    CSI 1.51
    rCSI 2.1%
    PRS 66.11
  • dendritic cell, human CL0001056
    CSI 1.49
    rCSI 2.29%
    PRS 76.79
  • intermediate monocyte CL0002393
    CSI 1.48
    rCSI 2.23%
    PRS 72.38
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.48
    rCSI 2.48%
    PRS 48.74
  • peripheral nervous system neuron CL2000032
    CSI 1.48
    rCSI 2.01%
    PRS 58.94
  • common lymphoid progenitor CL0000051
    CSI 1.47
    rCSI 1.97%
    PRS 86.24
  • chondrocyte CL0000138
    CSI 1.42
    rCSI 2.26%
    PRS 60.12
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.39
    rCSI 1.67%
    PRS 48.56
  • erythroid progenitor cell CL0000038
    CSI 1.38
    rCSI 7.93%
    PRS 75.52
  • mesodermal cell CL0000222
    CSI 1.36
    rCSI 1.63%
    PRS 65.63
  • lung ciliated cell CL1000271
    CSI 1.31
    rCSI 1.52%
    PRS 58.13
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.25
    rCSI 2.79%
    PRS 49.37
  • placental villous trophoblast CL2000060
    CSI 1.24
    rCSI 1.92%
    PRS 65.97
  • enteroendocrine cell CL0000164
    CSI 1.24
    rCSI 1.69%
    PRS 68.48
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.13
    rCSI 2%
    PRS 47.81
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.12
    rCSI 0.86%
    PRS 68.82
  • retinal cone cell CL0000573
    CSI 1.11
    rCSI 1.78%
    PRS 56.92
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.07
    rCSI 0.93%
    PRS 72.28
  • lung macrophage CL1001603
    CSI 1.06
    rCSI 2.38%
    PRS 75.17
  • pancreatic PP cell CL0002275
    CSI 1.06
    rCSI 4.2%
    PRS 78.18
  • pancreatic ductal cell CL0002079
    CSI 1.05
    rCSI 2.04%
    PRS 70.52
  • alternatively activated macrophage CL0000890
    CSI 1.05
    rCSI 1.32%
    PRS 78.9
  • mesenchymal cell CL0008019
    CSI 0.98
    rCSI 2.48%
    PRS 61.31
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.95
    rCSI 4.74%
    PRS 80.07
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.74
    rCSI 1.81%
    PRS 47.11
  • endothelial cell of placenta CL0009092
    CSI 0.71
    rCSI 3.48%
    PRS 78.03
  • pancreatic stellate cell CL0002410
    CSI 0.5
    rCSI 2.91%
    PRS 75.06
  • bronchial goblet cell CL1000312
    CSI 0.41
    rCSI 1.65%
    PRS 80.82

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [DCTD](/details-gene/1635) encodes dCMP deaminase, a key cytoplasmic enzyme in the pyrimidine nucleotide metabolic pathway. Its primary function is to catalyze the deamination of deoxycytidylate (dCMP) to deoxyuridylate (dUMP), a crucial step in the *de novo* synthesis of thymidylate (dTMP), an essential precursor for DNA replication and repair. Reflecting this fundamental role, [DCTD](/details-gene/1635) shows significant expression across a range of metabolically active and specialized cell types. **Overall**, it exhibits particularly high significance in [podocytes](/details-cell/CL0000653), various [epithelial cells](/details-cell/CL0000066), and endocrine cells like [type B pancreatic cells](/details-cell/CL0000169), suggesting a role beyond simple cell proliferation in maintaining cellular homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [DCTD](/details-gene/1635) indicates its importance in a diverse set of tissues and cell lineages, consistent with its central role in nucleotide metabolism. **Overall**, the gene's significance is most pronounced in highly specialized, metabolically active cells. The highest significance score is observed in [podocytes](/details-cell/CL0000653) (CSI: 10.26), which are terminally differentiated cells in the kidney glomerulus, suggesting a critical, non-proliferative function. High significance is also noted in various epithelial and secretory cells, including [duct epithelial cells](/details-cell/CL0000068) and [type B pancreatic cells](/details-cell/CL0000169). Furthermore, [DCTD](/details-gene/1635) is significantly expressed in liver cell types, including [Kupffer cells](/details-cell/CL0000091) and [hepatocytes](/details-cell/CL0000182), as well as structural cells like [fibroblasts of lung](/details-cell/CL0002553). Its notable presence in multiple lymphocyte populations, such as [CD4-positive, alpha-beta memory T cells](/details-cell/CL0000897) and [effector CD8-positive, alpha-beta T cells](/details-cell/CL0001050), is consistent with the high demand for DNA precursors during immune cell activation and clonal expansion. ## Pathways and Molecular Function Functionally, [DCTD](/details-gene/1635) is integral to nucleotide biosynthesis. Its molecular function is defined as [dCMP deaminase activity](/details-go/GO:0004132) [Link](https://doi.org/10.1016/s0021-9258(18)31483-2). This activity is a central node in the [pyrimidine nucleotide metabolic process](/details-go/GO:0006220), which is part of the broader [nucleoside salvage](/details-go/GO:0043174) and [nucleotide biosynthetic process](/details-go/GO:0009165) pathways. According to Reactome, this function contributes to the [Metabolism of nucleotides](/details-pathway/R-HSA-15869). The protein product is localized to the [cytoplasm](/details-go/GO:0005737) and [cytosol](/details-go/GO:0005829), where it performs its catalytic function. It also exhibits [zinc ion binding](/details-go/GO:0008270) capability, which is often essential for enzymatic stability and activity. The gene's role in supplying dTMP precursors directly supports DNA replication, a process vital for the highly proliferative immune cells and metabolically active tissues where its expression is prominent. ## Research Directions Given that dCMP deaminase is a rate-limiting enzyme in dTMP synthesis, its regulation and context-specific roles warrant further investigation, particularly in disease states characterized by altered metabolism or proliferation. ### Proposed Hypotheses 1. **Role in Cancer Synthetic Lethality:** The over-reliance of some cancer cells on specific metabolic pathways presents therapeutic opportunities. It is hypothesized that rapidly proliferating tumors, particularly those with deficiencies in other DNA repair pathways (e.g., BRCA1/2 mutations), may exhibit heightened dependence on the [DCTD](/details-gene/1635)-mediated salvage pathway for dTMP synthesis. Inhibition of [DCTD](/details-gene/1635) could therefore induce synthetic lethality, potentially sensitizing these tumors to agents like PARP inhibitors, a concept demonstrated for other nucleotide salvage factors [Link](https://doi.org/10.1126/science.abb4542). 2. **Non-Canonical Role in Podocyte Homeostasis:** The remarkably high significance of [DCTD](/details-gene/1635) in terminally differentiated [podocytes](/details-cell/CL0000653) is unexpected for an enzyme primarily linked to nuclear DNA replication. We hypothesize that in [podocytes](/details-cell/CL0000653), [DCTD](/details-gene/1635) is critical for maintaining mitochondrial DNA (mtDNA) integrity. These cells have high energy demands and are vulnerable to mitochondrial dysfunction; a stable supply of dNTPs from [DCTD](/details-gene/1635) may be essential for the constant repair of oxidatively damaged mtDNA, thereby preserving podocyte function and glomerular filtration barrier integrity. ### Key Experimental Approach To test the hypothesis regarding the role of [DCTD](/details-gene/1635) in [podocyte](/details-cell/CL0000653) homeostasis (Hypothesis 2), a conditional knockout mouse model could be generated using the Cre-Lox system with a podocyte-specific driver (e.g., *Nphs2*-Cre). The resulting *Dctd* knockout mice would be examined for renal phenotypes under both baseline and stressed conditions, such as induction of diabetic nephropathy. Key experimental readouts would include transmission electron microscopy to assess podocyte foot process architecture, albumin-to-creatinine ratio measurements to quantify proteinuria, and molecular assays on isolated glomeruli to measure mtDNA copy number, lesion frequency, and mitochondrial respiratory function. ### Therapeutic Potential As an enzyme central to DNA synthesis, [DCTD](/details-gene/1635) represents a plausible therapeutic target, primarily for **inhibition**. Its role in supplying nucleotide precursors makes it an attractive target in oncology, where uncontrolled proliferation is a hallmark. The development of specific small molecule inhibitors against [DCTD](/details-gene/1635) could offer a strategy to starve cancer cells of essential DNA building blocks. However, given its expression in various healthy tissues, systemic toxicity could be a concern. A precision medicine approach, such as targeting cancers with specific genetic vulnerabilities that create a dependency on the [DCTD](/details-gene/1635) pathway, may be required to achieve a favorable therapeutic window.

Genular Protein ID: 729643614

Symbol: DCTD_HUMAN

Name: N/A

UniProtKB Accession Codes:

P32321 B2R836 D3DP49 D3DP50 Q5M7Z8 Q9BVD8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 14 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 10 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 2 PIRSF 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 12 Rhea 4 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7685356

Title: Primary structure of human deoxycytidylate deaminase and overexpression of its functional protein in Escherichia coli.

PubMed ID: 7685356

DOI: 10.1016/s0021-9258(18)31483-2

PubMed ID: 7642519

Title: Chromosomal location and structural organization of the human deoxycytidylate deaminase gene.

PubMed ID: 7642519

DOI: 10.1074/jbc.270.32.18727

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 33833118

Title: Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors.

PubMed ID: 33833118

DOI: 10.1126/science.abb4542

Sequence Information:

  • Length: 178
  • Mass: 20016
  • Checksum: 2B8DA5EAC85F3666
  • Sequence:
    • MSEVSCKKRD DYLEWPEYFM AVAFLSAQRS KDPNSQVGAC IVNSENKIVG IGYNGMPNGC 
SDDVLPWRRT AENKLDTKYP YVCHAELNAI MNKNSTDVKG CSMYVALFPC NECAKLIIQA 
GIKEVIFMSD KYHDSDEATA ARLLFNMAGV TFRKFIPKCS KIVIDFDSIN SRPSQKLQ