Details for: DNASE2

Gene ID: 1777

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: DNASE2

Ensembl ID: ENSG00000105612

Description: deoxyribonuclease 2, lysosomal

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mononuclear phagocyte CL0000113
    CSI 13
    rCSI 28.62%
    PRS 81.24
  • pancreatic acinar cell CL0002064
    CSI 10.88
    rCSI 14.46%
    PRS 83.12
  • mesodermal cell CL0000222
    CSI 9.06
    rCSI 10.87%
    PRS 75.07
  • hematopoietic stem cell CL0000037
    CSI 8.62
    rCSI 5.73%
    PRS 80.24
  • lung neuroendocrine cell CL1000223
    CSI 7.05
    rCSI 10.42%
    PRS 81.84
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 6.35
    rCSI 8.65%
    PRS 93.84
  • M cell of gut CL0000682
    CSI 5.57
    rCSI 5.92%
    PRS 82.85
  • non-classical monocyte CL0000875
    CSI 4.81
    rCSI 7.71%
    PRS 89.32
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.37
    rCSI 3.32%
    PRS 89.42
  • activated type II NK T cell CL0000931
    CSI 4.03
    rCSI 4.53%
    PRS 90.24
  • lung interstitial macrophage CL4033043
    CSI 3.96
    rCSI 8.9%
    PRS 89.92
  • elicited macrophage CL0000861
    CSI 3.63
    rCSI 3.33%
    PRS 85.36
  • epithelial cell of lung CL0000082
    CSI 3.54
    rCSI 2.94%
    PRS 77.94
  • mucus secreting cell CL0000319
    CSI 3.34
    rCSI 5.3%
    PRS 86.5
  • dendritic cell, human CL0001056
    CSI 3.22
    rCSI 4.94%
    PRS 85.87
  • interstitial cell of Cajal CL0002088
    CSI 3.11
    rCSI 3.95%
    PRS 82.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.93
    rCSI 2.92%
    PRS 71.04
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.88
    rCSI 8.33%
    PRS 77.06
  • pancreatic D cell CL0000173
    CSI 2.8
    rCSI 2.75%
    PRS 80.28
  • T-helper 17 cell CL0000899
    CSI 2.7
    rCSI 2.15%
    PRS 93.49
  • ciliated cell CL0000064
    CSI 2.68
    rCSI 4.34%
    PRS 72.59
  • intermediate monocyte CL0002393
    CSI 2.64
    rCSI 3.98%
    PRS 82.72
  • pancreatic PP cell CL0002275
    CSI 2.63
    rCSI 10.47%
    PRS 85.64
  • duct epithelial cell CL0000068
    CSI 2.61
    rCSI 3.82%
    PRS 82.21
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 2.61
    rCSI 3.58%
    PRS 92.63
  • secretory cell CL0000151
    CSI 2.53
    rCSI 2.64%
    PRS 76.71
  • pancreatic A cell CL0000171
    CSI 2.36
    rCSI 2.47%
    PRS 80.85
  • extravillous trophoblast CL0008036
    CSI 2.3
    rCSI 2.84%
    PRS 75.07
  • ciliated epithelial cell CL0000067
    CSI 2.24
    rCSI 1.97%
    PRS 66.21
  • enteric smooth muscle cell CL0002504
    CSI 2.24
    rCSI 3.19%
    PRS 78.33
  • plasmablast CL0000980
    CSI 2.14
    rCSI 1.69%
    PRS 82.92
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.11
    rCSI 2.07%
    PRS 90.82
  • pulmonary ionocyte CL0017000
    CSI 2.09
    rCSI 2.55%
    PRS 83.95
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.08
    rCSI 2.72%
    PRS 88.1
  • skin fibroblast CL0002620
    CSI 2.07
    rCSI 1.79%
    PRS 78.77
  • respiratory basal cell CL0002633
    CSI 2.05
    rCSI 2.13%
    PRS 81.87
  • myofibroblast cell CL0000186
    CSI 2.05
    rCSI 2.84%
    PRS 74.95
  • Langerhans cell CL0000453
    CSI 2.02
    rCSI 3.08%
    PRS 88.71
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.01
    rCSI 2.04%
    PRS 87.48
  • pulmonary artery endothelial cell CL1001568
    CSI 2
    rCSI 2.72%
    PRS 86.25
  • alveolar type 1 fibroblast cell CL4028004
    CSI 1.98
    rCSI 2.17%
    PRS 79.55
  • group 3 innate lymphoid cell CL0001071
    CSI 1.95
    rCSI 1.47%
    PRS 83.23
  • monocyte CL0000576
    CSI 1.93
    rCSI 3.5%
    PRS 83.55
  • inflammatory macrophage CL0000863
    CSI 1.92
    rCSI 3.27%
    PRS 92.76
  • myeloid leukocyte CL0000766
    CSI 1.85
    rCSI 1.71%
    PRS 78.9
  • alveolar macrophage CL0000583
    CSI 1.8
    rCSI 2.96%
    PRS 81.66
  • bronchus fibroblast of lung CL2000093
    CSI 1.77
    rCSI 1.44%
    PRS 76.76
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.75
    rCSI 1.35%
    PRS 79.98
  • placental villous trophoblast CL2000060
    CSI 1.73
    rCSI 2.68%
    PRS 76.36
  • BEST4+ enteroycte CL4030026
    CSI 1.71
    rCSI 2.13%
    PRS 78.72
  • alveolar adventitial fibroblast CL4028006
    CSI 1.71
    rCSI 2.7%
    PRS 79.06
  • macrophage CL0000235
    CSI 1.67
    rCSI 3.04%
    PRS 85.65
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.65
    rCSI 2.12%
    PRS 73.6
  • alternatively activated macrophage CL0000890
    CSI 1.58
    rCSI 1.98%
    PRS 86.84
  • forebrain radial glial cell CL0013000
    CSI 1.54
    rCSI 4.94%
    PRS 79.76
  • glioblast CL0000030
    CSI 1.53
    rCSI 2.44%
    PRS 69.04
  • stem cell CL0000034
    CSI 1.52
    rCSI 1.46%
    PRS 70.25
  • acinar cell CL0000622
    CSI 1.51
    rCSI 2.21%
    PRS 86.95
  • ionocyte CL0005006
    CSI 1.5
    rCSI 1.61%
    PRS 78.36
  • club cell CL0000158
    CSI 1.46
    rCSI 2.14%
    PRS 71.87
  • lung ciliated cell CL1000271
    CSI 1.45
    rCSI 1.68%
    PRS 69.22
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.44
    rCSI 1.38%
    PRS 76.59
  • enteroendocrine cell CL0000164
    CSI 1.4
    rCSI 1.92%
    PRS 77.71
  • radial glial cell CL0000681
    CSI 1.23
    rCSI 1.71%
    PRS 76.07
  • retina horizontal cell CL0000745
    CSI 1.21
    rCSI 1.84%
    PRS 74.12
  • pancreatic ductal cell CL0002079
    CSI 1.18
    rCSI 2.29%
    PRS 80.56
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.16
    rCSI 1.4%
    PRS 85.19
  • lung macrophage CL1001603
    CSI 0.99
    rCSI 2.22%
    PRS 84.65
  • mesenchymal cell CL0008019
    CSI 0.97
    rCSI 2.46%
    PRS 70.66
  • pancreatic stellate cell CL0002410
    CSI 0.94
    rCSI 5.45%
    PRS 81.73
  • type B pancreatic cell CL0000169
    CSI 0.88
    rCSI 1.95%
    PRS 76.66
  • pancreatic epsilon cell CL0005019
    CSI 0.79
    rCSI 3.67%
    PRS 87.1
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 0.7
    rCSI 7.61%
    PRS 88.61
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.53
    rCSI 2.65%
    PRS 88.86
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.3
    rCSI 1.64%
    PRS 86.44

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.

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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 [DNASE2](/details-gene/1777), or Deoxyribonuclease II, is a protein-coding gene located on chromosome 19p13.13. It encodes a lysosomal endonuclease that functions in a pH-optimum acidic environment to hydrolyze DNA. The primary function of [DNASE2](/details-gene/1777) is the degradation of DNA from apoptotic cells and cellular debris, a critical process for maintaining tissue homeostasis and preventing autoimmune responses to self-DNA. Expression data indicates that [DNASE2](/details-gene/1777) is a gene of high significance in phagocytic cells, particularly [mononuclear phagocytes](/details-cell/CL0000113), as well as in certain highly active secretory cells like [pancreatic acinar cells](/details-cell/CL0002064). Its function is clinically relevant and associated with an OMIM entry ([126350](https://omim.org/entry/126350)). ## Cellular Roles and Expression Landscape The expression profile of [DNASE2](/details-gene/1777) highlights its central role in cells responsible for waste clearance, tissue remodeling, and immune surveillance. **Overall**, the gene shows its highest significance in the [mononuclear phagocyte](/details-cell/CL0000113) system (CSI: 13.00), which includes cell types such as [non-classical monocytes](/details-cell/CL0000875), [lung interstitial macrophages](/details-cell/CL4033043), and [dendritic cells](/details-cell/CL0001056). This expression pattern is highly consistent with its canonical function in degrading DNA from engulfed apoptotic bodies within the lysosome. Beyond professional phagocytes, [DNASE2](/details-gene/1777) is also a significant gene in [pancreatic acinar cells](/details-cell/CL0002064) (CSI: 10.88), suggesting a role in cellular quality control or autophagy within these highly secretory cells. Furthermore, its expression in [hematopoietic stem cells](/details-cell/CL0000037) (CSI: 8.62) and various adaptive immune cells, such as [effector memory CD4-positive, alpha-beta T cells](/details-cell/CL0000905) and [effector CD8-positive, alpha-beta T cells](/details-cell/CL0001050), may indicate its involvement in immune cell development, turnover, and the regulation of immune responses. The gene's broad but specific expression pattern points to a fundamental housekeeping role, particularly in cells with high rates of phagocytosis, secretion, or differentiation. The absence of high significance in cell types like neurons or structural fibroblasts suggests a specialized function primarily within hematopoietic, immune, and certain epithelial lineages. ## Pathways and Molecular Function The functional annotations for [DNASE2](/details-gene/1777) align closely with its observed cellular expression pattern. Its molecular function is defined as [deoxyribonuclease II activity](/details-go/GO:0004531), operating within the [lysosome](/details-go/GO:0005764). This enzymatic activity is integral to the biological process of [apoptotic DNA fragmentation](/details-go/GO:0006309), which is essential for safely recycling nucleic acids from dead cells. This function directly supports its high significance in phagocytes, which are responsible for clearing such material from tissues. Furthermore, its involvement in [enucleate erythrocyte differentiation](/details-go/GO:0043353) is consistent with its expression in [hematopoietic stem cells](/details-cell/CL0000037), as it is required for the degradation of the extruded nucleus during erythropoiesis. The gene is also annotated to the [regulation of immune response](/details-go/GO:0050776), underscoring that the proper disposal of self-DNA is a critical checkpoint to prevent the activation of innate immune sensors and subsequent autoimmunity. Reactome pathway analysis highlights its dependence on vesicle-mediated transport machinery, including [lysosome vesicle biogenesis](/details-pathway/R-HSA-432720) and [trans-Golgi network vesicle budding](/details-pathway/R-HSA-199992), which are necessary to deliver the enzyme to its site of action in the lysosome. Early cloning and characterization studies confirmed its potential role in apoptosis ([Link](https://doi.org/10.1074/jbc.273.47.30909)). ## Research Directions The well-defined role of [DNASE2](/details-gene/1777) in DNA degradation within phagocytes provides a strong foundation for investigating its role in pathology, particularly in autoimmune and inflammatory diseases where clearance of cellular debris is impaired. Based on the available data, several testable hypotheses can be proposed: 1. Deficiency or reduced activity of [DNASE2](/details-gene/1777) in macrophages leads to the accumulation of undigested DNA in lysosomal compartments, resulting in lysosomal rupture and the activation of cytosolic DNA sensors (e.g., cGAS-STING), thereby triggering a type I interferon-mediated autoinflammatory response. 2. In [pancreatic acinar cells](/details-cell/CL0002064), [DNASE2](/details-gene/1777) is crucial for managing cellular stress by degrading DNA released during organelle turnover (mitophagy, crinophagy). Its dysfunction may contribute to the inflammatory cascade seen in acute pancreatitis by allowing cytosolic accumulation of mitochondrial or nuclear DNA. A key experiment to test the first hypothesis could involve the following: * **Experimental Approach:** Utilize CRISPR-Cas9 to knock out [DNASE2](/details-gene/1777) in a human monocytic cell line (e.g., THP-1). Differentiate these knockout and wild-type control cells into macrophages and then expose them to apoptotic bodies derived from a separate cell line. The primary readout would be the quantification of type I interferon (IFN-β) and other pro-inflammatory cytokines (e.g., IL-6, TNF-α) in the supernatant via ELISA and their corresponding mRNA levels by RT-qPCR. A significant increase in these markers in the knockout macrophages would support the hypothesis that [DNASE2](/details-gene/1777) is critical for preventing inflammatory responses to apoptotic cell-derived DNA. **Therapeutic Potential:** Given that loss-of-function mutations in [DNASE2](/details-gene/1777) are associated with inflammatory and autoimmune disorders, the therapeutic strategy would focus on **restoration or enhancement** of its function rather than inhibition. As an intracellular lysosomal enzyme, it is not a conventional drug target for small molecule inhibitors or antibodies. Instead, it represents a potential candidate for enzyme replacement therapy (ERT) or gene therapy, particularly for monogenic diseases caused by [DNASE2](/details-gene/1777) deficiency. Such an approach would aim to deliver a functional version of the enzyme to the affected phagocytic cells to restore their capacity for DNA degradation and resolve the underlying inflammation.

Genular Protein ID: 3998119851

Symbol: DNS2A_HUMAN

Name: Deoxyribonuclease-2-alpha

UniProtKB Accession Codes:

O00115 B2RD06 B7Z4K6 O43910

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 13 Ensembl 2 ExpressionAtlas 1 GO 8 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 2 PRO 1 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 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9924608

Title: Structure and organization of the human deoxyribonuclease II (DNase II) gene.

PubMed ID: 9924608

DOI: 10.1046/j.1469-1809.1998.6240299.x

PubMed ID: 9647784

Title: Cloning of cDNAs encoding porcine and human DNase II.

PubMed ID: 9647784

DOI: 10.1006/bbrc.1998.8839

PubMed ID: 9714827

Title: Molecular cloning and characterization of human and murine DNase II.

PubMed ID: 9714827

DOI: 10.1016/s0378-1119(98)00280-7

PubMed ID: 9812984

Title: The cloning and expression of human deoxyribonuclease II. A possible role in apoptosis.

PubMed ID: 9812984

DOI: 10.1074/jbc.273.47.30909

PubMed ID: 9446563

Title: Molecular cloning of the cDNA encoding human deoxyribonuclease II.

PubMed ID: 9446563

DOI: 10.1074/jbc.273.5.2610

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 11906178

Title: Revised structure of the active form of human deoxyribonuclease IIalpha.

PubMed ID: 11906178

DOI: 10.1006/bbrc.2002.6687

PubMed ID: 12558498

Title: Structural requirements of human DNase II alpha for formation of the active enzyme: the role of the signal peptide, N-glycosylation, and disulphide bridging.

PubMed ID: 12558498

DOI: 10.1042/bj20021875

PubMed ID: 12594037

Title: A family history of deoxyribonuclease II: surprises from Trichinella spiralis and Burkholderia pseudomallei.

PubMed ID: 12594037

DOI: 10.1016/s0378-1119(02)01233-7

PubMed ID: 12754519

Title: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.

PubMed ID: 12754519

DOI: 10.1038/nbt827

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

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: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 29259162

Title: Type I interferon-mediated autoinflammation due to DNase II deficiency.

PubMed ID: 29259162

DOI: 10.1038/s41467-017-01932-3

PubMed ID: 31775019

Title: Janus kinase inhibition for autoinflammation in patients with DNASE2 deficiency.

PubMed ID: 31775019

DOI: 10.1016/j.jaci.2019.11.020

Sequence Information:

  • Length: 360
  • Mass: 39581
  • Checksum: DF1BBFBA8A9676EA
  • Sequence:
    • MIPLLLAALL CVPAGALTCY GDSGQPVDWF VVYKLPALRG SGEAAQRGLQ YKYLDESSGG 
WRDGRALINS PEGAVGRSLQ PLYRSNTSQL AFLLYNDQPP QPSKAQDSSM RGHTKGVLLL 
DHDGGFWLVH SVPNFPPPAS SAAYSWPHSA CTYGQTLLCV SFPFAQFSKM GKQLTYTYPW 
VYNYQLEGIF AQEFPDLENV VKGHHVSQEP WNSSITLTSQ AGAVFQSFAK FSKFGDDLYS 
GWLAAALGTN LQVQFWHKTV GILPSNCSDI WQVLNVNQIA FPGPAGPSFN STEDHSKWCV 
SPKGPWTCVG DMNRNQGEEQ RGGGTLCAQL PALWKAFQPL VKNYQPCNGM ARKPSRAYKI