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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DNASE1
deoxyribonuclease 1
Chromosome 16 · 16p13.3
NCBI Gene: 1773Ensembl: ENSG00000213918.11HGNC: HGNC:2956UniProt: P24855
98PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeprotein bindingDNA bindingdeoxyribonuclease I activitysystemic lupus erythematosusAutosomal recessive systemic lupus erythematosustype 2 diabetes mellituscongenital hydronephrosis
✦AI Summary

DNASE1 is a serum endocuclease secreted by exocrine and endocrine organs that plays critical roles in DNA catabolism and inflammation regulation 1. The enzyme preferentially cleaves protein-free DNA and is involved in apoptotic cell death processes 1. A primary function of DNASE1 is degrading neutrophil extracellular traps (NETs)—web-like structures composed of DNA fibers released by neutrophils during inflammation. Together with DNASE1L3, DNASE1 degrades intravascular NETs to prevent pathological thrombosis and organ damage 23. DNASE1 also binds G-actin and inhibits actin polymerization. Dysregulation of DNASE1 activity contributes to multiple disease states. Impaired NET clearance due to reduced DNASE1 function exacerbates atherosclerosis progression by promoting macrophage efferocytosis defects 4. DNASE1 treatment substantially attenuates acetaminophen-induced acute liver injury by reducing NET-mediated hepatocyte PANoptosis 5. Similarly, DNase1 administration diminishes myocardial ischemia-reperfusion injury and fibrotic vascular occlusions in chr16 thrombosis 32. Abnormal plasma nuclease activity, including altered DNASE1 levels, is associated with systemic lupus erythematosus and affects cell-free DNA fragmentation patterns 6. These findings establish DNASE1 as a key therapeutic target across multiple inflammatory and thrombotic conditions.

Sources cited
1
DNASE1 is a serum endocuclease secreted by exocrine organs, involved in apoptosis and cell death processes
PMID: 11241278
2
DNASE1 degrades NETs and DNase1 targeting diminishes fibrosis and promotes thrombus resolution in chronic thrombosis
PMID: 33512471
3
DNase1 treatment substantially attenuates myocardial reperfusion injury by reducing NET-mediated damage
PMID: 38666340
4
Macrophage DNase1 secretion is impaired by endoplasmic reticulum stress in atherosclerosis, leading to NET accumulation and plaque progression
PMID: 41031413
5
DNase1 preinjection inhibits NET formation and alleviates acetaminophen-induced acute liver injury with reduced PANoptosis
PMID: 38589685
6
Plasma nuclease activity including DNASE1 is linked to systemic lupus erythematosus and affects cell-free DNA fragmentation
PMID: 34006390
Disease Associationsⓘ21
systemic lupus erythematosusOpen Targets
0.47Moderate
Autosomal recessive systemic lupus erythematosusOpen Targets
0.39Weak
type 2 diabetes mellitusOpen Targets
0.35Weak
congenital hydronephrosisOpen Targets
0.34Weak
congenital anomalies of kidney and urinary tract 1Open Targets
0.33Weak
congenital anomaly of kidney and urinary tractOpen Targets
0.33Weak
acute tonsillitisOpen Targets
0.32Weak
atrial fibrillationOpen Targets
0.30Weak
neurodegenerative diseaseOpen Targets
0.21Weak
HER2 Positive Breast CarcinomaOpen Targets
0.12Weak
VACTERL/vater associationOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
hereditary renal cell carcinomaOpen Targets
0.11Weak
lupus nephritisOpen Targets
0.10Weak
cancerOpen Targets
0.08Suggestive
autosomal systemic lupus erythematosus type 16Open Targets
0.08Suggestive
subarachnoid hemorrhageOpen Targets
0.08Suggestive
C1Q deficiency 1Open Targets
0.08Suggestive
ganglioneuromaOpen Targets
0.07Suggestive
autoimmune diseaseOpen Targets
0.07Suggestive
Systemic lupus erythematosusUniProt
Pathogenic Variants1
NM_005223.4(DNASE1):c.91C>T (p.Gln31Ter)Likely pathogenic
Systemic lupus erythematosus
★☆☆☆2024→ Residue 31
View on ClinVar ↗
Related Genes
DNASE2Protein interaction60%DNASE1L3Shared pathway38%DNASE1L1Shared pathway33%DNASE1L2Shared pathway33%NME8Shared pathway25%TREX2Shared pathway25%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
84%
Liver
76%
Lung
63%
Heart
49%
Brain
28%
Gene Interaction Network
Click a node to explore
DNASE1DNASE2DNASE1L3DNASE1L1DNASE1L2NME8TREX2
PROTEIN STRUCTURE
Preparing viewer…
PDB4AWN · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.46LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.13 [0.88–1.46]
RankingsWhere DNASE1 stands among ~20K protein-coding genes
  • #4,875of 20,598
    Most Researched98 · top quartile
  • #4,892of 5,498
    Most Pathogenic Variants1
  • #14,930of 17,882
    Most Constrained (LOEUF)1.46
Genes detectedDNASE1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Nexus of cfDNA and Nuclease Biology.
PMID: 34006390
Trends Genet · 2021
1.00
2
Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.
PMID: 38666340
Eur Heart J · 2024
0.90
3
Mitochondrial Amount Determines Doxorubicin-Induced Cardiotoxicity in Cardiomyocytes.
PMID: 39921259
Adv Sci (Weinh) · 2025
0.80
4
Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.
PMID: 38589685
Acta Pharmacol Sin · 2024
0.70
5
Neutrophil extracellular traps promote fibrous vascular occlusions in chronic thrombosis.
PMID: 33512471
Blood · 2021
0.60