DNASE2
Function
Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the clearance of nucleic acids generated through apoptosis, hence preventing autoinflammation (PubMed:29259162, PubMed:31775019). Necessary for proper fetal development and for definitive erythropoiesis in fetal liver and bone marrow, where it degrades nuclear DNA expelled from erythroid precursor cells (PubMed:29259162).
Involvement in disease
Autoinflammatory-pancytopenia syndrome
AIPCS
An autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging.
None
The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.G116A, associated with AIPCS, has been shown to predominantly affect splicing, leading to in-frame deletion of exon 4, encoding amino acids 116 to 171. The protein resulting from this aberrant splicing may be unstable.
Post-translational modifications
Glycosylated. Genetic variations that affect N-glycosylation sites reduce activity, but enzymatic deglycosylation has no effect.
Sequence Similarities
Belongs to the DNase II family.
Tissue Specificity
Expressed in monocytes/macrophages (at protein level).
Cellular localization
- Lysosome
Alternative names
DNASE2A, DNL2, DNASE2, Deoxyribonuclease-2-alpha, Acid DNase, Deoxyribonuclease II alpha, Lysosomal DNase II, R31240_2, DNase II alpha