Alt. symbols: DNL | DNL2

Approved name: deoxyribonuclease 2, lysosomal
Alt. names: deoxyribonuclease II, lysosomal

Location: 19p13.13: 12875209 - 12881595 (-)
Gene type: protein_coding, 7 transcripts.

Scores: LoFtool: 0.497000 | pLI: 0.05373340 | LOEUF: 0.884

HGNC: 2960

NCBI: 1777, RefSeq: .0

Ensembl: ENSG00000105612.10

LRG_ | Status: none

OMIM: 126350

Expression | ProteinAtlas

DNASE2 encodes the DNase II endonuclease, which plays a central role in the clearance of intracellular nucleic acids, such as those generated through the phagocytosis of maturating erythroblast nuclei (PMID: 29259162).

Biallelic missense mutations in DNASE2, associated with a loss of DNase II endonuclease activity and lysosomal accumulation of undigested DNA, cause an autoinflammatory condition featuring severe early-onset cytopenias, hepatosplenomegaly, failure-to-thrive and recurrent fevers [OMIM: 619858] (PMID: 29259162, 31775019). Additionally reported clinical findings include chronic diarrhea, proteinuria with glomerulonephritis, liver fibrosis with transaminitis, deforming arthropathy, and vasculitic sk in lesions. Some patients may have developmental delay(s) and/or learning disabilities associated with subcortical white matter lesions on neuro-imaging. Patients show increased numbers of erythroblasts in their peripheral blood, produce increased amounts of anti-DNA antibodies and proinflammatory cytokines (TNF-α, MCP-1, IL-18, IL-1β, IL-8, type I and II IFNs), and show evidence of markedly enhanced type I IFN signaling as well as constitutive upregulation of phosphorylated STAT1 and STAT3 in their lymphocytes and monocytes. Consistent with these findings, some patients have been reported to respond to JAK1/2 blockade with baricitinib (PMID: 31775019). [Load More]