Alt. symbols: DNL1

Approved name: deoxyribonuclease 1
Alt. names: deoxyribonuclease I

Location: 16p13.3: 3611728 - 3680143 (+)
Gene type: protein_coding, 14 transcripts.

Scores: LoFtool: 0.609000 | pLI: 0.00000000 | LOEUF: 1.948

HGNC: 2956

NCBI: 1773, RefSeq: NG_009285.1

Ensembl: ENSG00000213918.11

LRG_ | Status: none

OMIM: 125505

Expression | ProteinAtlas

DNASE1 encodes a serum endonuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PMID: 2251263, 11241278, 2277032). Expressed by non-hematopoietic tissues, DNase I is the major serum endonuclease that degrades protein-free extracellular dsDNA into trioligonucleotides or tetraoligonucleotides. It has been reported to bind G-actin and block actin polymerization, and also plays a role in cell death by apoptosis (PMID:11241278, 14971053), possibly through modulation of FAS expression. Together with DNASE1L3, DNase I plays a key role in degrading neutrophil extracellular traps (NETs), which are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation. Intravascular NETs are thought to contribute to vasculitic end-organ damage in autoimmune diseases.

DNase I-deficient mice show classic systemic lupus erythematosus (SLE) findings, including ANA positivity, immune complex deposition in glomeruli, progression to glomerulonephritis and eventual death (PMID: 30758851). Congruently, heterozygous nonsense mutations in exon 2 of DNASE1 have been linked to SLE in 2 individuals, corresponding to decreased DNase I activity and extremely high IgG titers against nucleosomal antigens (PMID: 11479590) [MIM:152700]. Another study did not find evidence linki ng these 2 variants to autoimmune diseases in a Tunisian patient cohort (PMID: 19360410). Decreased DNase I activity has also been reported for other autoimmune diseases including Sjogren’s syndrome (PMID: 30273262), thyroid autoimmunity (PMID: 19022625, 23225239) and inflammatory bowel disease (PMID: 21687600). In the last case, a cohort of 110 IBD patients (aged 35 ± 12 years) was compared to 50?SLE patients and 50 healthy blood donors and the authors found that serum DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients. [Load More]