HGNC Approved Gene Symbol: DNASE1L3
Cytogenetic location: 3p14.3 Genomic coordinates (GRCh38): 3:58,192,257-58,210,972 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p14.3 | Systemic lupus erythematosus 16 | 614420 | Autosomal recessive | 3 |
Rodriguez et al. (1997) identified 3 human liver expressed sequence tags (ESTs) with homology to DNASE1 (125505) and used them to clone the DNASE1L3 gene. The predicted 305-amino acid DNASE1L3 protein includes an 18-amino acid putative signal peptide. Rodriguez et al. (1997) found the DNASE1L3 amino acid sequence to be 46% identical to that of DNASE1. On Northern blots, the 1.25-kb DNASE1L3 mRNA was expressed primarily in liver.
Independently, Zeng et al. (1997) identified a DNASE1L3 EST in a spleen cDNA library. The predicted 306-amino acid protein was 45% identical to that of DNASE1. Northern blot analysis showed that DNASE1L3 was expressed primarily in spleen and liver cells. The predominant mRNA was 1.3 kb, although there were 2 other transcripts. The purified recombinant protein had DNase activity in vitro that, unlike that of DNASE1, was not inhibited by G-actin.
By fluorescence in situ hybridization and PCR of a radiation hybrid panel, Rodriguez et al. (1997) mapped the DNASE1L3 gene to chromosome 3p21.1-p14.3.
In affected members of 6 consanguineous Arab families with systemic lupus erythematosus mapping to chromosome 3p14.3 (SLEB16; 614420), Al-Mayouf et al. (2011) identified homozygosity for a 1-bp deletion in the DNASE1L3 gene (643delT; 602244.0001) that segregated with disease in all 6 families. Haplotype analysis confirmed this to be a founder mutation.
In affected members of 6 consanguineous Arab families with systemic lupus erythematosus (SLEB16; 614420), Al-Mayouf et al. (2011) identified homozygosity for a 1-bp deletion (643delT) in the DNASE1L3 gene. The mutation segregated perfectly with the disease state in a strictly mendelian, fully penetrant, and autosomal recessive fashion in all 6 families, and was not found in 192 ethnically matched controls. Haplotype analysis confirmed this to be a founder mutation. In lymphoblast cell lines from 2 patients, no DNASE1L3 transcript was detected, and tissue culture studies demonstrated that mutant DNASE1L3 completely lacks DNase activity.
Al-Mayouf, S. M., Sunker, A., Abdwani, R., Al Abrawi, S., Almurshedi, F., Alhashmi, N., Al Sonbul, A., Sewairi, W., Qari, A., Abdallah, E., Al-Owain, M., Al Motywee, S., Al-Rayes, H., Hashem, M., Khalak, H., Al-Jebali, L., Alkuraya, F. S. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nature Genet. 43: 1186-1188, 2011. [PubMed: 22019780] [Full Text: https://doi.org/10.1038/ng.975]
Rodriguez, A. M., Rodin, D., Nomura, H., Morton, C. C., Weremowicz, S., Schneider, M. C. Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I. Genomics 42: 507-513, 1997. [PubMed: 9205125] [Full Text: https://doi.org/10.1006/geno.1997.4748]
Zeng, Z., Parmelee, D., Hyaw, H., Coleman, T. A., Su, K., Zhang, J., Gentz, R., Ruben, S., Rosen, C., Li, Y. Cloning and characterization of a novel human DNase. Biochem. Biophys. Res. Commun. 231: 499-504, 1997. [PubMed: 9070308] [Full Text: https://doi.org/10.1006/bbrc.1996.5923]