DNASE1L3

deoxyribonuclease 1 like 3

Basic information

Region (hg38): 3:58192257-58214697

Links

ENSG00000163687 ∙ NCBI:1776 ∙ OMIM:602244 ∙ HGNC:2959 ∙ Uniprot:Q13609 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal systemic lupus erythematosus type 16 (Moderate), mode of inheritance: AR
• autosomal systemic lupus erythematosus type 16 (Strong), mode of inheritance: AR
• hypocomplementemic urticarial vasculitis (Supportive), mode of inheritance: AR
• autosomal systemic lupus erythematosus type 16 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Systemic lupus erythematosus 16	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Allergy/Immunology/Infectious	22019780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNASE1L3 gene.

• not provided (6 variants)
• Autosomal systemic lupus erythematosus type 16 (2 variants)
• DNASE1L3-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNASE1L3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	51	3	56
missense		1	87	5	2	95
nonsense		1				1
start loss			1			1
frameshift	6		1			7
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region			8	9	1	18
non coding			1	28	6	35
Total	6	5	92	84	11

Highest pathogenic variant AF is 0.000151

Variants in DNASE1L3

This is a list of pathogenic ClinVar variants found in the DNASE1L3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-58192687-C-A			Uncertain significance (Dec 04, 2021)
3-58192695-G-A			Uncertain significance (Sep 19, 2022)
3-58192699-G-C		Inborn genetic diseases	Uncertain significance (Apr 01, 2024)
3-58192702-C-G			Uncertain significance (Mar 23, 2023)
3-58192705-T-C			Likely benign (Aug 21, 2023)
3-58192729-T-A		Inborn genetic diseases	Uncertain significance (Jun 28, 2023)
3-58192745-A-G			Uncertain significance (Jun 15, 2023)
3-58192751-C-T		Autosomal systemic lupus erythematosus type 16	Uncertain significance (Jun 20, 2022)
3-58192753-T-C			Likely benign (Dec 25, 2023)
3-58192790-C-G			Uncertain significance (Aug 17, 2021)
3-58192792-G-A			Likely benign (Nov 14, 2022)
3-58192802-G-C		Autosomal systemic lupus erythematosus type 16	Uncertain significance (Dec 11, 2023)
3-58192806-A-G			Uncertain significance (Aug 16, 2022)
3-58192809-A-T			Likely benign (Sep 26, 2022)
3-58192812-A-C			Likely benign (Mar 20, 2022)
3-58192818-G-C			Likely benign (May 04, 2022)
3-58192821-A-G			Likely benign (Jun 15, 2021)
3-58192823-G-C			Uncertain significance (Apr 25, 2022)
3-58193301-T-C		not specified	Benign (Jan 24, 2024)
3-58193326-C-G		Autosomal systemic lupus erythematosus type 16	Likely benign (Dec 06, 2023)
3-58193329-G-A			Likely benign (Jul 30, 2022)
3-58193333-G-T			Likely benign (Jan 26, 2024)
3-58193336-A-T			Likely benign (Nov 17, 2022)
3-58193339-T-C			Uncertain significance (Aug 09, 2022)
3-58193344-T-C			Uncertain significance (Nov 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNASE1L3	protein_coding	protein_coding	ENST00000318316	8	22441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000300	0.802	125712	0	35	125747	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0255	177	176	1.01	0.00000978	2036
Missense in Polyphen		64	68.263	0.93755		810
Synonymous	0.124	67	68.3	0.981	0.00000408	553
Loss of Function	1.23	9	14.0	0.644	5.88e-7	182

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000453	0.000453
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000202	0.000202
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity). {ECO:0000250|UniProtKB:O55070, ECO:0000250|UniProtKB:O89107, ECO:0000269|PubMed:10807908, ECO:0000269|PubMed:14646506, ECO:0000269|PubMed:23229555, ECO:0000269|PubMed:24312463, ECO:0000269|PubMed:27293190, ECO:0000269|PubMed:9070308, ECO:0000269|PubMed:9714828}.
• Disease: DISEASE: Systemic lupus erythematosus 16 (SLEB16) [MIM:614420]: A rare autosomal recessive form of systemic lupus erythematosus with childhood onset, characterized by high frequency of anti- neutrophil cytoplasmic antibodies and lupus nephritis. Systemic lupus erythematosus is a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:22019780}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0990

Intolerance Scores

• loftool: 0.545
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.155
• hipred: N
• hipred_score: 0.380
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.823

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dnase1l3
• Phenotype: cellular phenotype

Gene ontology

• Biological process: DNA catabolic process, endonucleolytic;neutrophil activation involved in immune response;regulation of acute inflammatory response;DNA metabolic process;DNA catabolic process;apoptotic DNA fragmentation;programmed cell death involved in cell development;regulation of neutrophil mediated cytotoxicity
• Cellular component: extracellular region;nucleus;endoplasmic reticulum
• Molecular function: DNA binding;deoxyribonuclease I activity;deoxyribonuclease activity;calcium ion binding