DNASE1

deoxyribonuclease 1

Basic information

Region (hg38): 16:3611728-3680143

Previous symbols: [ "DNL1" ]

Links

ENSG00000213918 ∙ NCBI:1773 ∙ OMIM:125505 ∙ HGNC:2956 ∙ Uniprot:P24855 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• systemic lupus erythematosus (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal systemic lupus erythematosus type 16 (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNASE1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNASE1 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				11	2	13
missense			12	4	4	20
nonsense		1				1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			60	31	15	106
Total	0	1	74	46	21

Variants in DNASE1

This is a list of pathogenic ClinVar variants found in the DNASE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-3655386-A-T		Systemic lupus erythematosus, susceptibility to	risk factor (Aug 01, 2001)
16-3655426-A-C		not specified	Uncertain significance (Nov 05, 2021)
16-3655434-G-A		not specified	Uncertain significance (Apr 26, 2024)
16-3655453-C-T			Uncertain significance (Jul 06, 2021)
16-3655464-C-T		Systemic lupus erythematosus	Likely pathogenic (Apr 04, 2024)
16-3655478-G-C			Likely benign (Jul 01, 2024)
16-3655492-A-G		not specified	Uncertain significance (Mar 31, 2022)
16-3655499-C-T		DNASE1-related disorder	Likely benign (Dec 05, 2019)
16-3655869-C-T		DNASE1-related disorder	Likely benign (Jun 05, 2019)
16-3655934-A-C		DNASE1-related disorder	Uncertain significance (Apr 26, 2024)
16-3656145-G-C		not specified	Uncertain significance (Sep 20, 2022)
16-3656165-G-A			Likely benign (Dec 01, 2023)
16-3656184-A-G			Benign (Sep 01, 2022)
16-3656642-G-C		not specified	Uncertain significance (Apr 18, 2023)
16-3656667-A-C			Benign (May 01, 2024)
16-3656695-C-T		DNASE1-related disorder	Likely benign (Apr 25, 2019)
16-3656696-G-A		Systemic lupus erythematosus	Benign (-)
16-3656702-G-A		Systemic lupus erythematosus	Uncertain significance (Jun 09, 2022)
16-3656715-G-A		Systemic lupus erythematosus	Uncertain significance (Mar 26, 2024)
16-3656727-T-C			Uncertain significance (Aug 14, 2023)
16-3656979-C-T			Uncertain significance (May 01, 2020)
16-3657001-G-A			Likely benign (Mar 01, 2022)
16-3657015-C-T			Likely benign (May 01, 2024)
16-3657022-C-G		DNASE1-related disorder	Benign (Jan 14, 2020)
16-3657063-C-T		DNASE1-related disorder	Likely benign (Jan 02, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNASE1	protein_coding	protein_coding	ENST00000246949	8	68416

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.98e-21	0.0000343	125539	0	209	125748	0.000831

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.55	264	170	1.55	0.0000111	1821
Missense in Polyphen		112	72.222	1.5508		795
Synonymous	-3.56	121	80.4	1.51	0.00000624	568
Loss of Function	-2.34	25	15.2	1.65	8.02e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00136	0.00136
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000659	0.000598
Finnish	0.000421	0.000416
European (Non-Finnish)	0.000686	0.000677
Middle Eastern	0.000659	0.000598
South Asian	0.00215	0.00213
Other	0.000985	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:2251263, PubMed:11241278, PubMed:2277032). Expressed by non-hematopoietic tissues and preferentially cleaves protein-free DNA (By similarity). Among other functions, seems to be involved in cell death by apoptosis (PubMed:11241278). Binds specifically to G- actin and blocks actin polymerization (By similarity). Together with DNASE1L3, 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:P00639, ECO:0000250|UniProtKB:P21704, ECO:0000250|UniProtKB:P49183, ECO:0000269|PubMed:11241278, ECO:0000269|PubMed:2251263, ECO:0000269|PubMed:2277032}.
• Disease: DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: 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:11479590, ECO:0000269|PubMed:20439745}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Neutrophil extracellular traps (NETs) are impaired in patients suffering from SLE (PubMed:20439745). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:20439745). {ECO:0000269|PubMed:20439745}.

Recessive Scores

• pRec: 0.356

Intolerance Scores

• loftool: 0.609
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.63

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.170
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.606

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnase1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: DNA catabolic process, endonucleolytic;neutrophil activation involved in immune response;regulation of acute inflammatory response;DNA catabolic process;apoptotic process;regulation of neutrophil mediated cytotoxicity
• Cellular component: extracellular region;nucleus;nuclear envelope;extracellular exosome
• Molecular function: DNA binding;actin binding;deoxyribonuclease I activity;deoxyribonuclease activity;protein binding