GeneBe

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
  • systemic lupus erythematosus (Supportive), mode of inheritance: Unknown

ClinVar

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

  • not_provided (27 variants)
  • not_specified (24 variants)
  • DNASE1-related_disorder (10 variants)
  • Systemic_lupus_erythematosus (8 variants)
  • Systemic_lupus_erythematosus,_susceptibility_to (1 variants)

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. These statistics are base on transcript: NM_000005223.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
11
clinvar
2
clinvar
 13
missense
32
clinvar
4
clinvar
4
clinvar
 40
nonsense
1
clinvar
2
clinvar
 3
start loss
0
frameshift
4
clinvar
 4
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total 0 1 39 15 6
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DNASE1protein_codingprotein_codingENST00000246949 868416
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
6.98e-210.000034312553902091257480.000831
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-2.552641701.550.00001111821
Missense in Polyphen11272.2221.5508795
Synonymous-3.5612180.41.510.00000624568
Loss of Function-2.342515.21.658.02e-7158

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001360.00136
Ashkenazi Jewish0.0001990.000198
East Asian0.0006590.000598
Finnish0.0004210.000416
European (Non-Finnish)0.0006860.000677
Middle Eastern0.0006590.000598
South Asian0.002150.00213
Other0.0009850.000978

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

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