DNASE2

Chr 19AR

deoxyribonuclease 2, lysosomal

Also known as: AIPCS, DNASE2A, DNL, DNL2

NCBI Gene: 1777ENSG00000105612UniProt: O00115

This gene encodes a member of the DNase family. The protein, located in the lysosome, hydrolyzes DNA under acidic conditions and mediates the breakdown of DNA during erythropoiesis and apoptosis. Two codominant alleles have been characterized, DNASE2*L (low activity) and DNASE2*H (high activity), that differ at one nucleotide in the promoter region. The DNASE2*H allele is represented in this record. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Autoinflammatory-pancytopenia syndromeMIM #619858
AR
217
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNASE2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 98 VUS of 217 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 1.91
OE 0.49 (0.29–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.64Z-score
OE missense 0.87 (0.77–0.99)
170 obs / 195.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.29–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.77–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 8 / 16.3Missense obs/exp: 170 / 195.3Syn Z: 0.02

ClinVar Variant Classifications

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic2
VUS98
Likely Benign85
Benign7
Conflicting4
21
Pathogenic
2
Likely Pathogenic
98
VUS
85
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
18
0
21
Likely Pathogenic
0
0
2
0
2
VUS
2
80
15
1
98
Likely Benign
0
2
30
53
85
Benign
0
2
3
2
7
Conflicting
—4
Total2876856217

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DNASE2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Autoinflammatory-pancytopenia syndrome

MIM #619858

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland.
Xie HT et al.·Stem Cells Transl Med
2018
LAMP3 signature affects cervical cancer progression through autophagy.
Ji H et al.·BMC Cancer
2025
Multi-omic approach associates blood methylome with bronchodilator drug response in pediatric asthma.
Perez-Garcia J et al.·J Allergy Clin Immunol
2023
A young boy with rash, arthritis, and developmental delay: Monogenic lupus due to DNASE2 gene defect.
Basu S et al.·Int J Rheum Dis
2023Case report
Whole-exome analysis of adolescents with low VWF and heavy menstrual bleeding identifies novel genetic associations.
Sadler B et al.·Blood Adv
2022
Genetic diagnosis of autoinflammatory disease patients using clinical exome sequencing.
Batlle-Masó L et al.·Eur J Med Genet
2020Cohort
Functional Single Nucleotide Polymorphisms (SNPs) in the Genes Encoding the Human Deoxyribonuclease (DNase) Family Potentially Relevant to Autoimmunity.
Fujihara J et al.·Immunol Invest
2016Functional
Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells.
Takahashi A et al.·Nat Commun
2018
Seven nonsynonymous SNPs in the gene encoding human deoxyribonuclease II may serve as a functional SNP potentially implicated in autoimmune dysfunction.
Kimura-Kataoka K et al.·Electrophoresis
2013Functional
Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis.
Rossol M et al.·Arthritis Res Ther
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools