DNASE1

Chr 16AD

deoxyribonuclease 1

Also known as: DNL1, DRNI

The protein is a serum endonuclease that cleaves DNA and degrades neutrophil extracellular traps to prevent clot formation during inflammation. Mutations cause systemic lupus erythematosus, an autoimmune disease with autosomal codominant inheritance. The gene shows extremely low constraint against loss-of-function variants, suggesting tolerance to reduced protein levels.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismADLOEUF 1.951 OMIM phenotype
Clinical SummaryDNASE1
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Gene-Disease Validity (ClinGen)
systemic lupus erythematosus · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -2.34
OE 1.65 (1.171.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.55Z-score
OE missense 1.55 (1.401.72)
264 obs / 170.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.65 (1.171.95)
00.351.4
Missense OE1.55 (1.401.72)
00.61.4
Synonymous OE1.51
01.21.6
LoF obs/exp: 25 / 15.2Missense obs/exp: 264 / 170.5Syn Z: -3.56
DN
0.6357th %ile
GOF
0.5759th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DNASE1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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