NAT2
Chr 8ARN-acetyltransferase 2
The encoded enzyme catalyzes N- or O-acetylation of arylamine and hydrazine substrates, participating in drug detoxification and carcinogen bioactivation. Mutations cause slow acetylation phenotype, which affects drug metabolism rates and is associated with increased cancer risk and drug toxicity. This follows autosomal recessive inheritance and shows low constraint against loss-of-function variants.
Primary Disease Associations & Inheritance
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
NAT2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Gene-guided N-acetyl Cysteine for Prophylaxis of Anti-tuberculous Drug- Induced Hepatitis
RECRUITINGA Genotype-Phenotype Urothelial Cancer Registry
ACTIVE NOT RECRUITINGSulfasalazine in AML Treated by Intensive Chemotherapy: Elderly Patients-first Line Treatment
RECRUITINGExternal Resources
Links to major genomics databases and tools