Affinage

NAT2

Arylamine N-acetyltransferase 2 · UniProt P11245

Length
290 aa
Mass
33.6 kDa
Annotated
2026-06-10
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NAT2 is a phase II xenobiotic-metabolizing enzyme that uses acetyl-CoA to acetylate aromatic and heterocyclic amines, governing both their detoxification and their carcinogenic activation (PMID:8353847). It catalyzes N-acetylation, which deactivates carbocyclic arylamines such as 4-aminobiphenyl, and O-acetylation of N-hydroxy intermediates, which generates DNA-adduct-forming reactive species; NAT2 displays higher apparent affinity than NAT1 for several carbocyclic arylamines but, unlike NAT1, does not mediate intramolecular N,O-acetyltransfer (PMID:8353847). The bioactivating arm of this chemistry is genotype-dependent: in cells co-expressing CYP1A2, the rapid-acetylator NAT2*4 allele produces more mutagenicity and DNA adducts from the heterocyclic amine AalphaC than the slow-acetylator NAT2*5B allele (PMID:19243127). Common allelic variation also dictates drug clearance, with NAT2 genotype explaining the bulk of isoniazid clearance variability and showing a clear gene-dose relationship between the number of active alleles and isoniazid and acetylisoniazid exposure (PMID:27528266, PMID:21980963). The enzyme is expressed most highly in liver, small intestine, and colon, with localization to intestinal, urothelial, and respiratory epithelial cells (PMID:10746928, PMID:17287389), and is transcribed from a promoter bearing an atypical TATA box and an Sp1 element (PMID:12904181); its expression is modulated by hypoxia (PMID:24557547) and by promoter methylation (PMID:32364660). Beyond classical arylamines, NAT2 acetylates endogenous aliphatic amines, performing regioselective N8-acetylation of monoacetylspermidine to form diacetylspermidine, with intracellular levels tracking acetylator phenotype (PMID:32497306).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 Medium

    Establishing a non-invasive readout of hepatic NAT2 activity required a validated metabolic index; the caffeine metabolite AFMU/1-methylxanthine ratio answered this and enabled large-scale phenotyping.

    Evidence Pharmacokinetic analysis of caffeine urinary metabolites across human populations

    PMID:1306111

    Open questions at the time
    • Does not establish enzyme mechanism or substrate scope
    • Ratio reflects net hepatic activity, not allele-specific kinetics
  2. 1993 High

    Whether NAT2 both detoxifies and activates carcinogens was unresolved; reconstituted recombinant enzyme showed it catalyzes N-acetylation (deactivation) and acetyl-CoA-dependent O-acetylation (activation) of arylamines, distinguishing its substrate preferences and reaction repertoire from NAT1.

    Evidence In vitro enzymatic assays with recombinant human NAT2 against 17 arylamines plus DNA adduct measurement

    PMID:8353847

    Open questions at the time
    • No structural basis for substrate selectivity
    • Tissue-level contribution to in vivo activation not addressed
  3. 1995 Medium

    The question of which acetyltransferase drives arylamine bioactivation in target bladder tissue was tested; NAT2 activity was undetectable in bladder cytosols and DNA adducts correlated with NAT1, not NAT2, defining the tissue-specific division of labor.

    Evidence Biochemical activity and 32P-postlabeling DNA adduct assays in human bladder cytosols with genotyping

    PMID:7585581

    Open questions at the time
    • Single-tissue conclusion
    • Does not exclude NAT2 contribution in other target organs
  4. 2000 Medium

    Where NAT2 acts was unknown at cellular resolution; in situ hybridization localized NAT2 mRNA to epithelial cells of gut, urinary tract, and airway, linking expression to barrier tissues exposed to ingested and inhaled amines.

    Evidence In situ hybridization histochemistry on human tissue sections

    PMID:10746928

    Open questions at the time
    • mRNA localization not confirmed at protein level
    • Single method
  5. 2003 High

    Whether Nat enzymes are the sole route of arylamine N-acetylation in vivo was tested with double-knockout mice, which lost all N-acetyltransferase activity and acetylated metabolites, establishing Nat1/Nat2 as the exclusive acetylating enzymes.

    Evidence Nat1/Nat2 double-knockout mouse with tissue enzyme assays and in vivo pharmacokinetics

    PMID:12815173

    Open questions at the time
    • Mouse Nat orthology to human NAT2 not strictly equivalent
    • Does not separate individual Nat1 vs Nat2 contributions
  6. 2003 Medium

    How NAT2 is transcribed was undefined; promoter analysis revealed an atypical TATA box and an Sp1 element both essential for activity, identifying the core regulatory architecture.

    Evidence Promoter-reporter deletion/mutation analysis, DNase I footprinting, and transcription start site mapping in mouse Nat2

    PMID:12904181

    Open questions at the time
    • Identity of the Sp1-box-binding factor not confirmed
    • Mouse promoter may differ from human
  7. 2006 High

    Whether loss of Nat2 activity reflects transcriptional or post-translational change was tested; single-gene knockout abolished protein and activity without affecting Nat1, attributing function specifically to Nat2 protein.

    Evidence Nat2 knockout mouse with qRT-PCR, Western blot, and N-/O-acetylation activity assays

    PMID:16857729

    Open questions at the time
    • Mouse-to-human extrapolation
    • Does not address allele-specific protein stability
  8. 2007 Medium

    Quantitative tissue distribution and transcript structure were unresolved; cross-tissue qRT-PCR and 5'-RACE placed highest NAT2 expression in liver, small intestine, and colon and mapped the predominant liver transcription start sites.

    Evidence TaqMan qRT-PCR across 29 human tissues and cap-dependent 5'-RACE

    PMID:17287389

    Open questions at the time
    • mRNA abundance not linked to protein or activity per tissue
    • Single lab
  9. 2009 High

    Whether the rapid-acetylator genotype increases genotoxic bioactivation was tested; in CYP1A2-coexpressing cells, NAT2*4 yielded more mutagenicity and DNA adducts from AalphaC than NAT2*5B, mechanistically linking acetylator phenotype to carcinogen activation.

    Evidence CHO cells co-expressing CYP1A2 with NAT2*4 or NAT2*5B; hprt mutagenicity and LC-MS/MS adduct quantification

    PMID:19243127

    Open questions at the time
    • Single carcinogen tested
    • In vivo cancer risk not directly measured
  10. 2011 Medium

    The relationship between allele number and drug exposure was quantified; a gene-dose study showed progressive increases in isoniazid AUC and decreases in acetylisoniazid AUC with fewer active NAT2 genes.

    Evidence Controlled human pharmacokinetic study stratified by NAT2 genotype with HPLC metabolite measurement

    PMID:21980963

    Open questions at the time
    • Single population
    • Limited subject number
  11. 2014 Medium

    Whether physiological conditions regulate NAT2 was tested; acute hypoxia downregulated NAT2 mRNA and activity in vivo, demonstrating transcriptional environmental control of the enzyme.

    Evidence In vivo rat altitude model with probe-drug pharmacokinetics, ELISA, and real-time PCR

    PMID:24557547

    Open questions at the time
    • Rat model
    • Mechanism linking hypoxia signaling to the promoter not defined
  12. 2016 Medium

    The extent to which genotype determines isoniazid clearance, and how this changes developmentally, was clarified; genotype explained 88% of clearance variability in adults but was superseded by substrate concentration in young children until enzyme maturation by ~5.3 years.

    Evidence Population PK/PD Michaelis-Menten modeling in children with MARS predictor analysis

    PMID:27528266

    Open questions at the time
    • Small pediatric cohort
    • Molecular basis of age-dependent maturation unknown
  13. 2019 Low

    Whether epigenetic regulation modifies NAT2-dependent drug response was examined; promoter hypermethylation associated with anti-tuberculosis drug-induced liver injury independent of acetylator genotype, implicating methylation in expression control.

    Evidence Case-control bisulfite sequencing/mass spectrometry of NAT2 promoter with genotyping

    PMID:32364660

    Open questions at the time
    • No functional validation that methylation alters NAT2 expression
    • Association only, single cohort
  14. 2020 Medium

    Whether NAT2 has endogenous substrates beyond xenobiotic amines was tested; it performs regioselective N8-acetylation of monoacetylspermidine to diacetylspermidine and acetylates alkylamine drugs, expanding its physiological substrate scope.

    Evidence Metabolomics of cells expressing rapid vs slow acetylator NAT2 with chemical synthesis confirmation

    PMID:32497306

    Open questions at the time
    • Physiological consequence of polyamine acetylation unknown
    • Single lab, two methods

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural determinants distinguishing N- versus O-acetylation and the broad alkylamine/polyamine substrate selectivity, and the in vivo physiological role of NAT2-mediated polyamine acetylation, remain unresolved.
  • No structural model linking active site to regioselectivity in the corpus
  • Physiological function of diacetylspermidine production undefined
  • Transcription factor mediating hypoxia/methylation control not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-9748784 Drug ADME 2

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Recombinant human NAT2 catalyzes both N-acetylation (deactivation) and O-acetylation (activation) of arylamine carcinogens. NAT2 showed significantly higher apparent affinity than NAT1 for carbocyclic arylamines such as 4-aminobiphenyl and beta-naphthylamine. NAT2 catalyzed acetyl-CoA-dependent O-acetylation of N-hydroxy-2-aminofluorene and N-hydroxy-4-aminobiphenyl to yield DNA adducts; however, NAT2 did not detectably catalyze intramolecular N,O-acetyltransferase-mediated activation of N-hydroxy-acetylarylamines (unlike NAT1). In vitro enzymatic assay using recombinant human NAT2 expressed in E. coli; N-acetylation and O-acetylation of 17 arylamines tested; DNA adduct formation measured Carcinogenesis High 8353847
1995 NAT2 activity (measured as N-acetylation of sulfamethazine) was below the limit of detection in human urinary bladder tissue cytosols, indicating that NAT2 does not contribute detectably to O-acetylation of N-hydroxy arylamines in bladder mucosa; DNA adduct levels in bladder correlated with NAT1 activity but not NAT2-dependent O-acetyltransferase activity. Biochemical enzyme activity assays in human bladder cytosols (N-acetylation of PABA for NAT1, SMZ for NAT2, O-acetylation of N-hydroxy-4-aminobiphenyl); 32P-postlabeling for DNA adducts; NAT1/NAT2 genotyping by PCR Cancer research Medium 7585581
2000 NAT2 mRNA is expressed in human liver, gastrointestinal tract (esophagus, stomach, small intestine, colon), ureter, bladder, and lung, with expression localized specifically to intestinal epithelial cells, urothelial cells, and respiratory bronchiolar epithelial cells, as determined by in situ hybridization histochemistry. In situ hybridization histochemistry using NAT2-specific riboprobes on formalin-fixed, paraffin-embedded human tissue sections Toxicological sciences Medium 10746928
2003 Nat1/Nat2 double-knockout mice completely lack N-acetyltransferase activity toward p-aminosalicylate in all tissues (liver, kidney, colon, brain, bladder, spleen), and show severely impaired in vivo pharmacokinetics of p-aminosalicylate and sulfamethazine with absent acetylated metabolites, confirming that Nat1 and Nat2 together are the sole enzymes responsible for arylamine N-acetylation in mice. Gene targeting knockout mouse; RT-PCR for mRNA; in vitro N-acetylation enzyme assays in tissue cytosols; in vivo pharmacokinetic studies with plasma metabolite measurement Molecular pharmacology High 12815173
2003 The mouse Nat2 gene has a single promoter containing an atypical TATA box and an Sp1 box; deletion or mutation of either element severely reduces promoter activity. The Sp1 box region binds cellular protein and resists DNase I digestion. The transcription start site is 6.5 kb upstream of the coding region adjacent to a non-coding exon, with alternative splicing of a single 6.2 kb intron. Promoter-reporter (lacZ) fusion constructs with deletion and mutation analysis; DNase I footprinting; transcription start site mapping; RT-PCR and database analysis of cDNA The Biochemical journal Medium 12904181
2006 Mouse Nat2 knockout eliminates Nat2 protein and catalytic activity (including N-acetylation of 4-aminobiphenyl and O-acetylation of N-hydroxy-4-aminobiphenyl) in all tissues without significantly affecting Nat1 mRNA or activity, demonstrating that loss of Nat2 protein (not mRNA) accounts for the loss of activity. Nat2 knockout mouse; quantitative RT-PCR for Nat1 and Nat2 mRNA; enzyme activity assays for N-acetylation and O-acetylation in tissue cytosols; Western blot for Nat2 protein The Journal of pharmacology and experimental therapeutics High 16857729
2007 NAT2 mRNA is highest in human liver, small intestine, and colon and is detectable in most other tissues at lower levels. The predominant NAT2 liver transcription start sites are at positions -8711 and -8716 relative to the ORF exon, with direct splicing to the ORF exon and no additional non-coding exons detected. TaqMan quantitative RT-PCR with intron-spanning primers across 29 human tissues; cap-dependent 5'-RACE amplification for transcription start site mapping; review of public cDNA databases Drug metabolism and disposition Medium 17287389
2009 The NAT2*4 (rapid/wild-type) allele produces significantly more mutagenicity and dG-C8-AalphaC DNA adducts from the heterocyclic amine AalphaC than the NAT2*5B (slow acetylator) allele in CHO cells co-expressing human CYP1A2, demonstrating that NAT2 rapid acetylator genotype enhances genotoxic bioactivation of this carcinogen via O-acetylation of the N-hydroxy intermediate. CHO cells stably transfected with human CYP1A2 and NAT2*4 or NAT2*5B; mutagenicity assay at hprt locus; DNA adduct quantification by LC-MS/MS Chemical research in toxicology High 19243127
2020 Human NAT2 acetylates aliphatic endogenous amines in addition to aromatic amines: specifically, NAT2 performs regioselective N8-acetylation of monoacetylspermidine to form diacetylspermidine. Intracellular diacetylspermidine concentrations are higher in cells expressing rapid versus slow acetylator NAT2. NAT2 also selectively acetylates structurally diverse alkylamine-containing drugs. Metabolomic analysis of human cell lines expressing rapid vs. slow acetylator NAT2 phenotype; chemical synthesis of acetylated metabolites for structural confirmation; substrate profiling of alkylamine drugs Angewandte Chemie (International ed. in English) Medium 32497306
1992 NAT2 catalyzes the acetylation of a caffeine metabolite to produce 5-acetylamino-6-formylamino-3-methyluracil (AFMU); the urinary molar ratio of AFMU/1-methylxanthine after caffeine ingestion is a valid phenotyping index for hepatic NAT2 activity, even in alkaline urines. Pharmacokinetic analysis of caffeine urinary metabolites in human subjects (n=12 for validation, n=274 across populations); correlation of AFMU/1-methylxanthine ratio with NAT2 phenotype Pharmacogenetics Medium 1306111
2014 Acute high-altitude hypoxia downregulates NAT2 activity and mRNA expression in rats in vivo, while chronic high-altitude hypoxia upregulates CYP2D6 but does not reverse NAT2 downregulation, demonstrating that hypoxic conditions regulate NAT2 at the transcriptional level. In vivo rat model at different altitudes; probe drug pharmacokinetics by HPLC; ELISA for protein expression; real-time PCR for mRNA Pharmacology Medium 24557547
2016 NAT2 genotype explains 88% of isoniazid clearance variability in adults. In children, isoniazid concentration itself predicts both NAT2 Vmax and Km and supersedes NAT2 genotype as a determinant of enzyme kinetics. NAT2 genotype contribution to enzyme maturation is modified non-linearly by age until maturation at ≥5.3 years. Population pharmacokinetic/pharmacodynamic modeling using Michaelis-Menten kinetics in 30 children; MARS (multivariate adaptive regression splines) to identify predictors; measurement of isoniazid elimination and N-acetylisoniazid production EBioMedicine Medium 27528266
2019 NAT2 promoter hypermethylation (at CpG5, CpG10, CpG11.12 sites) is independently associated with anti-tuberculosis drug-induced liver injury and correlates with increased ATLI risk independent of NAT2 acetylation genotype, suggesting that epigenetic regulation of NAT2 expression modulates drug metabolism. Case-control study; bisulfite sequencing and mass spectrometry for NAT2 promoter methylation; PCR-based NAT2 genotyping; binary logistic regression Journal of clinical pharmacy and therapeutics Low 32364660
2011 NAT2 genotype shows a dose-dependent (gene dose) effect on isoniazid pharmacokinetics: homozygous wild-type (wt/wt), heterozygous (m/wt), and homozygous mutant (m/m) subjects show progressively increasing isoniazid AUC and decreasing acetylisoniazid AUC, with a good linear relationship between pharmacokinetic parameters and number of active NAT2 genes. Controlled pharmacokinetic study in 24 healthy Chinese subjects stratified by NAT2 genotype; plasma concentrations of isoniazid and acetylisoniazid by HPLC; noncompartmental analysis Drug metabolism and drug interactions Medium 21980963

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 570 10667461
2005 NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet (London, England) 477 16112301
1992 Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 397 1306111
2002 Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutation research 364 12351146
1993 Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 327 8353847
1995 Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer research 202 7585581
1988 Separate genes encode functionally equivalent ADP/ATP carrier proteins in Saccharomyces cerevisiae. Isolation and analysis of AAC2. The Journal of biological chemistry 164 2844786
2000 Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicological sciences : an official journal of the Society of Toxicology 123 10746928
2008 Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history. BMC genetics 122 18304320
2000 NAT2 slow acetylation and bladder cancer risk: a meta-analysis of 22 case-control studies conducted in the general population. Pharmacogenetics 120 10761999
2003 Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population. British journal of clinical pharmacology 117 12814450
1996 Environmental air pollution and DNA adducts in Copenhagen bus drivers--effect of GSTM1 and NAT2 genotypes on adduct levels. Carcinogenesis 111 8640907
2010 NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 99 20392357
2009 Genetic polymorphism in N-Acetyltransferase (NAT): Population distribution of NAT1 and NAT2 activity. Journal of toxicology and environmental health. Part B, Critical reviews 98 20183529
2005 CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma. Mutation research 98 15914211
2008 The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery. Molecular biology of the cell 86 18614795
2007 Identification of N-acetyltransferase 2 (NAT2) transcription start sites and quantitation of NAT2-specific mRNA in human tissues. Drug metabolism and disposition: the biological fate of chemicals 78 17287389
1990 Structure-function studies of adenine nucleotide transport in mitochondria. II. Biochemical analysis of distinct AAC1 and AAC2 proteins in yeast. The Journal of biological chemistry 78 2167309
2002 Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer. Carcinogenesis 76 11872636
1997 Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferases, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours. Cytogenetics and cell genetics 72 9284941
2004 Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability. Human molecular genetics 71 15016764
2008 Interethnic and intraethnic variability of NAT2 single nucleotide polymorphisms. Current drug metabolism 70 18680468
1998 N-acetyltransferase NAT1 and NAT2 genotypes and lung cancer risk. Pharmacogenetics 69 9731715
1996 Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Pharmacogenetics 65 9014199
2007 Polymorphisms at XPD and XRCC1 DNA repair loci and increased risk of oral leukoplakia and cancer among NAT2 slow acetylators. International journal of cancer 64 17290401
1995 Lung cancer and mutations at the polymorphic NAT2 gene locus. Pharmacogenetics 64 8528267
2007 Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk. International journal of cancer 62 17290402
1997 Influence of GSTM1 and NAT2 genotypes on placental DNA adducts in an environmentally exposed population. Environmental and molecular mutagenesis 60 9329643
2003 Generation and functional characterization of arylamine N-acetyltransferase Nat1/Nat2 double-knockout mice. Molecular pharmacology 58 12815173
2014 Association of NAT2, GST and CYP2E1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity. Tuberculosis (Edinburgh, Scotland) 56 24637014
2009 Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population. Pharmacogenomics 56 19761367
2008 Unraveling ambiguous NAT2 genotyping data. Clinical chemistry 55 18664443
2009 Association of NAT2, GSTM1, GSTT1, CYP2A6, and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China. Cancer detection and prevention 52 19303722
2007 Association of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smoking. Asian Pacific journal of cancer prevention : APJCP 52 18159984
2004 Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae. Genetics 50 15238515
2005 Genetic polymorphisms in CYP1B1, GSTA1, NQO1 and NAT2 and the risk of lung cancer. Cancer letters 49 15808404
2000 GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients. Carcinogenesis 49 10607733
2004 Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas. International journal of cancer 48 14618622
1998 Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease. Neurology 45 9855506
1997 Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese populations. Pharmacogenetics 45 9429236
2008 Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 44 18768514
2003 N-acetyltransferase (NAT1, NAT2) and glutathione S-transferase (GSTM1, GSTT1) polymorphisms in breast cancer. Cancer letters 44 12860276
2006 Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men and women. BMC cancer 43 17026750
1999 NAT2 gene polymorphism as a possible marker for susceptibility to bladder cancer in Japanese. International journal of urology : official journal of the Japanese Urological Association 43 10510890
2007 NAT2 and CYP1A2 polymorphisms and lung cancer risk in relation to smoking status. Asian Pacific journal of cancer prevention : APJCP 42 17477782
2007 A meta-analysis of the association of N-acetyltransferase 2 gene (NAT2) variants with breast cancer. American journal of epidemiology 40 17535831
2006 N-acetyltransferase 2 (NAT2) gene polymorphisms in colon and lung cancer patients. BMC medical genetics 40 16827944
1997 CYP2D6, NAT2 and CYP2E1 genetic polymorphisms in nonagenarians. Age and ageing 40 9177672
2019 NAT2 variants and toxicity related to anti-tuberculosis agents: a systematic review and meta-analysis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 37 30871660
2019 Association of genetic polymorphisms of CYP2E1, NAT2, GST and SLCO1B1 with the risk of anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis. BMJ open 34 31375612
2000 Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis. Pharmacogenetics 33 10739170
2019 Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence. Bioscience reports 32 30509962
2014 Effect of exposure to acute and chronic high-altitude hypoxia on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats. Pharmacology 32 24557547
2009 GSTM1 and NAT2 polymorphisms and colon, lung and bladder cancer risk: a case-control study. Anticancer research 32 19443391
2007 NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans. Prostate cancer and prostatic diseases 32 18026184
2021 A Rapid Pharmacogenomic Assay to Detect NAT2 Polymorphisms and Guide Isoniazid Dosing for Tuberculosis Treatment. American journal of respiratory and critical care medicine 30 34375564
2016 Optimization of Clonazepam Therapy Adjusted to Patient's CYP3A Status and NAT2 Genotype. The international journal of neuropsychopharmacology 30 27639091
2011 The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid. Journal of clinical pharmacology 29 21558457
2003 Structure and transcriptional regulation of the Nat2 gene encoding for the drug-metabolizing enzyme arylamine N-acetyltransferase type 2 in mice. The Biochemical journal 29 12904181
2018 Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis. Antimicrobial agents and chemotherapy 28 29263072
2009 Association of NAT2 gene polymorphisms with susceptibility to esophageal and gastric cancers in the Kashmir Valley. Archives of medical research 28 19766908
2007 Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive pulmonary disease. Clinica chimica acta; international journal of clinical chemistry 28 17442289
2020 Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine N-Acetyltransferase NAT2. Angewandte Chemie (International ed. in English) 27 32497306
2023 NAT2 global landscape: Genetic diversity and acetylation statuses from a systematic review. PloS one 26 37023111
2014 Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole. Biochemical pharmacology 25 25241292
2002 GSTM-1 and NAT2 and genetic alterations in colon tumors. Cancer causes & control : CCC 25 12195642
2016 The Non-Linear Child: Ontogeny, Isoniazid Concentration, and NAT2 Genotype Modulate Enzyme Reaction Kinetics and Metabolism. EBioMedicine 24 27528266
2015 Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1. British journal of clinical pharmacology 24 25264565
1995 Expression of the AAC2 gene encoding the major mitochondrial ADP/ATP carrier in Saccharomyces cerevisiae is controlled at the transcriptional level by oxygen, heme and HAP2 factor. European journal of biochemistry 24 7758459
2022 Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models. European journal of clinical pharmacology 23 35852584
2018 N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians. European journal of clinical pharmacology 23 29589062
2008 [Genetic polymorphism in GST, NAT2, and MTRR and susceptibility to childhood acute leukemia]. Molekuliarnaia biologiia 23 18610829
2007 NAT2 variation and idiopathic talipes equinovarus (clubfoot). American journal of medical genetics. Part A 23 17726690
2017 Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan. Environmental health and preventive medicine 22 29165164
2011 NAT2 polymorphism and lung cancer risk: a meta-analysis. Lung cancer (Amsterdam, Netherlands) 22 21292342
2010 Synergistic effects of NAT2 slow and GSTM1 null genotypes on carcinogen DNA damage in the lung. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 22 20501762
2009 GSTT1, GSTM1, GSTM3 and NAT2 polymorphisms in laryngeal squamous cell carcinoma in a Greek population. The Journal of laryngology and otology 22 19922706
2014 Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population. BMC genetics 21 25544508
2011 Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients. Antimicrobial agents and chemotherapy 20 22106207
2008 Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers. Biochemical pharmacology 20 18703023
2006 N-acetyltransferase (Nat) 1 and 2 expression in Nat2 knockout mice. The Journal of pharmacology and experimental therapeutics 20 16857729
2004 Impact of GSTT1, GSTM1, GSTP1 and NAT2 genotypes on KRAS2 and TP53 gene mutations in colorectal cancer. International journal of cancer 20 15069679
1994 NAT2, an essential gene encoding methionine N alpha-acetyltransferase in the yeast Saccharomyces cerevisiae. The Journal of biological chemistry 20 8175741
2019 The role of NAT2 polymorphism and methylation in anti-tuberculosis drug-induced liver injury in Mongolian tuberculosis patients. Journal of clinical pharmacy and therapeutics 19 32364660
2008 Sequence variants of NAT1 and NAT2 and other xenometabolic genes and risk of lung and aerodigestive tract cancers in Central Europe. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19 18199719
2008 Quantitative tissue and gene-specific differences and developmental changes in Nat1, Nat2, and Nat3 mRNA expression in the rat. Drug metabolism and disposition: the biological fate of chemicals 19 18799802
2021 Association Between NAT2 Polymorphism and Lung Cancer Risk: A Systematic Review and Meta-Analysis. Frontiers in oncology 18 33777732
2019 NAT2 slow acetylator is associated with anti-tuberculosis drug-induced liver injury severity in indonesian population. Pharmacogenomics 18 31699005
2011 Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy, asthma & immunology research 18 21966608
2011 Gene dose effect of NAT2 variants on the pharmacokinetics of isoniazid and acetylisoniazid in healthy Chinese subjects. Drug metabolism and drug interactions 18 21980963
2002 Polymorphisms of arylamine N-acetyltransferase (NAT1 and NAT2) and larynx cancer susceptibility. ORL; journal for oto-rhino-laryngology and its related specialties 18 12037388
2015 NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. BMC cancer 17 25886288
2015 NAT2 gene diversity and its evolutionary trajectory in the Americas. The pharmacogenomics journal 17 26503810
2010 NAT2 polymorphism and gastric cancer susceptibility: a meta-analysis. Archives of medical research 17 20637371
2010 N-Acetyltransferase-2 (NAT2) gene polymorphisms and enzyme activity in Serbs: unprecedented high prevalence of rapid acetylators in a White population. Journal of clinical pharmacology 17 20801937
2009 The impact of NAT2 acetylator genotype on mutagenesis and DNA adducts from 2-amino-9H-pyrido[2,3-b]indole. Chemical research in toxicology 17 19243127
2000 Tissue- and gender-specific expression of N-acetyltransferase 2 (Nat2*) during development of the outbred mouse strain CD-1. Drug metabolism and disposition: the biological fate of chemicals 17 10640510
2008 Pleiotropic effects of the yeast Sal1 and Aac2 carriers on mitochondrial function via an activity distinct from adenine nucleotide transport. Molecular genetics and genomics : MGG 16 18431598
2006 N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease. BMC medical genetics 16 16571112
1995 A kluyveromyces lactis gene homologue to AAC2 complements the Saccaromyces cerevisiae op1 mutation. Current genetics 16 7736606

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