NAT2 rs1799929: What Your Genotype Means
The genetic variant rs1799929 is a synonymous single nucleotide polymorphism (c.481C>T, p.Leu161Leu) located in the coding region of the human NAT2 gene. Although it does not alter the amino acid sequence of the enzyme on its own, it serves as a critical tagging marker for the NAT2*5 haplotype cluster, which confers a slow drug acetylator phenotype. Understanding this variant provides key insights into how an individual may metabolize certain therapeutic drugs and environmental compounds.
What each genotype means
| Genotype | What the research suggests | Reading |
|---|---|---|
| CC | You carry two copies of the ancestral cytosine allele at position c.481. In the absence of other slow-conferring variants across the NAT2 gene, this genotype is compatible with normal or rapid enzyme activity. However, acetylator phenotype cannot be inferred without examining the full panel of NAT2 star alleles. | Informational |
| CT | You carry one copy of the reference C allele and one copy of the variant T allele. The presence of the T allele frequently indicates heterozygosity for a NAT2*5 cluster slow-acetylating haplotype. Depending on which variant is inherited on your complementary chromosome, your predicted overall phenotype may range from rapid to intermediate or slow. | Informational |
| TT | You carry two copies of the variant thymine allele at position c.481. This genotype indicates that both of your NAT2 alleles frequently belong to the NAT2*5 slow-acetylator lineage when paired with linked causal missense mutations. Individuals with this genotype typically exhibit reduced clearance of arylamine medications and warrant higher attention when using relevant prescription drugs. | Higher attention |
Variant Architecture and Molecular Context
The single nucleotide polymorphism rs1799929 is situated in the single coding exon of the N-acetyltransferase 2 (NAT2) gene on chromosome 8. At the nucleotide level, it represents a transition from cytosine to thymine at position 481 (c.481C>T). In protein nomenclature, this variant corresponds to p.Leu161Leu, meaning the codon change does not modify the encoded leucine residue. Because it is a synonymous mutation, the variant does not directly disrupt the primary catalytic domain or the three-dimensional folding of the NAT2 protein when isolated. Instead, its principal biological relevance in pharmacogenomics arises from its strong linkage disequilibrium with other functionally disruptive variants. Most notably, rs1799929 frequently co-segregates with the missense variant 341T>C (rs1801280, p.Ile114Thr), which significantly reduces the stability of the enzyme and leads to degraded clearance capacity in the liver.
Biological Function of the NAT2 Enzyme
The NAT2 gene encodes arylamine N-acetyltransferase 2, an essential Phase II xenobiotic-metabolizing enzyme predominantly expressed in human liver and intestinal tissues. NAT2 catalyzes the transfer of an acetyl group from acetyl-coenzyme A to aromatic amines, hydrazines, and heterocyclic amines. This chemical modification typically inactivates therapeutic compounds, facilitating their safe excretion from the body, though in some instances it can generate reactive intermediates. Clinically important substrates for NAT2 include the frontline tuberculosis medication isoniazid, the antibacterial agent dapsone, the antihypertensive drug hydralazine, and the anti-inflammatory metabolite sulfapyridine (derived from sulfasalazine). In human populations, NAT2 enzyme activity exhibits a classic polymorphic distribution, broadly categorizing individuals into rapid, intermediate, or slow acetylators based on their inherited diplotypes.
Clinical Significance and Strength of Evidence
In pharmacogenomic nomenclature established by the Arylamine N-Acetyltransferase Nomenclature Committee and curated by PharmVar, the T allele of rs1799929 is the defining diagnostic tag for the NAT2*5 haplotype cluster. While the standalone SNP rs1799929 does not alter clearance kinetics when uncoupled from functional variants, its strong co-occurrence with non-synonymous mutations makes it a widely utilized proxy for the slow acetylator status. Individuals who carry two slow-acetylating haplotypes clear NAT2 substrate medications more slowly, which has been statistically linked in observational studies to elevated plasma drug concentrations and an increased risk of adverse events, such as isoniazid-induced hepatotoxicity or drug-induced lupus erythematosus. However, evidence directly attributing causal molecular changes to rs1799929 remains limited because the functional deficit is primarily driven by neighboring missense mutations on the same chromosome.
Global Allele Frequencies and Ancestry Differences
The prevalence of the rs1799929 variant demonstrates pronounced divergence across global biogeographical ancestries. In populations of European descent, the minor T allele is relatively common, with an estimated minor allele frequency (MAF) ranging between 0.35 and 0.45. Similar moderate-to-high frequencies are frequently observed in African and South Asian cohorts. Conversely, the T allele is significantly less prevalent in East Asian populations, such as Japanese and Han Chinese cohorts, where the MAF typically falls between 0.05 and 0.10. Consequently, while the NAT2*5 slow acetylator haplotype is one of the most common causes of slow acetylation in European populations, slow acetylators in East Asian populations are more frequently driven by alternate variants, such as the NAT2*6 or NAT2*7 haplotype clusters.
Interpreting Results in Clinical Practice
Genetic testing for rs1799929 provides valuable ancestral and pharmacogenetic context, but an individual SNP cannot provide a definitive clinical phenotype on its own. Accurately determining your overall NAT2 acetylator status requires comprehensive haplotype phasing that accounts for multiple positions across the NAT2 coding region, including rs1801280, rs1799930, and rs1799931. Consumers should never adjust, pause, or initiate prescription medications based solely on commercial raw genetic data. If you are prescribed drugs metabolized by NAT2, such as isoniazid or sulfasalazine, share your concerns and testing reports directly with your prescribing physician or a clinical pharmacogenomics pharmacist to determine whether formal phenotypic or therapeutic drug monitoring is advised.
How common is this variant?
The minor T allele of rs1799929 exhibits an allele frequency of approximately 0.35 to 0.45 in populations of European ancestry, but drops to approximately 0.05 to 0.10 in East Asian populations.
Frequently asked questions
Does having the rs1799929 T allele mean I am definitely a slow acetylator?
Not necessarily. While rs1799929 is strongly linked to the NAT2*5 slow acetylator allele, overall enzyme activity depends on your full diplotype across both copies of your NAT2 gene. If your other chromosome carries a functional rapid allele (such as the reference NAT2*4), you may still have an intermediate or rapid acetylator status.
Why is rs1799929 considered a silent mutation?
The change from cytosine to thymine at coding position 481 replaces one leucine codon with an alternate leucine codon (p.Leu161Leu). Because it does not change the amino acid sequence of the final NAT2 protein, it is classified as synonymous or silent.
Can I use this SNP to adjust my prescription medication doses?
No. Single nucleotide variants should never be used on their own to modify drug regimens or dosages. Any pharmacogenetic interpretation requires clinical-grade testing and direct consultation with your treating physician or a licensed pharmacist.
Which common medications are processed by the NAT2 enzyme?
NAT2 metabolizes several widely prescribed aromatic amine and hydrazine drugs. These include isoniazid (used to treat tuberculosis), dapsone (an antimicrobial), hydralazine (a blood pressure medication), and sulfapyridine (a metabolite of sulfasalazine used in autoimmune disorders).
Sources & further reading
Educational information only, last refreshed 9/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1799929?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29