Human NAT alleles/haplotypes

NAT1 alleles

NAT2 alleles


Non-human NAT alleles/haplotypes

NAT1 alleles

NAT2 alleles

NAT3 alleles



The Database of Arylamine N-Acetyltransferases (NATs)


·       Introduction

·       NAT nomenclature

·       The NAT website

·       Literature


Arylamine N-acetyltransferases (NATs, EC are polymorphic enzymes responsible for the inter-individual variability in the effects of arylamine and arylhydrazine drugs and carcinogens in human populations. Humans have two NAT isoenzymes, encoded by polymorphic genes (NAT1 and NAT2) on chromosome 8p22. A third inactive locus, the pseudogene NATP1, is located between NAT1 and NAT2 in humans. Loci homologous to the human NAT genes have been identified in several eukaryotic species (including protists, fungi and animals, but not plants), as well as in prokaryotes (bacteria and archaea). The pharmacogenetic and toxicogenetic significance of NAT is well-established, and there is evidence that the NAT polymorphisms may affect susceptibility to disease, especially cancer. Today, investigators employ the NAT family as a model system to study enzymatic structure and function, gene expression, population genetics, comparative genomics and evolution. NAT has been investigated as a candidate pharmacological target in tuberculous mycobacteria and as a putative biomarker in tumors responsive to steroid hormones. NATs have also been investigated for their functional variability in bacteria and fungi [References 1-35 for selected reviews].


NAT nomenclature

The discovery of numerous polymorphic NAT alleles in human populations and model organisms led to the introduction of a consensus nomenclature for NATs in 1995 [36]. The NAT Gene Nomenclature Committee was formed at the first International NAT Workshop that took place in 1998 (Kuranda, Queensland, Australia) [37]. Nomenclature issues where further discussed during dedicated sessions at the second (Oxford, UK, 2001) [38], third (Vancouver, Canada, 2004), fourth (Alexandroupolis, Greece, 2007) [39], fifth (Paris, France, 2010) [40], sixth (Toronto, Canada, 2013) and seventh (Trier, Germany, 2016) [41] NAT Workshops. The eighth NAT Workshop is scheduled at Columbus (OH, USA) in September 25-26, 2024.


The NAT committee has published two nomenclature updates [42, 43] to advise investigators as to the proper use of symbols for the NAT genes and alleles. General instructions regarding the correct naming of genes are available from the HUGO Gene Nomenclature Committee (HGNC), which has approved NAT as the official gene symbol for arylamine N-acetyltransferase. The basic rules for naming NAT genes and alleles are described in [36, 42-46] and outlined here below:

·       The symbols of NAT genes and alleles in all species except rodents are all uppercase (NAT). In rodents, only the first letter is uppercase, followed by lowercase (Nat). Protein products are always all uppercase (NAT, for rodent species too).

·       Genes and alleles are always italicized (NAT or Nat), while protein products are not (NAT, for rodents and other species).

·       The nomenclature is species-specific. An official organism identification code should precede the gene symbol [e.g. (MOUSE)Nat]. Please ask the manager of this website for appropriate organism identification codes.

·       For the purpose of taxonomic classification, a unique identification number should be provided for each species (e.g. 10090 for Mus musculus), but not incorporated in the gene or allele symbol. Those taxon IDs must be obtained from NCBI’s Taxonomy Database.

·       Arabic numerals placed immediately after the NAT symbol indicate different NAT genes of the same organism [e.g. (RABIT)NAT1 and (RABIT)NAT2 are two distinct (paralogous) genes of the rabbit, encoding for two functionally differentiated isoenzymes].

·       Arabic numerals separated from the gene symbol with an asterisk indicate different alleles of the same NAT gene [e.g. (MACMU)NAT2*1 and (MACMU)NAT2*2 are two polymorphic alleles of the NAT2 gene of the Rhesus macaque and they produce variants of the NAT2 isoenzyme]. The asterisk is replaced by underscore in the non-italicized symbol of the corresponding allozymes [i.e. (MACMU)NAT2_1 and (MACMU)NAT2_2 are the protein variants produced by the polymorphic (MACMU)NAT2*1 and (MACMU)NAT2*2 alleles of the Rhesus NAT2 gene].

·       When more than one NAT locus is discovered in a specific genome, the symbols NAT1, NAT2 etc. should be assigned hierarchically, according to the deduced amino acid identity between each new sequence and a NAT reference sequence. The reference sequences are: the NAT1 protein of Salmonella typhimurium LT2 (accession no. BAA14331) for bacteria, the deduced NAT1 protein of Halogeometricum borinquense, strain DSM 11551 (accession no. BN001449) for archaea, the NAT1 protein of Gibberella moniliformis (accession no. EU552489) for fungi and the NAT1 protein of Homo sapiens (accession no. X17059) for animals. In the case of protists, which constitute a highly divergent domain of eukaryotic life, investigators are encouraged to contact the NAT committee for advice on appropriate reference sequences [44]. For example, a gene of the Rhesus macaque that encodes a protein with 94% identity to human NAT1 is assigned symbol NAT1 and a second gene, whose product is only 82% identical to human NAT1, is assigned symbol NAT2. If functional data is available, those should be taken into account when allocating symbols to new NAT genes, especially if the identity to the reference sequence is not sufficiently informative. For example, rabbit NAT1 and NAT2 are both 75% identical to human NAT1, but studies have demonstrated that rabbit NAT1 and human NAT1 (as well as rabbit NAT2 and human NAT2) are functionally equivalent. The only exception to this rule is the rodents, where the Nat2 gene is functionally more similar to human NAT1 and vice versa. Although confusing, the NAT nomenclature of rodents is widely accepted by scientists in the field and is currently a consensus.

·       In humans, the legacy reference alleles/haplotypes of the NAT1 and NAT2 genes have historically been designated symbols NAT1*4 and NAT2*4. Human haplotypes are commonly grouped into specific allelic groups, based on shared signature SNPs (e.g. all haplotypes belonging to the NAT2*5 allelic group share signature SNP c.341T>C and are classified as NAT2*5A, *5B, *5C etc.). For human SNPs, it is useful to also indicate the official rs” numbers identifying the polymorphism in the dbSNP database (e.g. SNP c.341T>C is identified by rs1801280). However, please note that, from March 2024, this legacy nomenclature has been discontinued for human NAT2 alleles (but not for human NAT1 alleles), as the Pharmacogenetics Variation Consortium (PharmVar) launched a new NAT2 webpage (, with many (but not all) NAT2 alleles now transitioned into the new PharmVar nomenclature system. As a consequence, important changes have been introduced to the legacy NAT2 nomenclature that should be adopted and implemented from now on. The present page will remain active as a record of the legacy NAT2 allele nomenclature used in the literature before, but it will no longer be updated with new NAT2 alleles. New submissions of human NAT2 alleles should be directed to PharmVar (

·       In non-human species, the reference allele of a NAT gene is assigned symbol NAT1*1. This is usually either the wild type allele or the first allele identified for a specific organism. The capital letters used to indicate NAT allelic groups in the humans (e.g. NAT2*5A, *5B, *5C etc.) should not be used in non-human NAT symbols, even if two alleles share common SNPs (e.g. former rat alleles Nat2*21A and Nat2*21B have now been discontinued and replaced by Nat2*2 and Nat2*3).

·       SNPs are not reported for the NAT genes of non-human species, unless they are validated experimentally. Likewise, SNPs identified outside the open reading frame of human or non-human NAT genes (e.g. in the promoter, 5΄-/3΄-untranslated regions or introns) are not reported, unless a functional effect is demonstrated.

·       To add a non-human NAT gene to the database, the sequence of the open reading frame and deduced protein product should be provided, together with the official (latin) name and taxon ID of the species. Additional information, e.g. regarding the position of SNPs or non-coding exons, may also accompany the submission. If available, previous scientific literature relevant to the submitted sequences can be provided.

·       When reporting the position of SNPs, non-coding exons, transcriptional regulatory elements etc. of NAT genes, the A of the ATG translation initiation codon should always be considered as number 1. Upstream positions are designated with negative numbers and downstream positions with positive numbers.

·       Nucleotide and amino acid variation must be reported according to the Human Genome Variation Society (HGVS) nomenclature guidelines and recommendations (e.g. c.590G>A and p.Arg197Gln for the nucleotide and corresponding amino acid substitution, respectively).


Scientists who wish to name new NAT sequences should follow the above rules and contact the manager of this website who will provide official symbols for new NAT genes or alleles. Colleagues are encouraged to request official symbols for NAT sequences prior to their publication in the scientific literature, as well as to submit their gene-specific data to the NAT website (see below), whenever they judge that this information can be made public. Release of gene-specific data on the NAT website does not preclude its submission to central sequence repositories, such as the ENA/GenBank/DDBJ databases, which is encouraged.


The NAT website

An official website, launched and maintained by Dr. D.W. Hein at the University of Louisville, was created by the NAT Gene Nomenclature Committee after the 1998 NAT workshop and contained information relevant to the consensus nomenclature of all NAT genes and alleles in humans and other organisms [37, 42]. At the 2007 NAT workshop, it was agreed that a second website, launched and maintained by Dr. S. Boukouvala at the University of Thrace [39, 43, 45], would be dedicated to the nomenclature of non-human NAT genes. With the number of NAT-homologous genes identified in sequenced prokaryotic and eukaryotic genomes increasing day after day, these databases were intended as a useful resource for investigators who wish to study the genetic, evolutionary and functional diversity of NAT homologues. At the 2010 NAT workshop, it was decided that the two websites would be consolidated into a single website hosted by the University of Thrace and providing annotated information about both human and non-human NAT genes and alleles.


Please direct all requests for new NAT gene or allelic symbols to Dr. S. Boukouvala (, apart from new submissions of human NAT2 alleles which should be directed to PharmVar instead (





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The NAT Gene Nomenclature Committee:

Dr. Sotiria Boukouvala

Department of Molecular Biology & Genetics,

Democritus University of Thrace, Greece.

Prof. David W. Hein

Department of Pharmacology & Toxicology,

University of Louisville, USA.

Prof. Denis M. Grant

Department of Pharmacology & Toxicology,

University of Toronto, Canada.

Prof. Edith Sim

Department of Pharmacology,

University of Oxford, UK.

Prof. Rodney F. Minchin

School of Biomedical Sciences,

University of Queensland, Australia.

Prof. José A.G Agúndez

Department of Pharmacology, Medical School,

University of Extremadura, Spain.


Dr. Fernando Rodrigues-Lima

Laboratory of Molecular and Cellular Responses to Xenobiotics, University Paris Diderot, France.



Created & maintained by:

Dr. Sotiria Boukouvala

Tel.: +30-25510-30632



Special thanks to:

Eirini Vagena

Vasiliki Garefalaki

Georgia Papanikolaou

Maria-Aggeliki Tsatiri

Dimitra Basdani


for help with collection, annotation and presentation of the data



Contact address:

Department of Molecular Biology and Genetics

Democritus University of Thrace, University Campus, Dragana, Building 10, Alexandroupolis, 68100, Greece.

Fax.: +30-25510-30632