Human NAT1 alleles (haplotypes)

Updated May 2024

*NAT1* Allele (Haplotype)^a,b	Nucleotide Change(s) and rs Identifier(s)	Amino Acid Change(s)	Phenotype^c	References
**NAT14***	Reference	Reference	Reference	1, 23-30
**NAT13***	*c.222C>A** (rs15561)			2, 8, 34
**NAT15***	c.350_351inv (rs72554606) c.497_499inv (rs72554608) *c.11A>G (rs55793712) c.103del* (rs72554612) *c.232del** (rs72554613)	p.Arg117Thr p.Arg166_Glu167delinsThrGln		3
**NAT110***	*c.215T>A (rs1057126) c.222C>A* (rs15561)		Increased activity	1, 5, 6, 8, 9, 18, 23, 24, 26, 31, 36-39
**NAT111A***	c.-344C>T (rs4986988) c.-40A>T (rs4986989) c.445G>A (rs4987076) c.459G>A (rs4986990) c.640T>G (rs4986783) *c.(192_217)del(9)* *c.222C>A** (rs15561)	p.Val149Ile p.Thr153= p.Ser214Ala	Increased activity	4, 8, 30, 31, 36-39
**NAT111B***	c.-344C>T (rs4986988) c.-40A>T (rs4986989) c.445G>A (rs4987076) c.459G>A (rs4986990) c.640T>G (rs4986783) *c.(192_217)del(9)*	p.Val149Ile p.Thr153= p.Ser214Ala	Increased activity	19, 30, 31, 36-39
**NAT111C***	c.-344C>T (rs4986988) c.-40A>T (rs4986989) c.459G>A (rs4986990) c.640T>G (rs4986783) *c.(192_217)del(9)* *c.222C>A** (rs15561)	p.Thr153= p.Ser214Ala	Increased activity	21, 36-39
**NAT114A***	c.560G>A (rs4986782) *c.215T>A (rs1057126) c.222C>A* (rs15561)	p.Arg187Gln	Decreased activity (Lower than NAT14*)	5,6,31
**NAT114B***	c.560G>A (rs4986782)	p.Arg187Gln	Decreased activity (Lower than NAT14*)	6,7,23, 25-30
**NAT115***	c.559C>T (rs5030839)	p.Arg187Ter	No activity (Truncated protein)	5,7,23, 25-30
**NAT116***	*c.216_218dup* *c.222C>A** (rs15561)			8
**NAT117***	c.190C>T (rs56379106)	p.Arg64Trp	Decreased activity (Lower than NAT14*)	9,10,23, 25-30
**NAT118A***	*c.(192_214)del(3)* (rs4646271) *c.215T>A (rs1057126) c.222C>A* (rs15561)			11,18,22
**NAT118B***	*c.(192_214)del(3)* (rs4646271)			12,18,22
**NAT119A***	c.97C>T (rs56318881)	p.Arg33Ter	No activity (Truncated protein)	10,23, 25-30
**NAT119B***	c.97C>T (rs56318881) c.190C>T (rs56379106)	p.Arg33Ter p.Arg64Trp	No activity (Truncated protein)	35
**NAT120***	c.402T>C (rs146727732)	p.Pro134=	Equivalent to NAT14*	10,23, 25-30
**NAT121***	c.613A>G (rs72554609)	p.Met205Val	Equivalent to NAT14*	10,23, 25-30
**NAT122***	c.752A>T (rs56172717)	p.Asp251Val	Decreased activity (Lower than NAT14*)	10,23, 25-31
**NAT123***	c.777T>C (rs4986991)	p.Ser259=	Equivalent to NAT14*	10,23, 25-30
**NAT124***	c.781G>A (rs72554610)	p.Glu261Lys	Equivalent to NAT14*	10,23, 25-30
**NAT125***	c.787A>G (rs72554611)	p.Ile263Val	Equivalent to NAT14*	10,23, 25-30
**NAT126A***	*c.(192_217)ins(3)* *c.222C>A** (rs15561)			13
**NAT126B***	*c.(192_217)ins(3)*			14
**NAT127***	c.21T>G (rs4986992) c.777T>C (rs4986991)	p.Leu7= p.Ser259=	Equivalent to NAT14*	15,23, 25-30
**NAT128***	*c.(192_217)del(6)*			16,20
**NAT129***	*c.215T>A (rs1057126) c.222C>A* (rs15561) *c.152del** (rs8190859)			17,20
**NAT130***	c.445G>A (rs4987076)	p.Val149Ile		35

Footnotes:

(a)Human NAT1 alleles should be written in upper case and italicized. Protein products of the alleles are also upper case but not italicized and the asterisk is omitted and replaced by underscore. For example, the allele NAT1*4 encodes the protein NAT1_4.

(b)The reference gene sequence (allele NAT1*4) is published in Genbank Accession Number AJ307007.1. SNPs should be identified by designating "A" of the ATG translation initiation codon as number 1. SNPs upstream of this site are designated by negative numbers and SNPs downstream of this site are designated by positive numbers.

(c)Phenotype assignments reflect most current research, but are not necessarily consistent across all studies. Phenotypes may vary with organ/tissue and may be dependent upon other endogenous and environmental factors. Evidence exists for heterogeneity within the “decreased activity” phenotype. Although additional SNPs have been identified outside the open reading frame, they will not be named until a functional effect is observed.

For new submissions or enquiries, please contact Dr. Sotiria Boukouvala (sboukouv@mbg.duth.gr).

Literature

[1] Vatsis, K.P. and Weber, W.W. Structural heterogeneity of Caucasian N-acetyltransferase at the NAT1 gene locus. Arch. Biochem. Biophys. 301: 71-76, 1993.

[2] Blum, M., Grant, D.M., McBride, W., Heim, M. and Meyer, U.A. Human arylamine N-acetyltransferase genes: isolation,chromosomal localization, and functional expression. DNA Cell Biol. 9: 193-203, 1990.

[3] Ohsako, S. and Deguchi, T. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. J. Biol. Chem. 265: 4630-4634, 1990.

[4] Doll, M.A., Jiang, W., Deitz, A.C., Rustan, T.D. and Hein, D.W. Identification of a novel allele at the human NAT1 acetyltransferase locus. Biochem. Biophys. Res. Comm. 233: 584-591, 1997.

[5] Hughes, N.C., Janezic, S.A., McQueen, K.L., Jewett, M.A.S., Castranio, T., Bell, D.A. and Grant, D.M. Identification and characterization of variant alleles of human acetyltransferase NAT1 with defective function using p-aminosalicylate as an in vivo and in vitro probe. Pharmacogenetics 8: 55-66, 1998.

[6] Payton, M.A. and Sim, E. Genotyping human arylamine N-acetyltransferase Type 1 (NAT1): The identification of two novel allelic variants. Biochem. Pharmacol. 55: 361-366, 1998.

[7] Hubbard, A., Moyes, C., Wyllie, A.H., Smith, C.A.D. and Harrison, D.J. N-acetyltransferase 1: two polymorphisms in coding sequence identified in colorectal cancer patients. Br. J. Cancer 77: 913-916, 1998.

[8] de Leon, J.H., Vatsis, K.P. and Weber, W.W. Characterization of naturally occurring and recombinant human N-acetyltransferase variants encoded by NAT1*. Mol. Pharmacol. 58: 288-299, 2000.

[9] Butcher, N.J., Ilett, K.F. and Minchin, R. F. Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by C190T and G560A mutations. Pharmacogenetics 8: 67-72, 1998.

[10] Lin, H.J., Probst-Hensch, N.M., Hughes, N.C., Sakamoto, G.T., Louie, A.D., Kau, I.H., Lin, B.K., Lee, D.B., Lin, J., Frankl, H.D., Lee, E.R., Hardy, S., Grant, D.M. and Haile, R.W. Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas. Pharmacogenetics 8: 269-281, 1998.

[11] Deitz, A.C., Doll, M.A., Fretland, A.J. and Hein, D.W. Homo sapiens N-acetyltransferase NAT1 (allele NAT1*18A) gene, complete cds. Genbank AF032677, 1997.

[12] Deitz, A.C., Doll, M.A., Fretland, A.J. and Hein, D.W. Homo sapiens N-acetyltransferase NAT1 (allele NAT1*18B) gene, complete cds. Genbank AF032678, 1997.

[13] Deitz, A.C., Fretland, A.J., Leff, M.A. and Hein, D.W. Homo sapiens N-acetyltransferase-1 NAT1 gene (NAT1*26A allele), complete cds. Genbank AF071552, 1998.

[14] Deitz, A.C., Fretland, A.J., Leff, M.A., Doll, M.A. and Hein, D.W. Homo sapiens N-acetyltransferase-1 NAT1 gene, (NAT1*26B allele), complete cds. Genbank AF067408, 1998.

[15] Smelt, V.A., Upton, A., Adjaye, J., Payton, M.A., Boukouvala, S., Johnson, N., Mardon, H.J. and Sim, E. Expression of arylamine N-acetyltransferases in pre-term placentas and in human pre-implantation embryos. Hum. Mol. Gen. 9: 1101-1107, 2000.

[16] Lo-Guidice, J.M., Marez, D., Barat, F., Spire, C., Chevalier, D. and Broly, F. Human N-acetyltransferase 1 (NAT1) gene, NAT1*28 allele. Genbank AF082904, 1999.

[17] Lo-Guidice, J.M., Marez, D., Barat, F., Spire, C., Chevalier, D., and Broly, F. Human N-acetyltransferase 1 (NAT1) gene, NAT1*29 allele. Genbank AF082903, 1999.

[18] Yang, M., Katoh, T., Delongchamp, R., Ozawa, S., Kohshi, K. and Kawamoto, T. Relationship between NAT1 genotype and phenotype in a Japanese population. Pharmacogenetics 10: 225-232, 2000.

[19] Johnson, N., Bell, P., Jonovska, V., Budge, M. and Sim, E. NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant. BMC Medical Genetics 17: 5:6, 2004.

[20] Lo-Guidice, J.M., Allorge, D., Chevalier, D., Debuysere, H., Fazio, F., Lafitte, J.J. and Broly, F. Molecular analysis of the N-acetyltransferase 1 gene (NAT1*) using polymerase chain reaction-restriction fragment-single strand conformation polymorphism assay. Pharmacogenetics 10: 293-300, 2000.

[21] Cascorbi, I., Roots, I. and Brockmoller, J. Homo sapiens arylamine N-acetyltransferase 1 (NAT1) gene, NAT1*11C allele, complete cds. Genbank AF308866, 2000.

[22] Sekine, A., Saito, S., Iida, A., Mitsunobu, Y., Higuchi, S., Harigae, S. and Nakamura Y. Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1, and L1CAM in the Japanese population. J. Hum. Genet. 46: 314-319, 2001.

[23] Badawi, A.F., Bell, D.A., Hirvonen, A. and Kadlubar, F. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res. 55: 5230-5237, 1995.

[24] Bell, D.A., Badawi, A.F., Lang, N.P., Ilett, K.F., Kadlubar, F.F. and Hirvonen, A. Polymorphism in the NAT1 polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue. Cancer Res. 55: 5226-5229, 1995.

[25] Grant, D.M., Hughes, N.C., Janezic, S.A., Goodfellow, G.H., Chen, H.J., Gaedigk, A., Yu, V.L and Grewal, R. Human acetyltransferase polymorphisms. Mutat. Res. 376: 61-70, 1997.

[26] Hein, D.W., McQueen, C.A., Grant, D.M, Goodfellow, G.H., Kadlubar, F.F. and Weber, W.W. Pharmacogenetics of the arylamine N-acetyltransferases: A symposium in honor of Wendell W. Weber. Drug Metab. Dispos. 28: 1425-1432, 2000.

[27] Fretland, A.J., Doll, M.A., Leff, M.A. and Hein, D.W. Functional characterization of nucleotide polymorphisms in the coding region of N-acetyltransferase 1 (NAT1). Pharmacogenetics 11: 511-520, 2001.

[28] Butcher, N.J., Boukouvala, S., Sim, E. and Minchin, R.F. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J. 2: 30-42, 2002.

[29] Hein, D.W. Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mut. Res. 506-507: 65-77, 2002.

[30] Zhu, Y. and Hein, D.W. Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1. Pharmacogenomics J. 8: 339-48, 2008.

[31] Vaziri, S.A.J., Hughes, N.C., Sampson, H., Darlington, G., Jewett, M.A.S. and Grant, D.M. Variation in enzymes of arylamine pro-carcinogen biotransformation among bladder cancer patients and control subjects. Pharmacogenetics 11: 7-20, 2001.

[32] Boukouvala, R and Fakis, G. Arylamine N-acetyltransferases: What we learn from genes and genomes. Drug Metab. Rev. 37: 511-564, 2005.

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[34] Zhu, Y., States, J.C., Wang, Y. and Hein, D.W. Functional effects of genetic polymorphisms in the N-acetyltransferase 1 coding and 3’ untranslated regions. Birth Defects Res. (Pt A): Clin. Mol. Teratol. 91: 77-84, 2011.

[35] Agundez, J. (Computationally reconstructed haplotypes from sequencing analysis – unpublished)

[36] Wang, D., Para, M.F., Koletar, S.L. and Sadee W. Human N-acetyltransferase 1 *10 and *11 alleles increase protein expression through distinct mechanisms and associate with sulfamethoxazole-induced hypersensitivity. Pharmacogenet Genomics 21:652-64, 2011.

[37] Millner, L.M., Doll, M.A., Stepp, M.W., States, J.C. and Hein, D.W. Functional analysis of arylamine N-acetyltransferase 1 (NAT1) NAT1*10 haplotypes in a complete NATb mRNA construct. Carcinogenesis 33:348-355, 2012.

[38] Mascarenhas, R., Pietrzak, M., Smith, R.M., Webb, A., Wang, D., Papp, A.C., et al. Allele-selective transcriptome recruitment to polysomes primed for translation: Protein-coding and noncoding RNAs, and RNA isoforms. PLoS One 10:e0136798, 2015.

[39] Hein, D.W., Fakis, G., Boukouvala, S. Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a mini review. Pharmacogenet. Genomics 28:238-244, 2018.