Human NAT2 alleles (haplotypes)

 

 

Updated May 2024

 

IMPORTANT  NOTICE

In March 2024, PharmVar announced the launch of the new NAT2 webpage (https://www.pharmvar.org/gene/NAT2)

As a result, many NAT2 alleles have now been transitioned into the new PharmVar database (https://www.pharmvar.org/) and updated accordingly on PharmGKB (https://www.pharmgkb.org/)

Important changes have been made to NAT2 nomenclature during transition to the new allele definitions on PharmVar:

·      The NAT2 reference allele was changed

The new reference allele is now catalogued as NAT2*1 by PharmVar and corresponds to legacy allele NAT2*12A (GRCh38 RefSeq NG_012246.1).

·      NAT2*4 is no longer considered as the reference allele in genomic studies

The legacy NAT2*4 reference allele of sequence X14672.1 is now considered a variant by PharmVar. Although sequence X14672.1 will no longer be used as a genomic reference, it is still appropriate to use when comparing the enzymatic or structural properties of polymorphic NAT2 proteins.

·      Star alleles have been renamed by PharmVar

·      Not all previously defined star alleles have been transferred to PharmVar

In the case of haplotypes where the available evidence from the literature was deemed insufficient to support confident allele definition, those haplotypes were not transferred to PharmVar, but they will remain here as legacy alleles.

·      The requirements for new allele definition have changed

·      During the course of updating NAT2 nomenclature, the PharmVar NAT2 gene expert panel (https://www.pharmvar.org/expert-panels) has been able to confirm several of the former haplotypes, while also identifying new ones. We encourage submissions of novel haplotypes for star allele definition, as well as for existing definitions to verify them for transition to PharmVar.

 

See PharmVar and PharmGKB announcements for more information

 

 

 

For new submissions of NAT2 alleles, please contact the PharmVar directly (https://www.pharmvar.org/submission)

 

For enquiries regarding transition from the legacy to the new NAT2 nomenclature, or to validate alleles that have not been transitioned to PharmVar yet, please contact the following persons:

 

Chair of the NAT committee: Dr. Sotiria Boukouvala (sboukouv@mbg.duth.gr)

PharmVar Director: Dr. Andrea Gaedigk (agaedigk@pharmvar.org)

 

 

The current page will remain active as a record of the legacy nomenclature used in the literature before, but it will no longer be updated with new NAT2 alleles

 

See the PharmVar page for newly designated NAT2 alleles

 

 

 

 

NAT2 Allele (Haplotype)a,b

Nucleotide Change(s)

and rs Identifiersc

Amino Acid Change(s)

Phenotyped

References

Transitioned to PharmVar?

NAT2*4

Legacy reference allele

 

None

Rapid

1-17

YES

 

 

NAT2*5A

c.341T>C (rs1801280)

c.481C>T (rs1799929)

 

p.Ile114Thr

p.Leu161=

Slow

2, 9, 10, 18, 19

YES

NAT2*5AAf

c.82C>T

c.341T>C (rs1801280)

c.481C>T (rs1799929)

 

p.Leu28Phe

p.Ile114Thr

p.Leu161=

 

62

NO

NAT2*5ABf

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.609G>T (rs45618543)

 

p.Ile114Thr

p.Leu161=

p.Glu203Asp

 

61

NO

NAT2*5B

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Leu161=

p.Lys268Arg

Slow

3, 9-17, 19, 20

YES

NAT2*5BAf

c.33C>A

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Gly11=

p.Ile114Thr

p.Leu161=

p.Lys268Arg

 

62

NO

NAT2*5BBf

c.341T>C (rs1801280)

c.345C>T (rs45532639)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Asp115=

p.Leu161=

p.Lys268Arg

 

 

62

NO

NAT2*5C

c.341T>C (rs1801280)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Lys268Arg

Slow

9, 10, 18, 19, 21, 22

YES

NAT2*5CAf

c.33C>A

c.341T>C (rs1801280)

c.803A>G (rs1208)

 

p.Gly11=

p.Ile114Thr

p.Lys268Arg

 

62

NO

NAT2*5D

c.341T>C (rs1801280)

 

p.Ile114Thr

Slow

12, 15, 17, 23-26

YES

NAT2*5E

c.341T>C (rs1801280)

c.590G>A (rs1799930)

 

p.Ile114Thr

p.Arg197Gln

Slow

23

YES

NAT2*5F

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.759C>T (rs56011192)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Leu161=

p.Val253=

p.Lys268Arg

Slow

27

YES

NAT2*5G

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Lys268Arg

Slow

35, 61, 63

NO

NAT2*5H

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

c.859del

 

p.Ile114Thr

p.Leu161=

p.Lys268Arg

p.Ser287Profs*59

Slow

28

Discontinued

NAT2*5I

c.341T>C (rs1801280)

c.411A>T (rs4986997)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Leu137Phe

p.Leu161=

p.Lys268Arg

Slow

16

NO

NAT2*5Je

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.590G>A (rs1799930)

 

p.Tyr94=

p.Ile114Thr

p.Arg197Gln

Slow

29, 63

NO

NAT2*5K

c.282C>T (rs1041983)

c.341T>C (rs1801280)

 

p.Tyr94=

p.Ile114Thr

 

30

NO

NAT2*5KAf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Ile114Thr

p.Gly286Glu

 

60

NO

NAT2*5L

c.70T>A (rs45477599)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Leu24Ile

p.Ile114Thr

p.Leu161=

p.Lys268Arg

 

30, 31

YES

NAT2*5M

c.341T>C (rs1801280) 

c.481C>T (rs1799929)

c.803A>G (rs1208)

c.838G>A (rs56393504)

 

p.Ile114Thr

p.Leu161=

p.Lys268Arg

p.Val280Met

 

32

NO

NAT2*5N

c.341T>C (rs1801280)

c.472A>C (rs139351995)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Ile158Leu

p.Leu161=

p.Lys268Arg

 

33

YES

NAT2*5O

c.203G>A (rs72466458)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Cys68Tyr

p.Ile114Thr

p.Leu161=

p.Lys268Arg

 

33

YES

NAT2*5P

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.578C>T (rs79050330)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Thr193Met

p.Arg197Gln

p.Lys268Arg

 

34

NO

NAT2*5Qf

c.341T>C (rs1801280)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Arg197Gln

p.Lys268Arg

 

35

NO

NAT2*5Rf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Tyr94=

p.Ile114Thr

p.Arg197Gln

p.Lys268Arg

 

35

NO

NAT2*5Sf

c.341T>C (rs1801280)

c.857G>A (rs1799931)

 

p.Ile114Thr

p.Gly286Glu

 

35

NO

NAT2*5Tf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.803A>G (rs1208)

 

p.Tyr94=

p.Ile114Thr

p.Lys268Arg

 

35, 62

NO

NAT2*5TAf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.803A>G (rs1208)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Ile114Thr

p.Lys268Arg

p.Gly286Glu

 

60

NO

NAT2*5TBf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Lys268Arg p.Gly286Glu

 

61

NO

NAT2*5Uf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Arg197Gln

p.Lys268Arg

 

35

NO

NAT2*5Vf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

 

35

NO

NAT2*5VAf

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Gly286Glu

 

60

NO

NAT2*5Wf

c.341T>C (rs1801280)

c.354T>C (rs146405047)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Asn118=

p.Leu161=

p.Lys268Arg

 

60

YES

NAT2*5Xf

c.341T>C (rs1801280)

c.403C>G (rs12720065)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Leu135Val

p.Leu161=

p.Lys268Arg

 

60

Discontinued

NAT2*5Yf

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.622T>C (rs56387565)

c.803A>G (rs1208)

 

p.Ile114Thr

p.Leu161=

p.Tyr208His

p.Lys268Arg

 

60

NO

NAT2*5Zf

c.191G>A (rs1801279)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

 

p.Arg64Gln

p.Ile114Thr

p.Leu161=

 

60

NO

NAT2*5ZAf

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Tyr94=

p.Ile114Thr

p.Leu161=

p.Lys268Arg

 

61

NO

 

 

NAT2*6A

c.282C>T (rs1041983)

c.590G>A (rs1799930)

 

p.Tyr94=

p.Arg197Gln

Slow

1-3, 9-17, 19, 22

YES

NAT2*6B

c.590G>A (rs1799930)

 

p.Arg197Gln

Slow

12, 15, 17, 19, 24, 25

YES

NAT2*6C

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Tyr94=

p.Arg197Gln

p.Lys268Arg

Slow

24, 25, 30, 36, 63

YES

NAT2*6D

c.111T>C (rs72554615)

c.282C>T (rs1041983)

c.590G>A (rs1799930)

 

p.Phe37=

p.Tyr94=

p.Arg197Gln

Slow

26

YES

NAT2*6E

c.481C>T (rs1799929)

c.590G>A (rs1799930)

 

p.Leu161=

p.Arg197Gln

Slow

37

YES

NAT2*6F

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Arg197Gln

p.Lys268Arg

 

31

NO

NAT2*6G

c.282C>T (rs1041983)

c.518A>G

c.590G>A (rs1799930)

 

p.Tyr94=

p.Lys173Arg

p.Arg197Gln

 

31

NO

NAT2*6H

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.766A>G (rs55700793)

 

p.Tyr94=

p.Arg197Gln

p.Lys256Glu

 

31, 33

YES

NAT2*6I

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.838G>A (rs56393504)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Arg197Gln

p.Val280Met

p.Gly286Glu

 

31

NO

NAT2*6J

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Arg197Gln

p.Gly286Glu

 

32

NO

NAT2*6K

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.638C>T (rs138707146)

 

p.Tyr94=

p.Arg197Gln

p.Pro213Leu

 

32

YES

NAT2*6L

c.282C>T (rs1041983)

c.345C>T (rs45532639)

c.590G>A (rs1799930)

 

p.Tyr94=

p.Asp115=

p.Arg197Gln

 

32

YES

NAT2*6M

c.152G>T (rs72466457)

c.282C>T (rs1041983)

c.590G>A (rs1799930)

 

p.Gly51Val

p.Tyr94=

p.Arg197Gln

 

33

YES

NAT2*6N

c.282C>T (rs1041983)

c.481C>T (rs1799929)

c.590G>A (rs1799930)

 

p.Tyr94=

p.Leu161=

p.Arg197Gln

 

35, 62

NO

NAT2*6Of

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.838G>A (rs56393504)

 

p.Tyr94=

p.Arg197Gln

p.Val280Met

 

39

YES

NAT2*6Pf

c.403C>G (rs12720065)

c.590G>A (rs1799930)

 

p.Leu135Val

p.Arg197Gln

 

40

YES

NAT2*6Qf

c.282C>T (rs1041983)

c.308C>T

c.590G>A (rs1799930)

 

p.Tyr94=

p.Thr103Ile

p.Arg197Gln

 

40

NO

NAT2*6Rf

c.282C>T (rs1041983)

c.481C>T (rs1799929)

c.590G>A (rs1799930)

c.803A>G (rs1208)

 

p.Tyr94=

p.Leu161=

p.Arg197Gln

p.Lys268Arg

 

35

NO

NAT2*6Sf

c.590G>A (rs1799930)

c.857G>A (rs1799931)

 

p.Arg197Gln

p.Gly286Glu

 

35

NO

NAT2*6Tf

c.481C>T (rs1799929)

c.590G>A (rs1799930)

c.857G>A (rs1799931)

 

p.Leu161=

p.Arg197Gln

p.Gly286Glu

 

35

NO

NAT2*6Uf

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.579G>T (rs144176822)

 

p.Tyr94=

p.Arg197Gln

p.Thr193=

 

60

NO

NAT2*6Vf

c.403C>G (rs12720065)

c.590G>A (rs1799930)

c.838G>A (rs56393504)

 

p.Leu135Val

p.Arg197Gln

p.Val280Met

 

60

NO

NAT2*6Wf

c.282C>T (rs1041983)

c.590G>A (rs1799930)

c.803A>G (rs1208)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Arg197Gln

p.Lys268Arg

p.Gly286Glu

 

 

61

NO

 

 

NAT2*7A

c.857G>A (rs1799931)

p.Gly286Glu

Slow; Substrate dependent?

2, 11, 12, 15, 17, 19, 36

YES

NAT2*7B

c.282C>T (rs1041983)

c.857G>A (rs1799931)

p.Tyr94=

p.Gly286Glu

Slow; Substrate dependent?

1, 9-18, 36

YES

NAT2*7C

c.282C>T (rs1041983)

c.803A>G (rs1208)

c.857G>A (rs1799931)

p.Tyr94=

p.Lys268Arg

p.Gly286Glu

 

34, 40

YES

NAT2*7D

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.857G>A (rs1799931)

 

p.Arg64Gln

p.Tyr94=

p.Gly286Glu

 

33

NO

NAT2*7Ef

c.282C>T (rs1041983)

c.481C>T (rs1799929)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Leu161=

p.Gly286Glu

 

39

NO

NAT2*7Ff

c.282C>T (rs1041983)

c.481C>T (rs1799929)

c.803A>G (rs1208)

c.857G>A (rs1799931)

 

p.Tyr94=

p.Leu161=

p.Lys268Arg

p.Gly286Glu

 

35

NO

NAT2*7Gf

c.226T>G

c.282C>T (rs1041983)

c.857G>A (rs1799931)

 

p.Tyr76Asp

p.Tyr94=

p.Gly286Glu

 

59

NO

 

 

NAT2*10

c.499G>A (rs72554617)

p.Glu167Lys

Slow; Substrate dependent?

11, 15-17

YES

 

 

NAT2*11A

c.481C>T (rs1799929)

p.Leu161=

Rapid

12, 15, 17, 41, 63

YES

NAT2*11B

c.481C>T (rs1799929)

c.859del

 

p.Leu161=

p.Ser287Profs*59

 

28

Discontinued

 

 

 

NAT2*12A

c.803A>G (rs1208)

 

p.Lys268Arg

Rapid

12, 15, 17, 19, 42, 43

YES

NAT2*12B

c.282C>T (rs1041983)

c.803A>G (rs1208)

 

p.Tyr94=

p.Lys268Arg

Rapid

9, 10, 19, 25

YES

NAT2*12C

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Leu161=

p.Lys268Arg

Rapid

9, 10, 21, 24, 25, 43

YES

NAT2*12D

c.364G>A (rs4986996)

c.803A>G (rs1208)

 

p.Asp122Asn

p.Lys268Arg

Slow

16

YES

NAT2*12E

c.282C>T (rs1041983)

c.578C>T (rs79050330)

c.803A>G (rs1208)

 

p.Tyr94=

p.Thr193Met

p.Lys268Arg

 

30, 31, 33

YES

NAT2*12F

c.622T>C (rs56387565)

c.803A>G (rs1208)

 

p.Tyr208His

p.Lys268Arg

 

30, 33

YES

NAT2*12G

c.609G>T (rs45618543)

c.803A>G (rs1208)

 

p.Glu203Asp

p.Lys268Arg

 

31

YES

NAT2*12H

c.403C>G (rs12720065)

c.803A>G (rs1208)

 

p.Leu135Val

p.Lys268Arg

 

32

YES

NAT2*12I

c.228C>T (rs72466459)

c.803A>G (rs1208)

 

p.Tyr76=

p.Lys268Arg

 

33

YES

NAT2*12J

c.29C>T (rs72466456)

c.803A>G (rs1208)

 

p.Ile10Thr

p.Lys268Arg

 

33

YES

NAT2*12Kf

c.472A>C (rs139351995)

c.803A>G (rs1208)

 

p.Ile158Leu

p.Lys268Arg

 

40

NO

NAT2*12Lf

c.665T>G

c.803A>G (rs1208)

 

p.Phe222Cys

p.Lys268Arg

 

40

NO

NAT2*12Mf

c.282C>T (rs1041983)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Tyr94=

p.Leu161=

p.Lys268Arg

 

35, 62

NO

NAT2*12Nf

c.121A>T (rs149283608)

c.803A>G (rs1208)

 

p.Asn41Tyr

p.Lys268Arg

 

60

NO

NAT2*12Of

c.29T>C (rs72466456)

c.609G>T (rs45618543)

c.803A>G (rs1208)

 

p.Ile10Thr

p.Glu203Asp

p.Lys268Arg

 

60

NO

NAT2*12Pf

c.472A>C (rs139351995)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Ile158Leu

p.Leu161=

p.Lys268Arg

 

60

NO

NAT2*12Qf

c.33C>A

c.803A>G (rs1208)

 

p.Gly11=

p.Lys268Arg

 

62

NO

NAT2*12Rf

c.518A>G

c.609G>T (rs45618543)

c.803A>G (rs1208)

 

p.Lys173Arg

p.Glu203Asp

p.Lys268Arg

 

62

NO

NAT2*12Sf

c.33C>A

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Gly11=

p.Leu161=

p.Lys268Arg

 

62

NO

 

 

NAT2*13A

c.282C>T (rs1041983)

p.Tyr94=

Rapid

9, 10, 12-15, 17, 19, 22, 23, 43, 44

YES

NAT2*13B

c.282C>T (rs1041983)

c.578C>T (rs79050330)

 

p.Tyr94=

p.Thr193Met

 

31

NO

NAT2*13Cf

c.282C>T (rs1041983)

c.665T>G

 

p.Tyr94=

p.Phe222Cys

 

40

NO

NAT2*13Df

c.282C>T (rs1041983)

c.766A>G (rs55700793)

 

p.Tyr94=

p.Lys256Glu

 

60

NO

NAT2*13Ef

c.282C>T (rs1041983)

c.641C>T

 

p.Tyr94=

p.Thr214Ile

 

60

NO

NAT2*13Ff

c.282C>T (rs1041983)

c.838G>A (rs56393504)

 

p.Tyr94=

p.Val280Met

 

60

NO

NAT2*13Gf

c.282C>T (rs1041983)

c.472A>C (rs139351995)

 

p.Tyr94=

p.Ile158Leu

 

60

NO

NAT2*13Hf

c.33C>A

c.282C>T (rs1041983)

 

p.Gly11=

p.Tyr94=

 

62

NO

 

 

NAT2*14A

c.191G>A (rs1801279)

 

p.Arg64Gln

Slow

9, 10, 12-15, 17, 21, 45

YES

NAT2*14B

c.191G>A (rs1801279)

c.282C>T (rs1041983)

 

p.Arg64Gln

p.Tyr94=

Slow

45, 46

YES

NAT2*14C

c.191G>A (rs1801279)

c.341T>C (rs1801280)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Ile114Thr

p.Leu161=

p.Lys268Arg

Slow

23-25, 33

YES

NAT2*14D

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.590G>A (rs1799930)

 

p.Arg64Gln

p.Tyr94=

p.Arg197Gln

Slow

23, 25, 36

YES

NAT2*14E

c.191G>A (rs1801279)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Lys268Arg

Slow

23, 31, 36

YES

NAT2*14F

c.191G>A (rs1801279)

c.341T>C (rs1801280)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Ile114Thr

p.Lys268Arg

Slow

25

YES

NAT2*14G

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Tyr94=

p.Lys268Arg

Slow

26

YES

NAT2*14H

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.683C>T (rs45518335)

 

p.Arg64Gln

p.Tyr94=

p.Pro228Leu

 

31

YES

NAT2*14I

 

c.191G>A (rs1801279)

c.481C>T (rs1799929)

c.803A>G (rs1208)

 

p.Arg64Gln

p.Leu161=

p.Lys268Arg

 

47

YES

NAT2*14Jf

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.633G>A

 

p.Arg64Gln

p.Tyr94=

p.Thr211=

 

40

NO

NAT2*14Kf

c.191G>A (rs1801279)

c.282C>T (rs1041983)

c.838G>A (rs56393504)

 

p.Arg64Gln

p.Tyr94=

p.Val280Met

 

60

NO

NAT2*14Lf

c.7A>G (rs200893121)

c.191G>A (rs1801279)

c.282C>T (rs1041983)

 

p.Ile3Val

p.Arg64Gln

p.Tyr94=

 

60

NO

 

 

NAT2*17

c.434A>C (rs72554616)

 

p.Gln145Pro

Slow

48

NO

NAT2*18

c.845A>C (rs56054745)

 

p.Lys282Thr

Rapid

48

NO

NAT2*19

c.190C>T (rs1805158)

 

p.Arg64Trp

Slow

49-51

YES

NAT2*20

c.600A>G (rs72466461)

 

p.Glu200=

 

33

YES

NAT2*21

c.458C>T (rs72466460)

 

p.Thr153Ile

 

33

YES

NAT2*22f

c.609G>T (rs45618543)

p.Glu203Asp

 

40

NO

NAT2*23f

c.70T>A (rs45477599)

 

p.Leu24Ile

 

40

NO

NAT2*24f

c.403C>G (rs12720065)

 

p.Leu135Val

 

40

NO

NAT2*25f

c.665T>G

 

p.Phe222Cys

 

40

NO

NAT2*26f

c.809T>C

 

p.Ile270Thr

 

38, 60

NO

NAT2*27f

c.589C>T

 

p.Arg197Ter

 

38, 60

YES

NAT2*28

c.622T>C (rs56387565)

 

p.Tyr208His

 

62

NO

 

Footnotes

 

(a)     Human NAT2 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 NAT2*4 encodes the protein NAT2_4.

(b)     The legacy reference allele sequence (NAT2*4) is published in Genbank Assession Number X14672. NAT2*4 is the most common “rapid” allele globally. However, it is not the most common occurring allele in all populations.

(c)     Signature SNP for each allelic group is shown in red font. 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 [58].

(d)     Phenotype assignments reflect most current research but are not necessarily a consensus of all research papers. Evidence also exists for heterogeneity within the “slow” acetylator phenotype. For comprehensive reviews, see references [52-56]. Although additional SNPs have been identified outside the open reading frame (e.g., see refs [31,32,57]), they will not be named until a functional effect is observed.

(e)        The SNPs on NAT2*5J were determined by RFLP methods which are indirect.

(f)         Haplotypes predicted from genotypes by computational PHASE analysis.

 

 

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

 

Literature

 

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[59]       Verhagen, L.M., Coenen, M.J., López,D., García, J.F., de Waard, J.H., Schijvenaars, M.M., Hermans, P.W. and Aarnoutse, R.E. Full-gene sequencing analysis of NAT2 and its relationship with isoniazid pharmacokinetics in Venezuelan children with tuberculosis. Pharmacogenomics 15:285-96, 2014.

[60]       Podgorná, E., Diallo, I., Vangenot, C., Sanchez-Mazas, A., Sabbagh, A., Černý, V. and Poloni, E.S. Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa. BMC Evol. Biol. 15:263, 2015.

[61]       Zahra, M.A., Kandeel, M., Aldossary, S.A. and Al-Taher, A. Study on genotyping polymorphism and sequencing of N-Acetyltransferase 2 (NAT2) among Al-Ahsa Population. Biomed. Res. Int. 2020:8765347, 2020.

[62]       Lopes, M.Q.P., Teixeira, R.L.F., Cabello, P.H., Nery, J.A.C., Sales, AM., Nahn JR., E.P., Moreira, M.V., Stahlke, E.V.R., Possuelo, L.G., Rossetti, M.L.R., Rabahi, M.F., Silva, L.F.M., Leme, P.A., Woods, W.J., Nobre, M.L., de Oliveira, M.L.W., Narahashi, K., Cavalcanti, M., Suffys, P.N., Boukouvala, S., Gallo, M.E.N. and Santos, A.R. Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas. Front. Pharmacol. 14:1278720, 2023.

[63]       Luca, F., Bubba, G., Basile, M., Brdicka, R., Michalodimitrakis, E., Rickards, O., Vershubsky, G., Quintana-Murci, L., Kozlov, A.I. and Novelletto, A. Multiple advantageous amino acid variants in the NAT2 gene in human populations. PLoS One. 3(9):e3136, 2008.