NAT2 (Arylamine N-acetyltransferase 2) variants and mutations
NAT2 (also known as Arylamine N-acetyltransferase 2) is a human protein-coding gene encoding an arylamine N-acetyltransferase 2 protein. It acetylates isoniazid and multiple aromatic amines, with common alleles producing slow, intermediate, or rapid acetylator phenotypes. These differences strongly influence isoniazid exposure and the risks of hepatotoxicity and other treatment-related adverse effects. This analysis covers 800 NAT2 variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes neurodegenerative disease, facial nerve disorder, and vestibular neuronitis. Example NAT2 variants include D2G, D2H, and D2D.
Variant analysis overview
- Gene: NAT2
- Protein: Arylamine N-acetyltransferase 2
- UniProt accession: P11245
- Organism: Homo sapiens
- Variants analyzed: 800
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 448 unspecified-consequence records; 137 synonymous variants; 181 missense variants; 17 frameshift variants; 11 stop-gained variants; 5 in-frame deletions; 1 stop lost
- Prediction scores: 687 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, facial nerve disorder, vestibular neuronitis, alcohol drinking, Abnormality of the skeletal system, hepatocellular carcinoma, breast cancer, breast carcinoma, melanoma, tooth disorder, type 1 diabetes mellitus, colorectal carcinoma.
Protein structure and variant hotspots
- Protein features: 6 binding sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable NAT2 variants
Examples include D2G, D2H, D2D, I3N, I3T, I3V, E4D, E4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D2G (p.Asp2Gly), ExAC rs754150699, gnomAD rs754150699, REVEL 0.19, CADD 26.20
- D2H (p.Asp2His), Ensembl rs1800759597
- D2D (p.Asp2Asp), gnomAD 8-18400009-C-T, CADD 6.21
- I3N (p.Ile3Asn), 1000Genomes rs186884477, ExAC rs186884477, TOPMed rs186884477, gnomAD rs186884477, REVEL 0.22, CADD 25.60
- I3T (p.Ile3Thr), 1000Genomes rs186884477, ExAC rs186884477, TOPMed rs186884477, gnomAD rs186884477, REVEL 0.14, CADD 23.20
- I3V (p.Ile3Val), 1000Genomes rs200893121, REVEL 0.04, CADD 18.80
- E4D (p.Glu4Asp), TOPMed rs1800759788, REVEL 0.04, CADD 17.20
- E4V (p.Glu4Val), NCI-TCGA Cosmic COSV9967, Variant assessed as somatic; moderate impact.
- A5T (p.Ala5Thr), gnomAD 8-18400016-G-A, REVEL 0.13, CADD 23.30
- A5E (p.Ala5Glu), gnomAD 8-18400017-C-A, REVEL 0.06, CADD 13.80
- A5V (p.Ala5Val), gnomAD 8-18400017-C-T, REVEL 0.12, CADD 22.30
- A5A (p.Ala5Ala), gnomAD 8-18400018-A-G, CADD 7.43
- Y6H (p.Tyr6His), gnomAD rs1435840670, REVEL 0.30, CADD 26.30
- Y6Y (p.Tyr6Tyr), gnomAD 8-18400021-T-C, CADD 7.09
- F7Y (p.Phe7Tyr), NCI-TCGA Cosmic COSV5406, Variant assessed as somatic; moderate impact.
- F7L (p.Phe7Leu), gnomAD 8-18400022-T-C, REVEL 0.21, CADD 22.80
- E8* (p.Glu8Ter), gnomAD rs1800759876, CADD 36.00
- E8G (p.Glu8Gly), gnomAD 8-18400026-A-G, REVEL 0.11, CADD 22.00
- R9I (p.Arg9Ile), NCI-TCGA Cosmic COSV5406, Variant assessed as somatic; moderate impact.
- R9K (p.Arg9Lys), NCI-TCGA Cosmic COSV5406, Variant assessed as somatic; moderate impact.
- I10N (p.Ile10Asn), 1000Genomes rs72466456, ESP rs72466456, ExAC rs72466456, TOPMed rs72466456, REVEL 0.29, CADD 25.50
- I10S (p.Ile10Ser), 1000Genomes rs72466456, ESP rs72466456, ExAC rs72466456, TOPMed rs72466456, REVEL 0.34, CADD 25.70
- I10T (p.Ile10Thr), 1000Genomes rs72466456, ESP rs72466456, ExAC rs72466456, TOPMed rs72466456, REVEL 0.23, CADD 24.70
- I10M (p.Ile10Met), gnomAD 8-18400033-T-G, REVEL 0.32, CADD 22.70
- G11V (p.Gly11Val), ExAC rs747536177, gnomAD rs747536177, REVEL 0.25, CADD 23.80
- Y12C (p.Tyr12Cys), ExAC rs755689546, gnomAD rs755689546, REVEL 0.20, CADD 24.20
- Y12S (p.Tyr12Ser), gnomAD 8-18400038-A-C, REVEL 0.18, CADD 24.20
- Y12Y (p.Tyr12Tyr), gnomAD 8-18400039-T-C, CADD 3.30
- K13* (p.Lys13Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K13E (p.Lys13Glu), gnomAD rs1800760093, REVEL 0.02, CADD 10.20
- K13N (p.Lys13Asn), ExAC rs777235619, TOPMed rs777235619, gnomAD rs777235619, REVEL 0.03, CADD 1.37
- K13Q (p.Lys13Gln), gnomAD rs1800760093, REVEL 0.02, CADD 7.74
- K13R (p.Lys13Arg), gnomAD rs1281741349, REVEL 0.02, CADD 9.16
- N14D (p.Asn14Asp), ExAC rs770525419, REVEL 0.06, CADD 4.76
- N14H (p.Asn14His), ExAC rs770525419
- N14K (p.Asn14Lys), ExAC rs774237368, gnomAD rs774237368, REVEL 0.04, CADD 3.44
- S15T (p.Ser15Thr), gnomAD rs1258543620, REVEL 0.05, CADD 0.42
- S15F (p.Ser15Phe), gnomAD 8-18400047-C-T, REVEL 0.08, CADD 7.99
- S15C (p.Ser15Cys), gnomAD 8-18400047-C-G, REVEL 0.07, CADD 14.40
- R16S (p.Arg16Ser), ExAC rs745585836, gnomAD rs745585836, REVEL 0.02, CADD 6.29
- R16T (p.Arg16Thr), TOPMed rs928522570, gnomAD rs928522570, REVEL 0.02, CADD 1.66
- R16G (p.Arg16Gly), gnomAD 8-18400049-A-G, REVEL 0.02, CADD 5.80
- N17K (p.Asn17Lys), 1000Genomes rs201339185, ExAC rs201339185, TOPMed rs201339185, gnomAD rs201339185, REVEL 0.04, CADD 1.57, Uncertain significance, not specified
- K18I (p.Lys18Ile), gnomAD 8-18400056-A-T, REVEL 0.21, CADD 18.50
- L19W (p.Leu19Trp), TOPMed rs1475615331, gnomAD rs1475615331, REVEL 0.10, CADD 18.10
- L19L (p.Leu19Leu), rs934741595, gnomAD 8-18400058-T-C, CADD 0.07
- D20Y (p.Asp20Tyr), rs532310930, ClinGen CA4651541, ClinVar RCV004472262, 1000Genomes rs532310930, REVEL 0.36, CADD 23.70, Uncertain significance, not specified
- D20H (p.Asp20His), gnomAD 8-18400061-G-C, REVEL 0.26, CADD 23.70
- D20D (p.Asp20Asp), rs984174803, gnomAD 8-18400063-C-T, CADD 5.69
- L21* (p.Leu21Ter), ExAC rs760627448, TOPMed rs760627448, gnomAD rs760627448, CADD 36.00
- L21F (p.Leu21Phe), NCI-TCGA Cosmic COSV5406, NCI-TCGA Cosmic COSV9967, Variant assessed as somatic; moderate impact.
- L21S (p.Leu21Ser), gnomAD 8-18400065-T-C, REVEL 0.26, CADD 24.30
- L21L (p.Leu21Leu), rs1425832493, gnomAD 8-18400066-G-A, CADD 5.74
- E22E (p.Glu22Glu), gnomAD 8-18400069-A-G, CADD 8.63
- T23A (p.Thr23Ala), TOPMed rs1464413878
- T23I (p.Thr23Ile), ExAC rs764315394, gnomAD rs764315394, REVEL 0.27, CADD 23.00
- T23P (p.Thr23Pro), TOPMed rs1464413878, REVEL 0.29, CADD 24.30, Uncertain significance, not specified
- T23T (p.Thr23Thr), rs776798810, gnomAD 8-18400072-A-G, CADD 6.40
- L24I (p.Leu24Ile), rs45477599, UniProt VAR 018853, 1000Genomes rs45477599, ESP rs45477599, REVEL 0.33, CADD 19.50, Benign, in allele NAT2*5L
- L24L (p.Leu24Leu), rs45477599, gnomAD 8-18400073-T-C, CADD 4.20
- L24S (p.Leu24Ser), gnomAD 8-18400074-T-C, REVEL 0.36, CADD 24.50
- L24F (p.Leu24Phe), gnomAD 8-18400075-A-T, REVEL 0.36, CADD 23.00
- T25A (p.Thr25Ala), TOPMed rs1204993451
- T25P (p.Thr25Pro), TOPMed rs1204993451
- T25S (p.Thr25Ser), Ensembl rs1800761112, REVEL 0.13, CADD 15.60
- D26A (p.Asp26Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D26N (p.Asp26Asn), gnomAD rs1325562681, REVEL 0.14, CADD 17.60
- D26D (p.Asp26Asp), gnomAD 8-18400081-C-T, CADD 5.59
- I27L (p.Ile27Leu), ExAC rs765487420, gnomAD rs765487420, REVEL 0.12, CADD 20.40
- I27V (p.Ile27Val), gnomAD 8-18400082-A-G, REVEL 0.07, CADD 14.30
- I27I (p.Ile27Ile), rs1443263835, gnomAD 8-18400084-T-C, CADD 8.52
- L28H (p.Leu28His), gnomAD rs1275931651, REVEL 0.11, CADD 18.90
- L28I (p.Leu28Ile), gnomAD 8-18400085-C-A, REVEL 0.17, CADD 18.00
- L28V (p.Leu28Val), gnomAD 8-18400085-C-G, REVEL 0.05, CADD 14.00
- L28P (p.Leu28Pro), gnomAD 8-18400086-T-C, REVEL 0.27, CADD 24.90
- E29D (p.Glu29Asp), NCI-TCGA Cosmic COSV5406, Variant assessed as somatic; moderate impact.
- E29Q (p.Glu29Gln), TOPMed rs1800761418, REVEL 0.04, CADD 10.40
- E29E (p.Glu29Glu), rs1585138676, gnomAD 8-18400090-G-A, CADD 4.57
- H30H (p.His30His), rs1208793402, gnomAD 8-18400093-C-T, CADD 4.25
- Q31E (p.Gln31Glu), gnomAD 8-18400094-C-G, REVEL 0.15, CADD 23.10
- Q31K (p.Gln31Lys), gnomAD 8-18400094-C-A, REVEL 0.29, CADD 23.70
- I32I (p.Ile32Ile), rs750811489, gnomAD 8-18400099-C-T, CADD 3.43
- I32M (p.Ile32Met), gnomAD 8-18400099-C-G, REVEL 0.06, CADD 12.20
- R33Q (p.Arg33Gln), rs138592670, ESP rs138592670, ExAC rs138592670, TOPMed rs138592670, REVEL 0.08, CADD 5.18, Variant assessed as somatic; moderate impact.
- R33W (p.Arg33Trp), ExAC rs763283305, TOPMed rs763283305, gnomAD rs763283305, REVEL 0.16, CADD 19.60
- R33L (p.Arg33Leu), gnomAD 8-18400101-G-T, REVEL 0.10, CADD 6.51
- R33P (p.Arg33Pro), gnomAD 8-18400101-G-C, REVEL 0.22, CADD 17.90
- A34S (p.Ala34Ser), Ensembl rs750399005, REVEL 0.06, CADD 10.50
- A34T (p.Ala34Thr), Ensembl rs750399005
- A34V (p.Ala34Val), Ensembl rs867460835
- V35A (p.Val35Ala), 1000Genomes rs199780526
- V35F (p.Val35Phe), ExAC rs752047953, TOPMed rs752047953, gnomAD rs752047953, REVEL 0.16, CADD 15.80
- V35I (p.Val35Ile), ExAC rs752047953, TOPMed rs752047953, gnomAD rs752047953, REVEL 0.03, CADD 0.11
- V35L (p.Val35Leu), ExAC rs752047953, TOPMed rs752047953, gnomAD rs752047953
- V35D (p.Val35Asp), gnomAD 8-18400106-G-GA, CADD 23.60
- P36A (p.Pro36Ala), ESP rs377338395, ExAC rs377338395, TOPMed rs377338395, gnomAD rs377338395, REVEL 0.34, CADD 23.50
- P36T (p.Pro36Thr), ESP rs377338395, ExAC rs377338395, TOPMed rs377338395, gnomAD rs377338395, REVEL 0.37, CADD 23.70
- P36R (p.Pro36Arg), gnomAD 8-18400110-C-G, REVEL 0.37, CADD 22.90
- F37L (p.Phe37Leu), gnomAD rs1272204007, REVEL 0.28, CADD 24.00
- F37S (p.Phe37Ser), ExAC rs753310036, TOPMed rs753310036, gnomAD rs753310036, REVEL 0.27, CADD 24.60
- F37F (p.Phe37Phe), rs72554615, gnomAD 8-18400114-T-C, CADD 8.26
- E38E (p.Glu38Glu), gnomAD 8-18400117-G-A, CADD 7.39
- N39H (p.Asn39His), gnomAD 8-18400118-A-C, REVEL 0.37, CADD 24.70
- L40P (p.Leu40Pro), Ensembl rs1800762369, REVEL 0.39, CADD 26.00
- N41Y (p.Asn41Tyr), 1000Genomes rs149283608, ESP rs149283608, ExAC rs149283608, TOPMed rs149283608, REVEL 0.17, CADD 22.40
- N41N (p.Asn41Asn), gnomAD 8-18400126-C-T, CADD 3.92
- N41K (p.Asn41Lys), gnomAD 8-18400126-C-A, REVEL 0.19, CADD 19.90
- M42L (p.Met42Leu), TOPMed rs886633825, gnomAD rs886633825, REVEL 0.07, CADD 11.50
- M42T (p.Met42Thr), TOPMed rs1405525958
- M42V (p.Met42Val), TOPMed rs886633825, gnomAD rs886633825, REVEL 0.06, CADD 10.40
- H43P (p.His43Pro), gnomAD rs1175197943, REVEL 0.37, CADD 24.00
- H43Y (p.His43Tyr), gnomAD 8-18400130-C-T, REVEL 0.25, CADD 23.50
- H43R (p.His43Arg), gnomAD 8-18400131-A-G, REVEL 0.32, CADD 23.70
- H43H (p.His43His), rs370796160, gnomAD 8-18400132-T-C, CADD 0.42
- C44G (p.Cys44Gly), TOPMed rs1800762657, gnomAD rs1800762657, REVEL 0.20, CADD 25.00
- C44S (p.Cys44Ser), TOPMed rs1411878664, gnomAD rs1411878664, REVEL 0.20, CADD 23.30
- C44Y (p.Cys44Tyr), gnomAD 8-18400134-G-A, REVEL 0.22, CADD 23.50
- G45E (p.Gly45Glu), ExAC rs771801023, TOPMed rs771801023, gnomAD rs771801023, REVEL 0.14, CADD 22.80
- G45R (p.Gly45Arg), TOPMed rs1800762800, REVEL 0.20, CADD 24.10
- G45V (p.Gly45Val), ExAC rs771801023, TOPMed rs771801023, gnomAD rs771801023, REVEL 0.17, CADD 22.80
- G45G (p.Gly45Gly), gnomAD 8-18400138-G-A, CADD 5.08
- Q46H (p.Gln46His), ExAC rs779874333, gnomAD rs779874333, REVEL 0.03, CADD 15.60
- Q46K (p.Gln46Lys), Ensembl rs866596704, REVEL 0.10, CADD 14.10
- Q46* (p.Gln46Ter), gnomAD 8-18400139-C-T, CADD 36.00
- Q46E (p.Gln46Glu), gnomAD 8-18400139-C-G, REVEL 0.08, CADD 1.69
- Q46Q (p.Gln46Gln), rs779874333, gnomAD 8-18400141-A-G, CADD 2.62
- A47D (p.Ala47Asp), gnomAD rs1463045225, REVEL 0.08, CADD 6.22
- A47V (p.Ala47Val), gnomAD rs1463045225, REVEL 0.06, CADD 7.87
- M48I (p.Met48Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M48V (p.Met48Val), TOPMed rs1165911161, gnomAD rs1165911161, REVEL 0.14, CADD 8.58
- M48L (p.Met48Leu), gnomAD 8-18400145-A-C, REVEL 0.13, CADD 10.30
- M48T (p.Met48Thr), gnomAD 8-18400146-T-C, REVEL 0.18, CADD 18.60
- M48K (p.Met48Lys), gnomAD 8-18400146-T-A, REVEL 0.19, CADD 22.60
- E49K (p.Glu49Lys), TOPMed rs1189346481, gnomAD rs1189346481, REVEL 0.13, CADD 14.10
- E49E (p.Glu49Glu), rs1800763102, gnomAD 8-18400150-G-A, CADD 1.40
- L50M (p.Leu50Met), gnomAD rs111750824, REVEL 0.11, CADD 14.00
- G51C (p.Gly51Cys), Ensembl rs1800763215
- G51V (p.Gly51Val), gnomAD rs72466457, REVEL 0.09, CADD 10.10
- G51* (p.Gly51Ter), rs1324313404, gnomAD 8-18400150-GTTGGG, CADD 24.70
- G51R (p.Gly51Arg), gnomAD 8-18400154-G-C, REVEL 0.14, CADD 20.00
- G51A (p.Gly51Ala), gnomAD 8-18400155-G-C, REVEL 0.04, CADD 3.24
- G51G (p.Gly51Gly), rs527756685, gnomAD 8-18400156-C-A, CADD 0.85
- L52F (p.Leu52Phe), NCI-TCGA Cosmic COSV9967, Variant assessed as somatic; moderate impact.
- L52V (p.Leu52Val), Ensembl rs1800763364
- E53Q (p.Glu53Gln), TOPMed rs1473213000, gnomAD rs1473213000, REVEL 0.07, CADD 3.38
- E53D (p.Glu53Asp), gnomAD 8-18400162-G-C, REVEL 0.03, CADD 7.31
- E53E (p.Glu53Glu), gnomAD 8-18400162-G-A, CADD 1.37
- A54S (p.Ala54Ser), TOPMed rs1800763438
- A54T (p.Ala54Thr), NCI-TCGA Cosmic COSV5406, Variant assessed as somatic; moderate impact.
- A54V (p.Ala54Val), NCI-TCGA Cosmic COSV9967, Variant assessed as somatic; moderate impact.
- I55V (p.Ile55Val), gnomAD 8-18400166-A-G, REVEL 0.03, CADD 0.11
- F56S (p.Phe56Ser), TOPMed rs1800763515, REVEL 0.22, CADD 24.20
- F56L (p.Phe56Leu), rs1351458528, gnomAD 8-18400166-AT-A, CADD 18.70
- D57G (p.Asp57Gly), ExAC rs776854665, gnomAD rs776854665, REVEL 0.19, CADD 23.10
- D57N (p.Asp57Asn), Ensembl rs78003756, REVEL 0.06, CADD 11.90
- D57V (p.Asp57Val), ExAC rs776854665, gnomAD rs776854665
- D57Y (p.Asp57Tyr), rs78003756, Ensembl rs78003756, REVEL 0.20, CADD 22.90, Variant assessed as somatic; moderate impact.
- D57D (p.Asp57Asp), rs761926388, gnomAD 8-18400174-T-C, CADD 4.07
- H58R (p.His58Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I59F (p.Ile59Phe), ESP rs374728016, ExAC rs374728016, TOPMed rs374728016, gnomAD rs374728016, REVEL 0.20, CADD 10.30
- I59N (p.Ile59Asn), rs773371959, ClinGen CA4651565, ClinVar RCV004220398, ExAC rs773371959, REVEL 0.24, CADD 25.40, Uncertain significance, not specified
- I59T (p.Ile59Thr), ExAC rs773371959, gnomAD rs773371959, REVEL 0.26, CADD 24.00, Uncertain significance
- I59V (p.Ile59Val), ESP rs374728016, ExAC rs374728016, TOPMed rs374728016, gnomAD rs374728016, REVEL 0.04, CADD 0.03
- I59I (p.Ile59Ile), rs766704100, gnomAD 8-18400180-T-C, CADD 6.58
- V60L (p.Val60Leu), gnomAD 8-18400181-G-T, REVEL 0.33, CADD 24.20
- R61T (p.Arg61Thr), gnomAD 8-18400185-G-C, REVEL 0.13, CADD 17.30
- R62R (p.Arg62Arg), rs1800763854, gnomAD 8-18400187-A-C, CADD 9.07
- N63S (p.Asn63Ser), ExAC rs779910396, TOPMed rs779910396, gnomAD rs779910396, REVEL 0.11, CADD 15.30, Uncertain significance, not specified
- R64Q (p.Arg64Gln), rs1801279, ClinGen CA114455, ClinVar RCV000000762, ClinVar RCV003924790, REVEL 0.23, CADD 22.90, Likely benign; drug response, Slow acetylator due to N-acetyltransferase enzyme variant; NAT2-related disorder
- R64W (p.Arg64Trp), rs1805158, UniProt VAR 009075, ExAC rs1805158, TOPMed rs1805158, REVEL 0.15, CADD 20.60, Benign, in allele NAT2*19
- R64R (p.Arg64Arg), rs1805158, gnomAD 8-18400193-C-A, CADD 2.16
- R64P (p.Arg64Pro), gnomAD 8-18400194-G-C, REVEL 0.33, CADD 23.00
- G65A (p.Gly65Ala), rs1019316375, ClinGen CA370635363, ClinVar RCV004472226, REVEL 0.52, CADD 23.70, Uncertain significance, not specified
- G65D (p.Gly65Asp), TOPMed rs1019316375, gnomAD rs1019316375, REVEL 0.53, CADD 24.10, Uncertain significance
- G65V (p.Gly65Val), rs1019316375, ClinGen CA173519898, ClinVar RCV004109224, TOPMed rs1019316375, REVEL 0.54, CADD 24.00, Uncertain significance, not specified
- G65C (p.Gly65Cys), gnomAD 8-18400196-G-T, REVEL 0.52, CADD 24.50
- G65S (p.Gly65Ser), gnomAD 8-18400196-G-A, REVEL 0.50, CADD 24.10
- G66E (p.Gly66Glu), NCI-TCGA Cosmic COSV5406, REVEL 0.51, CADD 25.00, Variant assessed as somatic; moderate impact.
- G66R (p.Gly66Arg), gnomAD 8-18400199-G-A, REVEL 0.50, CADD 26.30
- G66G (p.Gly66Gly), rs753361951, gnomAD 8-18400201-G-C, CADD 0.23
Public NAT2 analysis runs
- NAT2 analysis run — NAT2 (800 variants) — completed 2026-08-18