NAT1 (Arylamine N-acetyltransferase 1) variants and mutations
NAT1 (also known as Arylamine N-acetyltransferase 1) is a human protein-coding gene encoding an arylamine N-acetyltransferase 1 protein. It acetylates aromatic amines and related xenobiotics and participates in metabolism of selected endogenous substrates. Genetic variation can alter activity and exposure to some chemicals, although clinical pharmacogenomic effects are generally less established than for NAT2. This analysis covers 717 NAT1 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes attention deficit-hyperactivity disorder, major depressive disorder, and depressive disorder. Example NAT1 variants include M1?, D2G, and D2Y.
Variant analysis overview
- Gene: NAT1
- Protein: Arylamine N-acetyltransferase 1
- UniProt accession: P18440
- Organism: Homo sapiens
- Variants analyzed: 717
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 447 unspecified-consequence records; 98 synonymous variants; 142 missense variants; 13 frameshift variants; 11 stop-gained variants; 2 in-frame deletions; 1 protein altering variant; 2 in-frame insertions; 1 substitution
- Prediction scores: 564 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: attention deficit-hyperactivity disorder, major depressive disorder, depressive disorder, fibromyalgia, Nasal congestion, seasonal allergic rhinitis, obesity disorder, common cold, Pain, Obesity, neuropathic pain, Cough.
Protein structure and variant hotspots
- Protein features: 5 binding sites; 1 post-translational modification sites.
- PTM context: 1 variants overlap post-translational modification 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 NAT1 variants
Examples include M1?, D2G, D2Y, I3L, I3N, I3V, I3M, I3I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10885, cosmic curated COSV56985
- D2G (p.Asp2Gly), gnomAD rs1182777627, REVEL 0.29, CADD 23.90
- D2Y (p.Asp2Tyr), Ensembl rs1805355656
- I3L (p.Ile3Leu), TOPMed rs868623536, gnomAD rs868623536, REVEL 0.04, CADD 16.20
- I3N (p.Ile3Asn), TOPMed rs1805356611
- I3V (p.Ile3Val), TOPMed rs868623536, gnomAD rs868623536, REVEL 0.04, CADD 15.00
- I3M (p.Ile3Met), gnomAD 8-18222056-T-G, REVEL 0.16, CADD 22.70
- I3I (p.Ile3Ile), rs780645147, gnomAD 8-18222056-T-C, CADD 7.44
- E4K (p.Glu4Lys), Ensembl rs781442786
- A5E (p.Ala5Glu), TOPMed rs1372783672
- A5V (p.Ala5Val), gnomAD 8-18216922-C-T, CADD 13.20
- A5A (p.Ala5Ala), gnomAD 8-18216923-A-G, CADD 1.74
- A5S (p.Ala5Ser), gnomAD 8-18216945-G-T, CADD 8.96
- A5G (p.Ala5Gly), rs1365699848, gnomAD 8-18216946-C-G, CADD 10.80
- Y6H (p.Tyr6His), gnomAD 8-18222063-T-C, REVEL 0.36, CADD 24.00
- Y6C (p.Tyr6Cys), gnomAD 8-18222064-A-G, REVEL 0.44, CADD 24.00
- Y6Y (p.Tyr6Tyr), rs1805358080, gnomAD 8-18222065-T-C, CADD 5.54
- L7R (p.Leu7Arg), cosmic curated COSV10885
- L7L (p.Leu7Leu), gnomAD 8-18216897-C-T, CADD 0.87
- L7F (p.Leu7Phe), rs760196826, gnomAD 8-18216902-A-T, CADD 8.49
- L7S (p.Leu7Ser), gnomAD 8-18216904-T-C, CADD 14.20
- L7P (p.Leu7Pro), rs1372282266, gnomAD 8-18216924-G-GC, CADD 13.10
- E8R (p.Glu8Arg), gnomAD 8-18216916-AG-A, CADD 14.90
- E8K (p.Glu8Lys), rs902682517, gnomAD 8-18216918-G-A, CADD 12.20
- E8D (p.Glu8Asp), gnomAD 8-18216920-G-T, CADD 5.08
- E8E (p.Glu8Glu), rs1174532358, gnomAD 8-18216920-G-A, CADD 0.62
- E8G (p.Glu8Gly), rs1053948527, gnomAD 8-18216931-A-G, CADD 14.50
- R9I (p.Arg9Ile), rs772568722, NCI-TCGA Cosmic COSV1044, NCI-TCGA Cosmic COSV5698, cosmic curated COSV56984, REVEL 0.38, CADD 24.80, Variant assessed as somatic; moderate impact.
- R9K (p.Arg9Lys), cosmic curated COSV10441
- I10N (p.Ile10Asn), ExAC rs762718093, TOPMed rs762718093, gnomAD rs762718093, REVEL 0.35, CADD 22.60
- I10T (p.Ile10Thr), ExAC rs762718093, TOPMed rs762718093, gnomAD rs762718093, REVEL 0.30, CADD 22.00
- G11R (p.Gly11Arg), rs1804734452, gnomAD 8-18216939-G-C, CADD 0.82
- G11D (p.Gly11Asp), rs1431158531, gnomAD 8-18216940-G-A, CADD 2.60
- G11C (p.Gly11Cys), gnomAD 8-18216951-G-T, CADD 13.80
- G11A (p.Gly11Ala), rs764988941, gnomAD 8-18216952-G-C, CADD 5.85
- G11G (p.Gly11Gly), rs777973183, gnomAD 8-18216953-C-G, CADD 1.16
- Y12C (p.Tyr12Cys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, Ensembl rs1805360504, REVEL 0.20, CADD 22.30, Variant assessed as somatic; moderate impact.
- Y12D (p.Tyr12Asp), gnomAD 8-18216954-T-G, CADD 13.80
- Y12S (p.Tyr12Ser), rs574170756, gnomAD 8-18216955-A-C, CADD 8.29
- Y12Y (p.Tyr12Tyr), rs1017240061, gnomAD 8-18216956-T-C, CADD 0.80
- K13Q (p.Lys13Gln), gnomAD 8-18216915-A-C, CADD 11.10
- K13E (p.Lys13Glu), gnomAD 8-18216915-A-G, CADD 12.70
- K13R (p.Lys13Arg), gnomAD 8-18216916-A-G, CADD 12.70
- K14K (p.Lys14Lys), gnomAD 8-18222089-G-A, CADD 1.14
- S15I (p.Ser15Ile), gnomAD 8-18216961-G-T, CADD 10.80
- S15S (p.Ser15Ser), rs1192562582, gnomAD 8-18216974-T-C, CADD 1.67
- S15F (p.Ser15Phe), gnomAD 8-18216991-C-T, CADD 13.00
- S15Y (p.Ser15Tyr), gnomAD 8-18219437-C-A, CADD 14.80
- S15V (p.Ser15Val), gnomAD 8-18222086-G-GA, CADD 21.60
- S15C (p.Ser15Cys), gnomAD 8-18222091-C-G, REVEL 0.03, CADD 16.80
- R16S (p.Arg16Ser), ExAC rs770525399, TOPMed rs770525399, gnomAD rs770525399, REVEL 0.01, CADD 3.23
- R16R (p.Arg16Arg), gnomAD 8-18222095-G-A, CADD 1.03
- N17K (p.Asn17Lys), TOPMed rs1563197095, REVEL 0.04, CADD 5.38
- N17S (p.Asn17Ser), Ensembl rs1563197084, REVEL 0.09, CADD 1.30
- N17N (p.Asn17Asn), rs779970548, gnomAD 8-18216959-T-C, CADD 1.39
- K18Q (p.Lys18Gln), TOPMed rs1047363919
- K18S (p.Lys18Ser), rs1469938508, gnomAD 8-18219426-GA-G, CADD 22.40
- K18E (p.Lys18Glu), gnomAD 8-18219427-A-G, CADD 18.10
- K18K (p.Lys18Lys), gnomAD 8-18219429-G-A, CADD 2.40
- K18N (p.Lys18Asn), rs1160764723, gnomAD 8-18222098-CA-C, CADD 21.20
- L19W (p.Leu19Trp), Ensembl rs2117438141
- L19L (p.Leu19Leu), rs774165767, gnomAD 8-18222102-T-C, CADD 1.32
- L19V (p.Leu19Val), gnomAD 8-18222102-T-G, REVEL 0.04, CADD 1.10
- L19M (p.Leu19Met), gnomAD 8-18222102-T-A, REVEL 0.08, CADD 3.38
- D20N (p.Asp20Asn), cosmic curated COSV56985
- D20V (p.Asp20Val), TOPMed rs1456672837, gnomAD rs1456672837, REVEL 0.45, CADD 23.40
- D20Y (p.Asp20Tyr), cosmic curated COSV10732, ExAC rs759261556, TOPMed rs759261556, gnomAD rs759261556, REVEL 0.41, CADD 23.40
- L21V (p.Leu21Val), ExAC rs767455795, gnomAD rs767455795, REVEL 0.19, CADD 20.30
- L21L (p.Leu21Leu), gnomAD 8-18222110-G-A, CADD 5.66
- E22A (p.Glu22Ala), Ensembl rs1805364531, REVEL 0.07, CADD 17.10
- E22K (p.Glu22Lys), gnomAD rs1318508898, REVEL 0.12, CADD 20.30
- E22Q (p.Glu22Gln), gnomAD 8-18222111-G-C, REVEL 0.07, CADD 14.80
- T23A (p.Thr23Ala), cosmic curated COSV56985, ExAC rs767121351, TOPMed rs767121351, gnomAD rs767121351, REVEL 0.14, CADD 23.20
- T23I (p.Thr23Ile), gnomAD 8-18222115-C-T, REVEL 0.15, CADD 23.00
- T23T (p.Thr23Thr), rs149335741, gnomAD 8-18222116-A-G, CADD 7.24
- L24* (p.Leu24Ter), TOPMed rs1805365763
- L24F (p.Leu24Phe), TOPMed rs1805366049, gnomAD rs1805366049, REVEL 0.34, CADD 23.30
- L24I (p.Leu24Ile), gnomAD 8-18216963-C-A, CADD 8.28
- L24L (p.Leu24Leu), gnomAD 8-18216965-A-G, CADD 0.87
- L24N (p.Leu24Asn), rs1805365489, gnomAD 8-18222115-CAT-C, CADD 22.50
- T25I (p.Thr25Ile), rs1051864487, gnomAD 8-18219455-C-T, CADD 9.18
- D29del (p.Asp29del), gnomAD 8-18216973-CTGA-C, CADD 2.91
- D26G (p.Asp26Gly), rs888912240, gnomAD 8-18216976-A-G, CADD 14.00
- D26N (p.Asp26Asn), rs997225921, gnomAD 8-18216978-G-A, CADD 14.10
- D26E (p.Asp26Glu), rs944543056, gnomAD 8-18216980-T-A, CADD 10.20
- D26V (p.Asp26Val), gnomAD 8-18222124-A-T, REVEL 0.08, CADD 16.40
- I27F (p.Ile27Phe), gnomAD 8-18222126-A-T, REVEL 0.25, CADD 22.30
- I27L (p.Ile27Leu), gnomAD 8-18222126-A-C, REVEL 0.14, CADD 17.40
- L28F (p.Leu28Phe), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, Variant assessed as somatic; moderate impact.
- L28I (p.Leu28Ile), ExAC rs764281519, gnomAD rs764281519
- L28R (p.Leu28Arg), TOPMed rs1805367381, REVEL 0.23, CADD 23.00
- Q29* (p.Gln29Ter), rs753610741, gnomAD 8-18216936-C-T, CADD 33.00
- Q29R (p.Gln29Arg), gnomAD 8-18216937-A-G, CADD 3.49
- Q29Q (p.Gln29Gln), gnomAD 8-18216938-G-A, CADD 0.28
- Q29K (p.Gln29Lys), gnomAD 8-18222132-C-A, REVEL 0.10, CADD 9.69
- H30L (p.His30Leu), TOPMed rs1455332072, CADD 5.04
- H30N (p.His30Asn), TOPMed rs867938850, gnomAD rs867938850, CADD 0.76, Uncertain significance, not specified
- H30Y (p.His30Tyr), TOPMed rs867938850, gnomAD rs867938850, REVEL 0.18, CADD 17.80, Uncertain significance
- H30Q (p.His30Gln), rs2117386066, gnomAD 8-18216914-C-G, CADD 3.75
- H30M (p.His30Met), rs1804739573, gnomAD 8-18216982-AC-A, CADD 14.80
- H30H (p.His30His), rs747743180, gnomAD 8-18216983-C-T, CADD 0.32
- H30R (p.His30Arg), rs1156346173, gnomAD 8-18216985-A-G, CADD 2.27
- H30D (p.His30Asp), gnomAD 8-18222135-C-G, REVEL 0.20, CADD 22.40
- Q31R (p.Gln31Arg), ESP rs369130089, ExAC rs369130089, gnomAD rs369130089
- Q31E (p.Gln31Glu), rs935821553, gnomAD 8-18219415-C-G, CADD 4.88
- Q31L (p.Gln31Leu), gnomAD 8-18219416-A-T, CADD 12.90
- Q31H (p.Gln31His), rs1488220730, gnomAD 8-18219417-A-C, CADD 9.67
- Q31K (p.Gln31Lys), rs1250507012, gnomAD 8-18219430-C-A, CADD 10.80
- Q31Q (p.Gln31Gln), gnomAD 8-18219432-G-A, CADD 1.25
- Q31* (p.Gln31Ter), rs1235637580, gnomAD 8-18219433-C-T, CADD 33.00
- I32F (p.Ile32Phe), ExAC rs757584542, TOPMed rs757584542, gnomAD rs757584542, REVEL 0.14, CADD 19.30
- I32L (p.Ile32Leu), ExAC rs757584542, TOPMed rs757584542, gnomAD rs757584542, REVEL 0.09, CADD 13.90
- I32V (p.Ile32Val), ExAC rs757584542, TOPMed rs757584542, gnomAD rs757584542, REVEL 0.06, CADD 13.70
- I32T (p.Ile32Thr), rs1274761447, gnomAD 8-18219413-T-C, CADD 9.07
- I32N (p.Ile32Asn), gnomAD 8-18219413-T-A, CADD 11.90
- I32I (p.Ile32Ile), gnomAD 8-18222143-C-A, CADD 4.77
- R33* (p.Arg33Ter), cosmic curated COSV56985, ExAC rs56318881, TOPMed rs56318881, gnomAD rs56318881, CADD 33.00
- R33Q (p.Arg33Gln), ExAC rs111848753, TOPMed rs111848753, gnomAD rs111848753, REVEL 0.05, CADD 16.70
- R33G (p.Arg33Gly), gnomAD 8-18219421-A-G, CADD 19.40
- R33K (p.Arg33Lys), rs764899326, gnomAD 8-18219422-G-A, CADD 14.10
- R33R (p.Arg33Arg), rs750185765, gnomAD 8-18219423-G-A, CADD 5.78
- R33L (p.Arg33Leu), gnomAD 8-18222145-G-T, REVEL 0.10, CADD 14.00
- A34D (p.Ala34Asp), TOPMed rs1805370130, gnomAD rs1805370130, REVEL 0.13, CADD 22.70
- A34S (p.Ala34Ser), ExAC rs758889084, gnomAD rs758889084
- A34T (p.Ala34Thr), rs1039532946, gnomAD 8-18219418-G-A, CADD 14.20
- A34A (p.Ala34Ala), gnomAD 8-18219420-C-T, CADD 7.73
- V35F (p.Val35Phe), Ensembl rs1805370425
- V35I (p.Val35Ile), rs1156538580, gnomAD 8-18216948-G-A, CADD 0.24
- V35A (p.Val35Ala), rs1221173266, gnomAD 8-18216949-T-C, CADD 1.41
- V35V (p.Val35Val), rs946664455, gnomAD 8-18216971-C-G, CADD 0.38
- P36A (p.Pro36Ala), gnomAD rs1231619198, REVEL 0.32, CADD 22.50
- P36L (p.Pro36Leu), cosmic curated COSV56985, Ensembl rs1805371398
- P36S (p.Pro36Ser), cosmic curated COSV10732, REVEL 0.35, CADD 22.80
- P36Q (p.Pro36Gln), rs756902161, gnomAD 8-18216943-C-A, CADD 10.50
- P36P (p.Pro36Pro), gnomAD 8-18216944-A-C, CADD 1.19
- P36T (p.Pro36Thr), rs1008397809, gnomAD 8-18219466-C-A, CADD 9.44
- P36R (p.Pro36Arg), rs1164987197, gnomAD 8-18219467-C-G, CADD 10.20
- F37L (p.Phe37Leu), rs1188317428, gnomAD 8-18219442-T-C, CADD 22.50
- E38D (p.Glu38Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E38Q (p.Glu38Gln), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, Variant assessed as somatic; moderate impact.
- N39K (p.Asn39Lys), rs1241106979, ClinGen CA370444569, ClinVar RCV004283027, gnomAD rs1241106979, REVEL 0.30, CADD 22.80, Uncertain significance, not specified
- N39N (p.Asn39Asn), rs1241106979, gnomAD 8-18222164-C-T, CADD 6.06
- L40R (p.Leu40Arg), Ensembl rs1805372357
- L40V (p.Leu40Val), gnomAD 8-18222165-C-G, REVEL 0.28, CADD 22.50
- N41D (p.Asn41Asp), ExAC rs780275360, gnomAD rs780275360, REVEL 0.14, CADD 17.00
- N41H (p.Asn41His), ExAC rs780275360, gnomAD rs780275360
- N41Y (p.Asn41Tyr), gnomAD 8-18222168-A-T, REVEL 0.17, CADD 23.50
- N41N (p.Asn41Asn), rs1290315481, gnomAD 8-18222170-C-T, CADD 6.75
- I42T (p.Ile42Thr), gnomAD rs1355361339, REVEL 0.25, CADD 23.80
- I42I (p.Ile42Ile), gnomAD 8-18219450-T-C, CADD 4.46
- H43N (p.His43Asn), ExAC rs747595397, TOPMed rs747595397, gnomAD rs747595397, REVEL 0.33, CADD 23.10
- H43Y (p.His43Tyr), cosmic curated COSV10885, ExAC rs747595397, TOPMed rs747595397, gnomAD rs747595397, REVEL 0.32, CADD 23.10
- H43H (p.His43His), rs1316245583, gnomAD 8-18222176-T-C, CADD 4.58
- C44Y (p.Cys44Tyr), TOPMed rs1805373965, REVEL 0.25, CADD 23.10
- G45A (p.Gly45Ala), TOPMed rs1236531495
- G45R (p.Gly45Arg), 1000Genomes rs181298696, TOPMed rs181298696, gnomAD rs181298696, REVEL 0.29, CADD 24.00
- G45V (p.Gly45Val), cosmic curated COSV10030, TOPMed rs1236531495, REVEL 0.20, CADD 23.40
- G45W (p.Gly45Trp), 1000Genomes rs181298696, TOPMed rs181298696, gnomAD rs181298696
- G45* (p.Gly45Ter), gnomAD 8-18216993-G-T, CADD 33.00
- G45G (p.Gly45Gly), rs1275254501, gnomAD 8-18222182-G-A, CADD 5.34
- D46N (p.Asp46Asn), TOPMed rs1805374923, gnomAD rs1805374923, REVEL 0.08, CADD 20.70
- A47V (p.Ala47Val), gnomAD 8-18222187-C-T, REVEL 0.05, CADD 14.60
- A47A (p.Ala47Ala), rs1805375187, gnomAD 8-18222188-C-T, CADD 4.55
- M48I (p.Met48Ile), cosmic curated COSV56984, ExAC rs769023535, gnomAD rs769023535, REVEL 0.14, CADD 3.22
- M48T (p.Met48Thr), Ensembl rs1563197427
- M48R (p.Met48Arg), gnomAD 8-18222190-T-G, REVEL 0.15, CADD 22.70
- D49N (p.Asp49Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D49Y (p.Asp49Tyr), Ensembl rs2117439650, REVEL 0.04, CADD 17.70
- D49A (p.Asp49Ala), rs1397542565, gnomAD 8-18219461-A-C, CADD 9.37
- D49G (p.Asp49Gly), rs1397542565, gnomAD 8-18219461-A-G, CADD 5.82
- D49V (p.Asp49Val), rs1397542565, gnomAD 8-18219461-A-T, CADD 9.34
- D49D (p.Asp49Asp), rs1413946329, gnomAD 8-18219462-T-C, CADD 3.05
- L50L (p.Leu50Leu), rs1369072680, gnomAD 8-18222195-T-C, CADD 2.36
- G51D (p.Gly51Asp), TOPMed rs1805376891
- L52I (p.Leu52Ile), ExAC rs777369440, TOPMed rs777369440, gnomAD rs777369440
- L52S (p.Leu52Ser), rs754881386, gnomAD 8-18219479-T-C, CADD 14.60
- L52L (p.Leu52Leu), rs572968162, gnomAD 8-18219480-A-G, CADD 0.58
- L52* (p.Leu52Ter), gnomAD 8-18222202-T-G, CADD 34.00
- E53G (p.Glu53Gly), Ensembl rs1563197469, REVEL 0.12, CADD 21.70
- E53K (p.Glu53Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public NAT1 analysis runs
- NAT1 analysis run — NAT1 (717 variants) — completed 2026-08-18