NAT1

Summary

NAT1 (N-acetyltransferase 1, HGNC:7645) is a protein-coding gene on chromosome 8p22, encoding Arylamine N-acetyltransferase 1 (P18440). Participates in the detoxification of a plethora of hydrazine and arylamine drugs.

This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_000662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7645
Approved symbol	NAT1
Name	N-acetyltransferase 1
Location	8p22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171428
Ensembl biotype	protein_coding
OMIM	108345
Entrez	9

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000307719, ENST00000517441, ENST00000517492, ENST00000517574, ENST00000518029, ENST00000519006, ENST00000520546, ENST00000545197, ENST00000903000, ENST00000903001, ENST00000903002, ENST00000903003, ENST00000903004, ENST00000903005, ENST00000903006, ENST00000903007, ENST00000903008, ENST00000903009, ENST00000938747, ENST00000938748, ENST00000938749

RefSeq mRNA: 10 — MANE Select: NM_000662 NM_000662, NM_001160170, NM_001160171, NM_001160172, NM_001160173, NM_001160174, NM_001160175, NM_001160176, NM_001160179, NM_001291962

CCDS: CCDS55205, CCDS6007

Canonical transcript exons

ENST00000307719 — 3 exons

Exon	Start	End
ENSE00001308408	18222042	18223689
ENSE00002276990	18210109	18210180
ENSE00003642832	18219411	18219489

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.8699 / max 51.3915, expressed in 971 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87568	2.3685	1282
87569	1.8070	960
87566	0.0524	17
87567	0.0104	6

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.26	gold quality
epithelium of bronchus	UBERON:0002031	96.66	gold quality
bronchus	UBERON:0002185	95.60	gold quality
ileal mucosa	UBERON:0000331	94.44	gold quality
colonic mucosa	UBERON:0000317	94.16	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.72	gold quality
epithelium of nasopharynx	UBERON:0001951	93.17	gold quality
nasopharynx	UBERON:0001728	93.15	gold quality
nasal cavity epithelium	UBERON:0005384	91.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.40	gold quality
jejunal mucosa	UBERON:0000399	90.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.77	gold quality
mucosa of transverse colon	UBERON:0004991	89.67	gold quality
palpebral conjunctiva	UBERON:0001812	88.90	gold quality
nasal cavity mucosa	UBERON:0001826	88.28	gold quality
corpus epididymis	UBERON:0004359	88.02	gold quality
endometrium epithelium	UBERON:0004811	87.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.07	gold quality
rectum	UBERON:0001052	86.05	gold quality
pancreatic ductal cell	CL:0002079	85.12	gold quality
nephron tubule	UBERON:0001231	84.43	gold quality
esophagus squamous epithelium	UBERON:0006920	84.17	gold quality
duodenum	UBERON:0002114	84.04	gold quality
right lobe of liver	UBERON:0001114	82.70	gold quality
germinal epithelium of ovary	UBERON:0001304	82.46	gold quality
amniotic fluid	UBERON:0000173	82.26	gold quality
liver	UBERON:0002107	81.15	gold quality
caput epididymis	UBERON:0004358	81.03	gold quality
renal glomerulus	UBERON:0000074	80.49	gold quality
kidney epithelium	UBERON:0004819	79.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, FOS, HSF1, JUN, NR1I2, NR1I3, NR3C1, YY1

miRNA regulators (miRDB)

73 targeting NAT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• Heart tube patterning in Drosophila requires integration of axial and segmental information provided by the Bithorax Complex genes and hedgehog signaling. (PMID:12223408)
• The analysis of these mutations has allowed us to define a new infraabdominal-8 regulatory region, located 5’ to the Abdominal-B transcription unit, and has helped to characterize better the complex regulation of the Abdominal-B gene. (PMID:12399311)
• The promoter targeting sequence (PTS) from the Abdominal-B locus of the bithorax complex facilitates the activity of a distantly located enhancer in transgenic embryos and it restricts the enhancer to a single promoter. (PMID:12490558)
• Data report the mapping of binding sites for ultrabithorax, Abd-A and Abd-B on polytene chromosomes in the Drospohila fat body. (PMID:12835385)
• the Fab-7 boundary contains separable regions that function at different stages of development (PMID:15329342)
• Abd-B acts at multiple levels to regulate gonad development and is a conserved factor in establishing gonad sexual dimorphism in diverse species. (PMID:15454263)
• certain mutations in Abd-B can be rescued in trans by the other copy of the gene in the genetic phenomenon known as transvection (PMID:15572134)
• The relationship between Abd-B and abd-A in the female genital disc is opposite to that of the embryonic epidermis, and contravenes the rule that posteriorly expressed Hox genes downregulate more anterior ones. (PMID:16319117)
• Abdominal-B Hox protein directly activates expression of the yellow pigmentation gene in posterior segments (PMID:16814723)
• Regulatory regons seems to control specifically the level of Abd-B expression in only one parasegment of the bithorax. (PMID:16818450)
• Abdominal-B induces the expression of four intermediate signaling molecules and transcription factors; this expression results in the mosaic activation of several realizator genes during the organogenesis of the external respiratory organ of the larva. (PMID:17113384)
• Enhancer interference limits the interaction of the Abdominal-B promoter to the enhancer(s) from only one regulatory domain in a specific abdominal segment. (PMID:17307884)
• the enhancer blocking capability of the Fab-8 insulator in stably transfected Drosophila S2 cells and show this activity depends on the Fab-8 CTCF binding sites (PMID:17825318)
• Fab-7 and Fab-8 boundaries effectively interact with the upstream region of the Abd-B promoter (PMID:18426914)
• development of the dorsal histoblast nests that will give rise to the adult epithelium is impaired in the posterior segments which identity is specified by Abdominal-B (PMID:18667003)
• Using gene conversion, we exchanged the Fab-7 and Fab-8 boundaries within the BX-C. (PMID:18987027)
• Studies indicate that interaction of Abdominal-B (ABD-B) with dorso ventral and intrasegmental positional information leads to the local activation of ABD-B primary targets in the dorsal region of the eighth abdominal segment (A8). (PMID:19247941)
• The promoter targeting sequences (PTS) from Abd-B locus overcome the enhancer blocking effect of insulators and facilitate long-range enhancer-promoter interactions in transgenic flies (PMID:20045684)
• Results suggest that the expression of cas is segment-specifically regulated negatively by Ubx and abdA genes, but positively by the AbdB gene. (PMID:20563987)
• Data show that the bithorax complex is an approximately 330kb genomic region that is responsible for directing the transcription of three homeotic (Hox) genes Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) during embryonic development. (PMID:21821017)
• By functionally dissecting the Abd-B protein, new features of Abd-B dependent target gene regulation were detected. (PMID:22005458)
• Dsx is a transcriptional target of Abdominal-B, and its regulation sculpts sex-specific abdomen morphology. (PMID:22488883)
• We also found that Abd-B expression in the secondary cells contributes to glycosylation of at least three accessory gland proteins: ovulin (Acp26Aa), CG1656, and CG1652 (PMID:23555301)
• Abdominal-B and caudal inhibit the formation of specific neuroblasts in the Drosophila tail region. (PMID:23903193)
• ABD-B binds more strongly to oligonucleotides containing two 5’-TTAT-3’ canonical core motifs than the probe containing the 5’-TTAC-3’ motif. (PMID:24219869)
• Abd-B provides cues for integrin localization, critical for stem cell positioning. (PMID:24480643)
• Abd-B is required in neurons during development for females to become highly receptive to male courtship. Abd-B neurons control pausing, a key aspect of female sexual receptivity, in response to male courtship. (PMID:24998527)
• We also observed that these functions of abd-A are required in its exclusive as well as the coexpression domain with that of Abd-B (PMID:25340649)
• analysis of blocking and bypass activities of the Fab-8 boundary in the Drosophila bithorax complex (PMID:27428541)
• Data report that the repression of Abd-B, in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages. (PMID:28698559)
• iab-7 polycomb response element (PRE) functions as a component of the Fab-7 boundary. The boundary activity of the iab-7 PRE sequence depends upon a complex called the LBC, LBC is a multiprotein complex that contains at least three distinct DNA binding proteins, the GAGA factor (GAF), Clamp, and Mod(mdg4). (PMID:30110328)
• complete reconstitution of bypass and blocking functions (PMID:31209019)
• The capacity of Abdominal-B to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner (PMID:31371379)
• Redundant enhancers in the iab-5 domain cooperatively activate Abd-B in the A5 and A6 abdominal segments of Drosophila. (PMID:34473267)
• The Drosophila Fab-7 boundary modulates Abd-B gene activity by guiding an inversion of collinear chromatin organization and alternate promoter use. (PMID:36640345)
• Boundary bypass activity in the abdominal-B region of the Drosophila bithorax complex is position dependent and regulated. (PMID:37582404)
• the formation of the buried hydrophobic stacks is critical for the correct folding of the parallel beta-helix, triple-stranded beta-helix, and beta-prism domains in the tailspike protein. (PMID:15322277)
• These results underscore the importance of the TSP C-terminus in the assembly of the mature trimer and demonstrate its potential utility as a model to study the folding and assembly of the TSP C-terminus in isolation. (PMID:19196242)
• TSP morphology controls viral DNA release. (PMID:22364412)
• Crystal structure of the tailspike protein and its interdomain linker (PMID:24816102)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:101040	ENSDARG00000005176
danio_rerio	si:dkey-78a14.4	ENSDARG00000036066
mus_musculus	Nat1	ENSMUSG00000025588
mus_musculus	Nat2	ENSMUSG00000051147
mus_musculus	Nat3	ENSMUSG00000056426
rattus_norvegicus	Nat3	ENSRNOG00000029977
rattus_norvegicus	Nat2	ENSRNOG00000049498
rattus_norvegicus	Nat3	ENSRNOG00000074135

Paralogs (1): NAT2 (ENSG00000156006)

Protein

Protein identifiers

Arylamine N-acetyltransferase 1 — P18440 (reviewed: P18440)

Alternative names: Arylamide acetylase 1, Monomorphic arylamine N-acetyltransferase, N-acetyltransferase type 1

All UniProt accessions (2): F5H5R8, P18440

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.

Subcellular location. Cytoplasm.

Polymorphism. N-acetylation polymorphism is determined by a low or high NAT activity in liver and has been implicated in the action and toxicity of amine-containing drugs. Slow acetylation genotypes have been associated with significant lung cancer risk. Candidate risk factor for susceptibility to neural tube defects. The NAT1*10 allele has been associated with increased risk of colon and urinary bladder cancers and with higher levels of N-acetyltransferase activity and DNA adducts in aromatic amine tumor target organs such as colon and urinary bladder.

Miscellaneous. NAT1 was historically considered to be monomorphic in nature but reports of allelic variations at the NAT1 locus suggest that it is a polymorphically expressed enzyme.

Similarity. Belongs to the arylamine N-acetyltransferase family.

RefSeq proteins (10): NP_000653, NP_001153642, NP_001153643, NP_001153644, NP_001153645, NP_001153646, NP_001153647, NP_001153648, NP_001153651, NP_001278891 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001447	Arylamine_N-AcTrfase	Family
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR053710	Arylamine_NAT_domain_sf	Homologous_superfamily

Pfam: PF00797

Enzyme classification (BRENDA):

• EC 2.3.1.5 — arylamine N-acetyltransferase (BRENDA: 76 organisms, 504 substrates, 242 inhibitors, 322 Km, 150 kcat entries)

Substrate kinetics (BRENDA)

91 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-AMINOFLUORENE	0.0002–5.8	50
ACETYL-COA	0.0084–560	23
5-AMINOSALICYLIC ACID	0.0067–1.7	16
ISONIAZID	0.18–102	14
P-AMINOBENZOIC ACID	0.0028–152	13
SULFAMETHAZINE	0.02–5.39	11
4-NITROPHENYL ACETATE	0.164–10	9
HYDRALAZINE	0.0134–1.327	9
4-AMINOSALICYLATE	0.0941–3.827	8
4-AMINOSALICYLIC ACID	0.258–2.2	8
4-AMINOBENZOIC ACID	0.049–166	7
5-AMINOSALICYLATE	0.2–0.662	7
4-AMINOBIPHENYL	0.0058–1.57	5
P-AMINOSALICYLIC ACID	0.059–5.39	5
4-AMINOBENZOATE	0.052–2.42	4

Catalyzed reactions (Rhea), 1 shown:

• an arylamine + acetyl-CoA = an N-acetylarylamine + CoA (RHEA:16613)

UniProt features (47 total): strand 13, sequence variant 11, helix 11, binding site 5, active site 3, chain 1, mutagenesis site 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2IJA	X-RAY DIFFRACTION	1.7
2PQT	X-RAY DIFFRACTION	1.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18440-F1	98.20	0.99

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 68 (acyl-thioester intermediate); 107; 122

Ligand- & substrate-binding residues (5): 103; 104; 106–107; 208; 214

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (1):

Position	Phenotype
64	reduced enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156582	Acetylation
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-9748784	Drug ADME

MSigDB gene sets: 168 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_BIOLOGICAL_OXIDATIONS, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, BROWNE_HCMV_INFECTION_16HR_UP, PUJANA_CHEK2_PCC_NETWORK, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, SMID_BREAST_CANCER_LUMINAL_B_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, RIGGINS_TAMOXIFEN_RESISTANCE_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, XU_GH1_AUTOCRINE_TARGETS_DN

GO Biological Process (1): xenobiotic metabolic process (GO:0006805)

GO Molecular Function (5): arylamine N-acetyltransferase activity (GO:0004060), protein binding (GO:0005515), acetyltransferase activity (GO:0016407), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Drug ADME	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
N-acetyltransferase activity	1
binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAT1	AADAC	P22760	827
NAT1	GATD3	P0DPI2	813
NAT1	MNAT1	P51948	776
NAT1	PNOC	Q13519	767
NAT1	ESCO1	Q5FWF5	733
NAT1	ESCO2	Q56NI9	730
NAT1	NAA15	Q9BXJ9	714
NAT1	PSCA	O43653	673
NAT1	CYP2E1	P05181	671
NAT1	NAA10	P41227	645
NAT1	CHRNA2	Q15822	609
NAT1	AANAT	Q16613	602
NAT1	NAT14	Q8WUY8	572
NAT1	MUC6	Q6W4X9	551
NAT1	ASMT	P46597	549

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NAT1	ICAM1	psi-mi:“MI:0915”(physical association)	0.590
NAT1	MRRF	psi-mi:“MI:0914”(association)	0.350
LRRK2	SF3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): ICAM1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), NAT1 (Affinity Capture-MS), NAT1 (Synthetic Lethality), NAT1 (Affinity Capture-RNA), ICAM1 (Affinity Capture-MS), SBDS (Affinity Capture-MS), FTO (Affinity Capture-MS), MRRF (Affinity Capture-MS), NAT1 (Protein-peptide)

ESM2 similar proteins: A0A179H324, A0A1B4XBK1, A0A1Y1C7Q5, A0A286LEZ6, A0A346RP51, A0A397HQ89, A0A8F4PN06, A8C7S0, B2DFU4, B7SP66, C9K1M7, C9K7B8, D4AK46, D4D447, G0LET6, G0LET9, I1R9B1, K3UFY2, K3VCL0, M1W268, O62696, O74516, O93801, P0CI62, P0DPA8, P0DUL5, P11245, P11246, P18440, P18605, P40483, P41929, P46580, P50292, P50293, P50294, P50295, P50296, P50297, P50298

Diamond homologs: O62696, P11245, P11246, P12275, P13913, P13914, P18440, P18605, P50292, P50293, P50294, P50295, P50296, P50297, P50298, Q00267, Q1JPA6, Q7YRG5, O52547, O86309, P0A5L9, P77567, P9WJI4, P9WJI5, K3VCL0, Q5UPV4, B7SP66, W7NDP8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AR	“up-regulates quantity by expression”	NAT1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017352 (8:18214064 C>T), RS1000052990 (8:18185717 T>C), RS1000082046 (8:18185510 C>G), RS1000095301 (8:18178969 A>G), RS1000149879 (8:18183986 C>G,T), RS1000156393 (8:18214293 C>T), RS1000186130 (8:18203130 C>T), RS1000214 (8:18196089 T>A,C,G), RS1000231859 (8:18209745 T>G), RS1000244606 (8:18196986 G>A), RS1000341374 (8:18205445 T>C), RS1000366935 (8:18194426 C>T), RS1000388552 (8:18174965 C>G,T), RS1000398944 (8:18183763 C>T), RS1000404121 (8:18170471 T>A,C)

Disease associations

OMIM: gene MIM:108345 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003542_5	Night sleep phenotypes	3.000000e-06
GCST007017_17	Serum bilirubin levels x Mediterranean diet adherence interaction in metabolic syndrome	2.000000e-06
GCST009391_585	Metabolite levels	3.000000e-06
GCST012490_388	Femur bone mineral density x serum urate levels interaction	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0008111	diet measurement
EFO:0010501	indole-3-propionate measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5101 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13253389	Metabolism/PK	3	cotinine

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs15561	NAT1		0.00	0
rs1057126	NAT1		0.00	0
rs4986783	NAT1		0.00	0
rs4986988	NAT1		0.00	0
rs4986989	NAT1		0.00	0
rs4986990	NAT1		0.00	0
rs4987076	NAT1		0.00	0
rs13253389	NAT1	3	2.00	1	cotinine

ChEMBL bioactivities

28 potent at pChembl≥5 of 40 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.92	IC50	120	nM	CHEMBL3262086
6.86	IC50	138	nM	CHEMBL458614
6.48	IC50	330	nM	CHEMBL458614
6.27	IC50	540	nM	CHEMBL3262085
6.22	IC50	600	nM	CHEMBL457919
6.05	IC50	900	nM	CHEMBL3262049
5.96	IC50	1100	nM	CHEMBL2047717
5.96	IC50	1100	nM	CHEMBL431550
5.96	IC50	1100	nM	CHEMBL511165
5.77	IC50	1700	nM	CHEMBL1568345
5.72	IC50	1900	nM	CHEMBL3262055
5.58	IC50	2600	nM	CHEMBL3262084
5.55	IC50	2800	nM	CHEMBL3262053
5.47	IC50	3400	nM	CHEMBL506606
5.44	IC50	3600	nM	CHEMBL110470
5.41	IC50	3900	nM	CHEMBL458705
5.39	IC50	4100	nM	CHEMBL3262048
5.38	IC50	4200	nM	CHEMBL3262082
5.33	IC50	4700	nM	CHEMBL201467
5.24	IC50	5800	nM	CHEMBL3262087
5.18	IC50	6600	nM	CHEMBL3262077
5.12	IC50	7600	nM	CHEMBL456849
5.10	IC50	8000	nM	CHEMBL3262056
5.09	IC50	8100	nM	CHEMBL502693
5.08	IC50	8400	nM	CHEMBL3262059
5.02	IC50	9600	nM	CHEMBL3262061
5.00	IC50	1e+04	nM	CHEMBL3262062
5.00	IC50	1e+04	nM	CHEMBL3262073

PubChem BioAssay actives

27 with measured affinity, of 59 total; 26 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(8-amino-3-anilino-1,4-dioxonaphthalen-2-yl)benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	0.1200	uM
(5Z)-5-[(4-hydroxy-3,5-diiodophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346067: Inhibition of NAT1 in human ZR75 cell lysate assessed as acetylation of aryl amine using PABA as substrate	ic50	0.1380	uM
N-[8-amino-3-(3,5-dimethylanilino)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	0.5400	uM
(5Z)-5-[(3-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	0.6000	uM
N-[3-(4-bromoanilino)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	0.9000	uM
(5Z)-5-[(2-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	1.1000	uM
(5Z)-3-amino-5-[(4-hydroxy-3,5-diiodophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	1.1000	uM
N-(3-anilino-1,4-dioxonaphthalen-2-yl)benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	1.7000	uM
N-[3-(4-bromophenoxy)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	1.9000	uM
N-[7-amino-3-(3,5-dimethylanilino)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	2.6000	uM
N-(1,4-dioxo-3-phenoxynaphthalen-2-yl)benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	2.8000	uM
(5Z)-5-[(3,4-dichlorophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	3.4000	uM
(5Z)-5-[(4-hydroxy-3,5-diiodophenyl)methylidene]-1,3-thiazolidine-2,4-dione	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	3.6000	uM
(5Z)-5-[(2-methylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	3.9000	uM
N-[3-(3,5-dimethylanilino)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	4.1000	uM
N-[5-amino-3-(3,5-dimethylanilino)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	4.2000	uM
(5Z)-5-[(4-chlorophenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	4.7000	uM
N-[3-(3,5-dimethylanilino)-1,4-dioxonaphthalen-2-yl]-N-methylbenzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	5.8000	uM
N-[3-(3,5-dimethylanilino)-5-nitro-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	6.6000	uM
(5Z)-5-[(4-hydroxy-3,5-diiodophenyl)methylidene]-3-methyl-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	7.6000	uM
N-[3-(2-chlorophenyl)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	8.0000	uM
(5Z)-5-[(4-phenylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	346066: Inhibition of human recombinant NAT1 assessed as hydrolysis of acetyl coA using PABA as substrate by Ellman’s method	ic50	8.1000	uM
N-[3-(3-formylphenyl)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	8.4000	uM
N-[3-(furan-2-yl)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	9.6000	uM
N-[3-(furan-3-yl)-1,4-dioxonaphthalen-2-yl]benzenesulfonamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	10.0000	uM
N-[3-(3-formylphenyl)-1,4-dioxonaphthalen-2-yl]benzamide	1141283: Inhibition of human NAT1 assessed as rate of free thiol coenzyme A production using arylamine and AcCoA as substrate by Ellman’s method	ic50	10.0000	uM

CTD chemical–gene interactions

119 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-Aminobenzoic Acid	decreases reaction, increases acetylation, increases reaction, affects acetylation, increases metabolic processing	7
Tobacco Smoke Pollution	affects reaction, increases abundance, affects response to substance, affects expression, decreases expression (+1 more)	7
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
4-biphenylamine	affects response to substance, increases response to substance, increases mutagenesis, increases acetylation, increases activity	5
2-aminofluorene	increases acetylation, increases metabolic processing	5
Estradiol	affects cotreatment, increases expression, decreases expression	4
sodium arsenite	increases expression, increases methylation	3
benzidine	increases metabolic processing, affects acetylation, affects response to substance, affects expression, affects mutagenesis (+1 more)	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression	3
Benzo(a)pyrene	affects methylation, increases expression, affects response to substance	3
Hydrogen Peroxide	decreases activity, decreases reaction	3
Aflatoxin B1	affects cotreatment, increases response to substance, decreases methylation, increases expression	3
methylmercuric chloride	decreases expression	2
4-phenylenediamine	decreases activity, decreases expression, increases acetylation	2
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression, affects response to substance	2
2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects acetylation, affects activity, increases metabolic processing	2
3-nitrobenzanthrone	increases activity, affects cotreatment, increases reduction	2
Acetyl Coenzyme A	affects binding, decreases activity, decreases reaction, affects cotreatment, increases activity (+1 more)	2
Aerosols	affects expression, decreases expression	2
Cotinine	affects response to substance, affects abundance, affects reaction, increases abundance	2
Folic Acid	decreases activity, increases acetylation	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
Aminosalicylic Acid	increases acetylation	2
Pentachlorophenol	decreases reaction, increases acetylation, decreases activity	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Toluene 2,4-Diisocyanate	affects response to substance, increases response to substance	2
Cyclosporine	decreases expression	2
Paclitaxel	decreases expression, decreases activity	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2

ChEMBL screening assays

10 unique, capped per target: 7 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3077325	Binding	Inhibition of Homo sapiens (human) arylamine N-acetyltransferase 1	Design, synthesis, and biological evaluation of new 4-thiazolidinone derivatives substituted with benzimidazole ring as potential chemotherapeutic agents — Med Chem Res
CHEMBL3529019	ADMET	Increase in NAT1 enzyme activity in human HeLa cells at 0.5 uM using p-aminobenzoic acid substrate after 24 hrs by HPLC method relative to untreated control	Histone deacetylase inhibitors increase human arylamine N-acetyltransferase-1 expression in human tumor cells. — Drug Metab Dispos

Cellosaurus cell lines

21 cell lines: 12 spontaneously immortalized cell line, 9 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_8558	YG10007	Spontaneously immortalized cell line	Female
CVCL_A2GZ	V79MZh1A2/hNAT1	Spontaneously immortalized cell line	Male
CVCL_A9BA	MDA-MB-231 NAT1 scrambled	Cancer cell line	Female
CVCL_A9BB	MDA-MB-231 NAT1 down	Cancer cell line	Female
CVCL_A9BC	MDA-MB-231 NAT1 up	Cancer cell line	Female
CVCL_A9BD	MDA-MB-231 NAT1+/- 2-12	Cancer cell line	Female
CVCL_A9BE	MDA-MB-231 NAT1-/- 2-19	Cancer cell line	Female
CVCL_A9BF	MDA-MB-231 NAT1-/- 5-50	Cancer cell line	Female
CVCL_D1NY	Abcam K-562 NAT1 KO	Cancer cell line	Female
CVCL_D2KI	Abcam Raji NAT1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.