NAT2

N-acetyltransferase 2, the group of Arylamine N-acetyltransferases

Basic information

Region (hg38): 8:18391281-18401218

Previous symbols: [ "AAC2" ]

Links

ENSG00000156006 ∙ NCBI:10 ∙ OMIM:612182 ∙ HGNC:7646 ∙ Uniprot:P11245 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acetylation, NAT2-related	AD	Pharmacogenomic	Variants may have pharmacogenomic importance, as medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs	Biochemical	13820968; 14164493; 5414058; 871863; 913027; 7378086; 3707628; 3712391; 3778197; 3815349; 1968463; 2068113; 8102597; 7920692; 7668286; 8637343; 9918135; 9660060; 12654968; 16416399; 19379125; 19891553; 20485159; 20602614; 20860460; 20941486; 22092036

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAT2 gene.

• Inborn genetic diseases (13 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAT2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			12	1	2	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	2	2

Variants in NAT2

This is a list of pathogenic ClinVar variants found in the NAT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-18400061-G-T		not specified	Uncertain significance (Oct 02, 2023)
8-18400179-T-A		not specified	Uncertain significance (Aug 02, 2021)
8-18400194-G-A		Slow acetylator due to N-acetyltransferase enzyme variant • NAT2-related disorder	Likely benign (Jan 13, 2020)
8-18400197-G-C		not specified	Uncertain significance (Sep 20, 2023)
8-18400197-G-T		not specified	Uncertain significance (Sep 15, 2021)
8-18400244-A-G		not specified	Uncertain significance (Jan 26, 2023)
8-18400249-C-T		NAT2-related disorder	Likely benign (Aug 09, 2019)
8-18400250-G-T		not specified	Uncertain significance (Jul 06, 2021)
8-18400260-C-A		not specified	Uncertain significance (Jan 23, 2023)
8-18400285-C-T		NAT2-related disorder	Benign (Mar 29, 2023)
8-18400344-T-C		Slow acetylator due to N-acetyltransferase enzyme variant • NAT2-related disorder	Benign (Dec 29, 2023)
8-18400349-G-A		not specified	Uncertain significance (Jan 31, 2024)
8-18400390-C-T		NAT2-related disorder	Likely benign (Jun 05, 2019)
8-18400409-G-C		not specified	Uncertain significance (Dec 27, 2023)
8-18400470-G-A		not specified	Likely benign (Dec 03, 2021)
8-18400470-G-T		not specified	Uncertain significance (Dec 27, 2023)
8-18400484-C-T		NAT2-related disorder	Benign (Dec 29, 2023)
8-18400507-G-A		NAT2-related disorder	Likely benign (Jan 27, 2022)
8-18400508-T-C		not specified	Uncertain significance (Mar 14, 2023)
8-18400550-A-G		not specified	Uncertain significance (Aug 19, 2023)
8-18400582-G-T			Likely benign (Mar 29, 2018)
8-18400593-G-A		Slow acetylator due to N-acetyltransferase enzyme variant • NAT2-related disorder	Benign (Mar 29, 2023)
8-18400612-G-T			Benign (Aug 20, 2018)
8-18400701-G-C		not specified	Uncertain significance (Feb 17, 2022)
8-18400709-G-C		not specified	Uncertain significance (Nov 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAT2	protein_coding	protein_coding	ENST00000286479	1	9974

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000327	0.200	125701	0	25	125726	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.38	196	149	1.32	0.00000709	1890
Missense in Polyphen		70	49.337	1.4188		645
Synonymous	-0.140	60	58.6	1.02	0.00000308	555
Loss of Function	-0.219	8	7.36	1.09	3.77e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000436	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000615
Middle Eastern	0.000436	0.000435
South Asian	0.000164	0.000163
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Benzodiazepine Pathway, Pharmacokinetics;Drug metabolism - other enzymes - Homo sapiens (human);Caffeine metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Caffeine Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Caffeine and Theobromine metabolism;Arylamine metabolism;Metapathway biotransformation Phase I and II;Acetylation;Phase II - Conjugation of compounds;Biological oxidations;Metabolism (Consensus)

Recessive Scores

• pRec: 0.0915

Intolerance Scores

• loftool: 0.816
• rvis_EVS: 1.84
• rvis_percentile_EVS: 97.09

Haploinsufficiency Scores

• pHI: 0.0266
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.223

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Nat3
• Phenotype: normal phenotype

Gene ontology

• Biological process: xenobiotic metabolic process
• Cellular component: cytosol
• Molecular function: arylamine N-acetyltransferase activity;protein binding