NAT2

protein-coding

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

Gene summary

This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

Previous symbols:

AAC2

MANE transcript

NM_000015.3

Inheritance

AR, AD

ClinVar variants

U:39B:10

Top phenotype

Acetylation, NAT2-related

gnomAD constraint

pLI —, LoF o/e 1.09

Max pathogenic AF

—

Genomic locus

chr8:18,391,282-18,401,218

External References & Databases

Ensembl (ENSG00000156006)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

acetylation, slowLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009472

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Acetylation, NAT2-relatedAD

Manifestation: Biochemical

Intervention: Pharmacogenomic

Rationale: 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

Refs: 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

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAT2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 4

NAT2-related disorderTotal: 4

Slow acetylator due to N-acetyltransferase enzyme variantTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000015.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar		6
missense			39 clinvar	2 clinvar	2 clinvar	43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	8	2	49

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000015.3	RefSeq	NP_000006.2	1	MANE Select
ENST00000286479.4	Ensembl	ENSP00000286479.3	1	MANE Select
ENST00000520116.1	Ensembl	ENSP00000428416.1	1	Standard
ENST00000520116.2	Ensembl	ENSP00000428416.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Benzodiazepine Pathway, Pharmacokinetics
Drug metabolism - other enzymes - Homo sapiens (human)
Caffeine metabolism - Homo sapiens (human)
Chemical carcinogenesis - Homo sapiens (human)
Busulfan Pathway, Pharmacodynamics

Biological Process

xenobiotic metabolic process

Molecular Function

arylamine N-acetyltransferase activity
protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000286479
Coding exons: 1
Length: 9974
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125726
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.38	196	149	1.32	0.00000709	1890
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0915

Intolerance Scores

LoFtool: 0.816
RVIS EVS: 1.84
RVIS percentile EVS: 97.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.223

Gene Damage Prediction

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