NAT1
protein-codingN-acetyltransferase 1, the group of Arylamine N-acetyltransferases
Gene summary
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. [provided by RefSeq, Aug 2011]
- AAC1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Biochemical
Intervention: Pharmacogenomic
Rationale: Medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NAT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000662.8. 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 | 1 | 5 | 6 | |||
| missense | 36 | 1 | 1 | 38 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 6 | 1 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000653.3 | 1 | MANE Select | |
| Ensembl | ENSP00000307218.4 | 1 | MANE Select | |
| RefSeq | NP_001153642.1 | 1 | Standard | |
| RefSeq | NP_001153643.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Drug metabolism - other enzymes - Homo sapiens (human)
- Caffeine metabolism - Homo sapiens (human)
- Chemical carcinogenesis - Homo sapiens (human)
- Busulfan Pathway, Pharmacodynamics
- Arylamine metabolism
Biological Process
- xenobiotic metabolic process
Molecular Function
- arylamine N-acetyltransferase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000545197
- Coding exons
- 3
- Length
- 53213
- Individuals with no LoFs
- 125105
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 634
- Defined
- 125742
- p
- 0.00254
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.499 | 196 | 177 | 1.11 | 0.00000854 | 2313 |
| Missense (PolyPhen) | 46 | 41.821 | 1.0999 | 564 | ||
| Synonymous | -1.14 | 78 | 66.2 | 1.18 | 0.00000315 | 662 |
| Loss of Function | -1.33 | 18 | 12.9 | 1.40 | 6.97e-7 | 156 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.0030 | 0.0030 | notable |
| Ashkenazi Jewish | 0.0025 | 0.0025 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0037 | 0.0037 | notable |
| South Asian | 0.00075 | 0.00072 | rare |
| Other | 0.0058 | 0.0057 | notable |
dbNSFP Gene Annotations
Source:
- 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
- 0.0920
Intolerance Scores
- LoFtool
- 0.996
- RVIS EVS
- 0.91
- RVIS percentile EVS
- 89.44
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |