NAT1

Chr 8

N-acetyltransferase 1

Also known as: AAC1, MNAT, NAT-1, NATI

NCBI Gene: 9ENSG00000171428UniProt: P23975

The protein encoded by this gene is an arylamine N-acetyltransferase that catalyzes the transfer of acetyl groups from acetyl-CoA to arylamine and hydrazine substrates, functioning in drug metabolism and folate catabolism. There appears to be conflicting information in the provided data sources regarding the protein function, with one source describing acetylation activity and another describing neurotransmitter transport. The extremely low pLI score indicates this gene is not intolerant to loss-of-function mutations, suggesting it may not be associated with severe developmental disorders.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProtOrthostatic intolerance
0
Active trials
20
Pubs (1 yr)
79
P/LP submissions
0%
P/LP missense
1.89
LOEUF
DN
Mechanism· predicted
Clinical Summary— NAT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
79 unique Pathogenic / Likely Pathogenic· 49 VUS of 145 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.000
Z-score -1.33
OE 1.40 (0.96–1.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.11 (0.98–1.25)
196 obs / 177.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.40 (0.96–1.89)
0≤0.351.4
Missense OE1.11 (0.98–1.25)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 18 / 12.9Missense obs/exp: 196 / 177.3Syn Z: -1.14
DN
0.6162th %ile
GOF
0.5758th %ile
LOF
0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic4
VUS49
Likely Benign4
Benign2
75
Pathogenic
4
Likely Pathogenic
49
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
75
0
75
Likely Pathogenic
0
0
4
0
4
VUS
0
36
13
0
49
Likely Benign
0
1
3
0
4
Benign
0
2
0
0
2
Total039950134

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NAT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients