NAGS
Chr 17ARN-acetylglutamate synthase
Also known as: AGAS, ARGA
The N-acetylglutamate synthase enzyme catalyzes the formation of N-acetylglutamate from glutamate and acetyl coenzyme-A in the mitochondrial matrix, where N-acetylglutamate serves as an essential cofactor for carbamyl phosphate synthetase I in the urea cycle. Autosomal recessive mutations cause N-acetylglutamate synthase deficiency, resulting in hyperammonemia due to impaired urea cycle function. The pathogenic mechanism involves reduced availability of the N-acetylglutamate cofactor, which decreases carbamyl phosphate synthetase I activity and compromises the body's ability to eliminate ammonia.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 18 | 0 | 7 | 0 | 25 |
Likely Pathogenic | 26 | 5 | 15 | 0 | 46 |
VUS | 0 | 119 | 5 | 5 | 129 |
Likely Benign | 0 | 1 | 74 | 212 | 287 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 7 | |||
| Total | 44 | 125 | 104 | 217 | 497 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NAGS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools