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    NAGS N-acetylglutamate synthase [ Homo sapiens (human) ]

    Gene ID: 162417, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NAGSprovided by HGNC
    Official Full Name
    N-acetylglutamate synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:17996
    See related
    Ensembl:ENSG00000161653 MIM:608300; AllianceGenome:HGNC:17996
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AGAS; ARGA
    Summary
    The N-acetylglutamate synthase gene encodes a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme-A. NAG is a cofactor of carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in mammals. This gene may regulate ureagenesis by altering NAG availability and, thereby, CPSI activity. Deficiencies in N-acetylglutamate synthase have been associated with hyperammonemia. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in duodenum (RPKM 7.8), small intestine (RPKM 6.4) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NAGS in Genome Data Viewer
    Location:
    17q21.31
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (44004622..44009068)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (44857133..44861579)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (42081990..42086436)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene pancreatic polypeptide Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42030343-42030846 Neighboring gene peptide YY Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42082913-42083668 Neighboring gene Sharpr-MPRA regulatory region 11566 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr17:42091474-42092673 Neighboring gene Sharpr-MPRA regulatory region 15580 Neighboring gene transmembrane protein 101 Neighboring gene uncharacterized LOC124904152 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:42102423-42102924

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. A trial with N-carbamylglutamate may not detect all patients with NAGS deficiency and neonatal onset. Nordenström A, et al. J Inherit Metab Dis, 2007 Jun. PMID 17510757
    2. Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene. Häberle J, et al. Hum Mutat, 2021 Dec. PMID 34510628, Free PMC Article
    3. N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Elpeleg O, et al. Ann Neurol, 2002 Dec. PMID 12447942
    4. Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency. Gessler P, et al. Eur J Pediatr, 2010 Feb. PMID 19533169
    5. N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region. Williams M, et al. Sci Rep, 2018 Oct 18. PMID 30337552, Free PMC Article

    See all (37) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
      Title: NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
    2. Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.
      Title: Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.
    3. Variation in the N-acetylglutamate Synthase Enhancer Region is associated with N-Acetylglutamate Synthase Deficiency.
      Title: N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region.
    4. The specificity of the assay was validated by demonstrating a complete deficiency of NAGS in liver homogenates from Nags -/- mice. CONCLUSION: The novel NAGS enzyme assay reported herein can be used for the diagnosis of inherited NAGS deficiency and may also be of value in the study of secondary hyperammonemia present in various inborn errors of metabolism as well as drug treatment.
      Title: A novel UPLC-MS/MS based method to determine the activity of N-acetylglutamate synthase in liver tissue.
    5. Results identified 36 NAGS mutations in NAGSD patients; 61% of which are missense mutations. Phenotypes associated with these mutations in the GNAT domain are more severe than phenotypes of that of amino acid kinase domain. Enzyme activity and stability assays with 12 mutations, together with in silico structural analysis, support the pathogenic role of most NAGSD-associated mutations found.
      Title: Understanding N-Acetyl-L-Glutamate Synthase Deficiency: Mutational Spectrum, Impact of Clinical Mutations on Enzyme Functionality, and Structural Considerations.
    6. Data indicate the formation of alternative N-acylglutamates by N-acetylglutamate synthase (NAGS).
      Title: Inhibition of N-acetylglutamate synthase by various monocarboxylic and dicarboxylic short-chain coenzyme A esters and the production of alternative glutamate esters.
    7. Sp1, CREB, HNF-1, and NF-Y, known to be responsive to hormones and diet, regulate NAGS transcription
      Title: Transcriptional regulation of N-acetylglutamate synthase.
    8. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    10. NAGS deficiency in humans leads to hyperammonemia and can be primary, due to mutations in the NAGS gene or secondary due to other mitochondrial aberrations that interfere with the normal function of the same enzyme.
      Title: N-acetylglutamate synthase: structure, function and defects.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Hyperammonemia, type III
    MedGen: C0268543 OMIM: 237310 GeneReviews: Urea Cycle Disorders Overview
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC133025

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-glutamate N-acetyltransferase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables L-glutamate N-acetyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables L-glutamate N-acetyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables L-glutamate N-acetyltransferase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in L-arginine biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in L-arginine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glutamate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutamate metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in urea cycle TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    N-acetylglutamate synthase, mitochondrial
    Names
    amino-acid acetyltransferase
    NP_694551.1
    XP_011522740.1
    XP_011522741.1
    XP_054171243.1
    XP_054171244.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008106.1 RefSeqGene

      Range
      4959..9405
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_153006.3 → NP_694551.1  N-acetylglutamate synthase, mitochondrial

      See identical proteins and their annotated locations for NP_694551.1

      Status: REVIEWED

      Source sequence(s)
      AC023855, AI241153, AY116538, BF589712
      Consensus CDS
      CCDS11473.1
      UniProtKB/Swiss-Prot
      B2RAZ9, Q8IWR4, Q8N159
      UniProtKB/TrEMBL
      K7EK11
      Related
      ENSP00000293404.2, ENST00000293404.8
      Conserved Domains (2) summary
      cd04236
      Location:102 → 371
      AAK_NAGS-Urea; N-acetylglutamate (NAG) kinase-like domain of the NAG Synthase (NAGS) of the urea cycle found in animals. Ureogenic NAGS is a mitochondrial enzyme catalyzing the formation of NAG from acetylcoenzyme A and L-glutamate; NAG is an essential allosteric ...
      pfam04768
      Location:357 → 520
      NAT; N-acetyltransferase, of N-acetylglutamate synthase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      44004622..44009068
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011524438.2 → XP_011522740.1  N-acetylglutamate synthase, mitochondrial isoform X1

      UniProtKB/TrEMBL
      K7EK11
      Conserved Domains (4) summary
      PRK04531
      Location:115 → 464
      PRK04531; acetylglutamate kinase; Provisional
      cd04236
      Location:102 → 371
      AAK_NAGS-Urea; AAK_NAGS-Urea: N-acetylglutamate (NAG) kinase-like domain of the NAG Synthase (NAGS) of the urea cycle found in animals. Ureogenic NAGS is a mitochondrial enzyme catalyzing the formation of NAG from acetylcoenzyme A and L-glutamate; NAG is an essential ...
      pfam16642
      Location:32 → 93
      KCNQ2_u3; Unstructured region on Potassium channel subunit alpha KvLQT2
      cl14605
      Location:357 → 459
      DUF619-like; DUF619 domain of various N-acetylglutamate Kinases and N-acetylglutamate Synthases

    2. XM_011524439.2 → XP_011522741.1  N-acetylglutamate synthase, mitochondrial isoform X2

      See identical proteins and their annotated locations for XP_011522741.1

      UniProtKB/TrEMBL
      Q2NKP2
      Conserved Domains (2) summary
      cl00452
      Location:1 → 205
      AAK; Amino Acid Kinases (AAK) superfamily, catalytic domain; present in such enzymes like N-acetylglutamate kinase (NAGK), carbamate kinase (CK), aspartokinase (AK), glutamate-5-kinase (G5K) and UMP kinase (UMPK). The AAK superfamily includes kinases that ...
      cl28353
      Location:84 → 359
      PRK05279; N-acetylglutamate synthase; Validated

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      44857133..44861579
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054315268.1 → XP_054171243.1  N-acetylglutamate synthase, mitochondrial isoform X1

      UniProtKB/TrEMBL
      K7EK11

    2. XM_054315269.1 → XP_054171244.1  N-acetylglutamate synthase, mitochondrial isoform X2

      UniProtKB/TrEMBL
      Q2NKP2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N159.1 GenPept UniProtKB/Swiss-Prot:Q8N159

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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