NAGS (N-acetylglutamate synthase)

Gene

• Entrez ID: 162417
• Gene name: N-acetylglutamate synthase
• Gene symbol: NAGS
• Synonyms (NCBI Gene): AGAS, ARGA
• Chromosome: 17
• Chromosome location: 17q21.31
• 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 cycl

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894604	G>A	Pathogenic	Stop gained, coding sequence variant
rs104894605	T>C	Pathogenic	Intron variant, missense variant, coding sequence variant
rs104894606	T>C,G	Pathogenic	Intron variant, missense variant, coding sequence variant
rs104894607	G>A,C	Pathogenic	Synonymous variant, intron variant, missense variant, coding sequence variant
rs202041339	T>C	Likely-pathogenic	Splice donor variant
rs730880266	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs730880267	A>T	Pathogenic	Splice acceptor variant
rs730880303	->T	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs886042831	C>G,T	Pathogenic	Synonymous variant, coding sequence variant, intron variant, stop gained
rs1064793209	C>G	Likely-pathogenic	Intron variant
rs1597866317	G>A	Likely-pathogenic	Splice donor variant
rs1597866458	G>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT626560	hsa-miR-548c-3p	HITS-CLIP	23824327
MIRT626559	hsa-miR-532-3p	HITS-CLIP	23824327
MIRT626558	hsa-miR-7106-3p	HITS-CLIP	23824327
MIRT626557	hsa-miR-6772-3p	HITS-CLIP	23824327
MIRT626560	hsa-miR-548c-3p	HITS-CLIP	23824327
MIRT626559	hsa-miR-532-3p	HITS-CLIP	23824327
MIRT626558	hsa-miR-7106-3p	HITS-CLIP	23824327
MIRT626557	hsa-miR-6772-3p	HITS-CLIP	23824327
MIRT1173081	hsa-miR-3127-3p	CLIP-seq
MIRT1173082	hsa-miR-3157-5p	CLIP-seq
MIRT1173083	hsa-miR-3943	CLIP-seq
MIRT1173084	hsa-miR-4313	CLIP-seq
MIRT2050130	hsa-miR-4487	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000050	Process	Urea cycle	IEA
GO:0000050	Process	Urea cycle	TAS
GO:0004042	Function	L-glutamate N-acetyltransferase activity	EXP	12459178, 15050968
GO:0004042	Function	L-glutamate N-acetyltransferase activity	IBA
GO:0004042	Function	L-glutamate N-acetyltransferase activity	IDA	7126172, 23894642
GO:0004042	Function	L-glutamate N-acetyltransferase activity	IEA
GO:0004042	Function	L-glutamate N-acetyltransferase activity	TAS	21757002
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	7126172
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IBA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006526	Process	L-arginine biosynthetic process	IBA
GO:0006526	Process	L-arginine biosynthetic process	IEA
GO:0006536	Process	Glutamate metabolic process	IBA
GO:0006536	Process	Glutamate metabolic process	IEA
GO:0006536	Process	Glutamate metabolic process	TAS	21757002
GO:0016740	Function	Transferase activity	IEA
GO:0016746	Function	Acyltransferase activity	IEA
GO:0016747	Function	Acyltransferase activity, transferring groups other than amino-acyl groups	IEA

Other IDs

• MIM: 608300
• HGNC: 17996
• e!Ensembl: ENSG00000161653

Protein

• UniProt ID: Q8N159
• Protein name: N-acetylglutamate synthase, mitochondrial (EC 2.3.1.1) (Amino-acid acetyltransferase) [Cleaved into: N-acetylglutamate synthase long form; N-acetylglutamate synthase short form; N-acetylglutamate synthase conserved domain form]
• Protein function: Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPS1) activity. {ECO:0000269|PubMed:12459178, ECO:0000269|PubMed:23894642, ECO:0000269|PubM
• PDB: 4K30
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04768	NAT	356 → 521	NAT, N-acetyltransferase, of N-acetylglutamate synthase	Family

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in the adult liver, kidney and small intestine. Weakly expressed in the fetal liver, lung, pancreas, placenta, heart and brain tissue. {ECO:0000269|PubMed:12459178, ECO:0000269|PubMed:12754705}.
• Sequence:

  MATALMAVVLRAAAVAPRLRGRGGTGGARRLSCGARRRAARGTSPGRRLSTAWSQPQPPP
  EEYAGADDVSQSPVAEEPSWVPSPRPPVPHESPEPPSGRSLVQRDIQAFLNQCGASPGEA
  RHWLTQFQTCHHSADKPFAVIEVDEEVLKCQQGVSSLAFALAFLQRMDMKPLVVLGLPAP
  TAPSGCLSFWEAKAQLAKSCKVLVDALRHNAAAAVPFFGGGSVLRAAEPAPHASYGGIVS
  VETDLLQWCLESGSIPILCPIGETAARRSVLLDSLEVTASLAKALRPTKIIFLNNTGGLR
  DSSHKVLSNVNLPADLDLVCNAEWVSTKERQQMRLIVDVLSRLPHHSSAVITAASTLLTE
  LFSNKGSGTLFKNAERMLRVRSLDKLDQGRLVDLVNASFGKKLRDDYLASLRPRLHSIYV
  SEGYNAAAILTMEPVLGGTPYLDKFVVSSSRQGQGSGQMLWECLRRDLQTLFWRSRVTNP
  INPWYFKHSDGSFSNKQWIFFWFGLADIRDSYELVNHAKGLPDSFHKPASDPGS

• Sequence length: 534

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hyperammonemia, type III	Likely pathogenic; Pathogenic	rs2143989504, rs2143991359, rs2049060332, rs2143978628, rs748875458, rs2049086224, rs2143971140, rs886507459, rs2143978844, rs1597866458, rs2143989730, rs764150659, rs2143978561, rs2143980093, rs1319006991, rs2143984711, rs1214956593, rs2143985704, rs2143980228, rs2143989613, rs2143978288, rs2049082368, rs730880266, rs104894604, rs730880267, rs730880303, rs121912591, rs104894605, rs104894606, rs104894607, rs764793347, rs2509281618, rs2509277315, rs2509277257, rs2509280209, rs1356073892, rs886042831, rs2509280530, rs2509285182, rs760267963, rs2509277915, rs2049097502, rs1327031845, rs2509285298, rs375079065, rs1163895765, rs2509277864, rs2509281752, rs781031762, rs2509280484, rs2509277230, rs771090802, rs2049089565, rs1256337877, rs1482475314, rs1235142426, rs2509279961, rs2509285208, rs2509283811, rs2509277941, rs2509283908, rs1309298089, rs942089643, rs2509279497, rs2509277154, rs2509281503, rs2509279402, rs1345709988, rs2509283402, rs2509285270, rs2509277469, rs762205848, rs755257734, rs1567941557, rs1597866317, rs1282296585, rs2049059647, rs2049097522, rs2049079486, rs2049106859, rs1011767739, rs761558985, rs2049106256	RCV001376997 RCV001377143 RCV001383088 RCV001381318 RCV001381890 RCV001382749 RCV001533007 RCV001533009 RCV001877136 RCV001888857 RCV002018258 RCV001908739 RCV001953822 RCV001943651 RCV002029168 RCV002000232 RCV001870907 RCV001879478 RCV001909237 RCV001881145 RCV001958340 RCV001956972 RCV000002529 RCV000002530 RCV000002531 RCV000002532 RCV000002533 RCV000002534 RCV000002535 RCV000002536 RCV002584034 RCV002635867 RCV003033257 RCV003062094 RCV003135320 RCV003130985 RCV001859597 RCV003463080 RCV003470283 RCV003470284 RCV003463081 RCV003470285 RCV003463082 RCV003470286 RCV003463083 RCV003463084 RCV003470287 RCV003463085 RCV003470288 RCV003463086 RCV003463087 RCV003463088 RCV003463089 RCV003463090 RCV003463091 RCV003463092 RCV003463093 RCV003470289 RCV003463094 RCV003499054 RCV003499023 RCV003499821 RCV003499932 RCV003604274 RCV003604703 RCV003604886 RCV003605003 RCV003605077 RCV003602573 RCV003817383 RCV004576289 RCV004576290 RCV004576291 RCV004576293 RCV004576294 RCV001851259 RCV000634851 RCV000721983 RCV000801820 RCV003467539 RCV003497913 RCV001055663 RCV001197995 RCV001224354 RCV001217078 RCV001230957 RCV001230958 RCV001246639	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMINO ACID METABOLISM, INBORN ERRORS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Esophageal atresia	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPERAMMONEMIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERAMMONEMIA DUE TO N-ACETYLGLUTAMATE SYNTHASE DEFICIENCY	—	ClinGen, GWAS catalog, Orphanet ClinGen, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NAGS-related disorder	Likely benign; Uncertain significance; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pyloric stenosis	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anxiety	Anxiety Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	HPO_DG			★☆☆☆☆ Found in Text Mining only
Delirium	Delirium	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetic Foot	Diabetic foot	Pubtator	38287255	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperammonemia	Hyperammonemia	Pubtator	21681857, 30337552	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperammonemia due to N-acetylglutamate synthase deficiency	Hyperammonemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperammonemia, type III	Hyperammonemia	CLINGEN_DG	12447942, 12594532, 12754705, 15714518, 22503289, 27037498, 5160402, 6223815		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperammonemia, type III	Hyperammonemia	BEFREE	12594532, 15714518, 15878741, 25787344, 27771289, 30337552		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperammonemia, type III	Hyperammonemia	CLINVAR_DG	12594532		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperammonemia, type III	Hyperammonemia	GENOMICS_ENGLAND_DG	12594532, 27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperammonemia, type III	Hyperammonemia	CTD_human_DG	12594532, 12754705		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperammonemia, type III	Hyperammonemia	UNIPROT_DG	12754705, 15878741, 27037498		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	BEFREE	27771289		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	39868884	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37047726	Associate	★☆☆☆☆ Found in Text Mining only
Lysinuric Protein Intolerance	Lysinuric Protein Intolerance	BEFREE	30285816		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mood swings	Mood swings	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myelodysplasia	Myelodysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Phenylketonurias	Phenylketonuria	BEFREE	29094226		★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Propionic acidemia	Propionic acidemia	BEFREE	31196016		★☆☆☆☆ Found in Text Mining only
Psychotic episodes	Psychosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31391008	Associate	★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	37047726	Stimulate	★☆☆☆☆ Found in Text Mining only