NADSYN1 (NAD synthetase 1)

Gene

• Entrez ID: 55191
• Gene name: NAD synthetase 1
• Gene symbol: NADSYN1
• Synonyms (NCBI Gene): VCRL3
• Chromosome: 11
• Chromosome location: 11q13.4
• Summary: Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT647702	hsa-miR-6819-3p	HITS-CLIP	23824327
MIRT647700	hsa-miR-6877-3p	HITS-CLIP	23824327
MIRT647699	hsa-miR-6849-3p	HITS-CLIP	23824327
MIRT647698	hsa-miR-2682-3p	HITS-CLIP	23824327
MIRT647697	hsa-miR-6781-3p	HITS-CLIP	23824327
MIRT647696	hsa-miR-4320	HITS-CLIP	23824327
MIRT647695	hsa-miR-6512-3p	HITS-CLIP	23824327
MIRT647694	hsa-miR-6720-5p	HITS-CLIP	23824327
MIRT647693	hsa-miR-33a-5p	HITS-CLIP	23824327
MIRT647692	hsa-miR-33b-5p	HITS-CLIP	23824327
MIRT647691	hsa-miR-4503	HITS-CLIP	23824327
MIRT647690	hsa-miR-5004-3p	HITS-CLIP	23824327
MIRT647689	hsa-miR-7856-5p	HITS-CLIP	23824327
MIRT647702	hsa-miR-6819-3p	HITS-CLIP	23824327
MIRT647700	hsa-miR-6877-3p	HITS-CLIP	23824327
MIRT647699	hsa-miR-6849-3p	HITS-CLIP	23824327
MIRT647698	hsa-miR-2682-3p	HITS-CLIP	23824327
MIRT647697	hsa-miR-6781-3p	HITS-CLIP	23824327
MIRT647696	hsa-miR-4320	HITS-CLIP	23824327
MIRT647695	hsa-miR-6512-3p	HITS-CLIP	23824327
MIRT647694	hsa-miR-6720-5p	HITS-CLIP	23824327
MIRT647693	hsa-miR-33a-5p	HITS-CLIP	23824327
MIRT647692	hsa-miR-33b-5p	HITS-CLIP	23824327
MIRT647691	hsa-miR-4503	HITS-CLIP	23824327
MIRT647690	hsa-miR-5004-3p	HITS-CLIP	23824327
MIRT647689	hsa-miR-7856-5p	HITS-CLIP	23824327
MIRT1172974	hsa-miR-338-3p	CLIP-seq
MIRT1172975	hsa-miR-3908	CLIP-seq
MIRT1172976	hsa-miR-4530	CLIP-seq
MIRT1172977	hsa-miR-4728-3p	CLIP-seq
MIRT1172978	hsa-miR-766	CLIP-seq
MIRT2050115	hsa-miR-1272	CLIP-seq
MIRT2050116	hsa-miR-3682-3p	CLIP-seq
MIRT2050117	hsa-miR-4731-5p	CLIP-seq
MIRT2050118	hsa-miR-615-5p	CLIP-seq
MIRT2577195	hsa-miR-1307	CLIP-seq
MIRT2577196	hsa-miR-1343	CLIP-seq
MIRT2577197	hsa-miR-1470	CLIP-seq
MIRT2577198	hsa-miR-3158-3p	CLIP-seq
MIRT2577199	hsa-miR-3195	CLIP-seq
MIRT1172974	hsa-miR-338-3p	CLIP-seq
MIRT2577200	hsa-miR-3615	CLIP-seq
MIRT2577201	hsa-miR-378g	CLIP-seq
MIRT1172975	hsa-miR-3908	CLIP-seq
MIRT2577202	hsa-miR-4280	CLIP-seq
MIRT2577203	hsa-miR-4437	CLIP-seq
MIRT2577204	hsa-miR-4446-3p	CLIP-seq
MIRT2577205	hsa-miR-4469	CLIP-seq
MIRT1172976	hsa-miR-4530	CLIP-seq
MIRT2577206	hsa-miR-4638-5p	CLIP-seq
MIRT2577207	hsa-miR-4667-3p	CLIP-seq
MIRT2577208	hsa-miR-4674	CLIP-seq
MIRT1172977	hsa-miR-4728-3p	CLIP-seq
MIRT2577209	hsa-miR-4787-3p	CLIP-seq
MIRT2577210	hsa-miR-4793-5p	CLIP-seq
MIRT2577211	hsa-miR-642a	CLIP-seq
MIRT1172978	hsa-miR-766	CLIP-seq
MIRT2050115	hsa-miR-1272	CLIP-seq
MIRT2577195	hsa-miR-1307	CLIP-seq
MIRT2577196	hsa-miR-1343	CLIP-seq
MIRT2577197	hsa-miR-1470	CLIP-seq
MIRT2577198	hsa-miR-3158-3p	CLIP-seq
MIRT2577199	hsa-miR-3195	CLIP-seq
MIRT1172974	hsa-miR-338-3p	CLIP-seq
MIRT2577200	hsa-miR-3615	CLIP-seq
MIRT2050116	hsa-miR-3682-3p	CLIP-seq
MIRT2577201	hsa-miR-378g	CLIP-seq
MIRT1172975	hsa-miR-3908	CLIP-seq
MIRT2577202	hsa-miR-4280	CLIP-seq
MIRT2577203	hsa-miR-4437	CLIP-seq
MIRT2577204	hsa-miR-4446-3p	CLIP-seq
MIRT2577205	hsa-miR-4469	CLIP-seq
MIRT2685737	hsa-miR-4502	CLIP-seq
MIRT1172976	hsa-miR-4530	CLIP-seq
MIRT2577206	hsa-miR-4638-5p	CLIP-seq
MIRT2577207	hsa-miR-4667-3p	CLIP-seq
MIRT2577208	hsa-miR-4674	CLIP-seq
MIRT1172977	hsa-miR-4728-3p	CLIP-seq
MIRT2577209	hsa-miR-4787-3p	CLIP-seq
MIRT2577210	hsa-miR-4793-5p	CLIP-seq
MIRT2577211	hsa-miR-642a	CLIP-seq
MIRT1172978	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003952	Function	NAD+ synthase (glutamine-hydrolyzing) activity	IBA
GO:0003952	Function	NAD+ synthase (glutamine-hydrolyzing) activity	IEA
GO:0003952	Function	NAD+ synthase (glutamine-hydrolyzing) activity	IMP	31883644
GO:0004359	Function	Glutaminase activity	IBA
GO:0004359	Function	Glutaminase activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956, 31515488, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0009435	Process	NAD+ biosynthetic process	IBA
GO:0009435	Process	NAD+ biosynthetic process	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0034354	Process	'de novo' NAD+ biosynthetic process from L-tryptophan	IEA
GO:0034354	Process	'de novo' NAD+ biosynthetic process from L-tryptophan	IMP	31883644
GO:0034355	Process	NAD+ biosynthetic process via the salvage pathway	IEA

Other IDs

• MIM: 608285
• HGNC: 29832
• e!Ensembl: ENSG00000172890

Protein

• UniProt ID: Q6IA69
• Protein name: Glutamine-dependent NAD(+) synthetase (EC 6.3.5.1) (NAD(+) synthase [glutamine-hydrolyzing]) (NAD(+) synthetase)
• Protein function: Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source.
• PDB: 6OFB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00795	CN_hydrolase	6 → 283	Carbon-nitrogen hydrolase	Family
  PF02540	NAD_synthase	337 → 651	NAD synthase	Domain

• Sequence:

  MGRKVTVATCALNQWALDFEGNLQRILKSIEIAKNRGARYRLGPELEICGYGCWDHYYES
  DTLLHSFQVLAALVESPVTQDIICDVGMPVMHRNVRYNCRVIFLNRKILLIRPKMALANE
  GNYRELRWFTPWSRSRHTEEYFLPRMIQDLTKQETVPFGDAVLVTWDTCIGSEICEELWT
  PHSPHIDMGLDGVEIITNASGSHQVLRKANTRVDLVTMVTSKNGGIYLLANQKGCDGDRL
  YYDGCAMIAMNGSVFAQGSQFSLDDVEVLTATLDLEDVRSYRAEISSRNLAASRASPYPR
  VKVDFALSCHEDLLAPISEPIEWKYHSPEEEISLGPACWLWDFLRRSQQAGFLLPLSGGV
  DSAATACLIYSMCCQVCEAVRSGNEEVLADVRTIVNQISYTPQDPRDLCGRILTTCYMAS
  KNSSQETCTRARELAQQIGSHHISLNIDPAVKAVMGIFSLVTGKSPLFAAHGGSSRENLA
  LQNVQARIRMVLAYLFAQLSLWSRGVHGGLLVLGSANVDESLLGYLTKYDCSSADINPIG
  GISKTDLRAFVQFCIQRFQLPALQSILLAPATAELEPLADGQVSQTDEEDMGMTYAELSV
  YGKLRKVAKMGPYSMFCKLLGMWRHICTPRQVADKVKRFFSKYSMNRHKMTTLTPAYHAE
  NYSPEDNRFDLRPFLYNTSWPWQFRCIENQVLQLERAEPQSLDGVD

• Sequence length: 706

Pathways

KEGG:

Nicotinate and nicotinamide metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Nicotinate metabolism

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
Congenital NAD deficiency disorder	Likely pathogenic; Pathogenic	rs144139747, rs1327307171, rs1949650831, rs1008561025, rs769220327	RCV001078184 RCV001078185 RCV001078189 RCV001078188 RCV001078186	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NADSYN1-related disorder	Likely pathogenic; Pathogenic	rs144139747	RCV003963002	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental delay	Likely pathogenic; Pathogenic	rs144139747	RCV002274118	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Vertebral, cardiac, renal, and limb defects syndrome 3	Likely pathogenic; Pathogenic	rs764123669, rs746448347, rs144139747, rs1327307171, rs1949650831, rs1008561025, rs769220327, rs368115694	RCV002273165 RCV003759816 RCV001035449 RCV001035450 RCV001035452 RCV001035454 RCV003758992 RCV001293858	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGENITAL VERTEBRAL, CARDIAC, RENAL ANOMALIES SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL VERTEBRAL-CARDIAC-RENAL ANOMALIES SYNDROME	—	Orphanet Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPEROPIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY BILIARY CIRRHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SMITH-LEMLI-OPITZ SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vertebral, cardiac, renal, and limb defects syndrome 1	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
VITAMIN DEFICIENCY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	23636220, 30796319, 35720397	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	8568107		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	22740028	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases Metabolic	Bone disease	Pubtator	30150596	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	36278823	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	23734184	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	24642724		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	22701574, 31104167	Associate	★☆☆☆☆ Found in Text Mining only
Congenital vertebral-cardiac-renal anomalies syndrome	Congenital Vertebral-Cardiac-Renal Anomalies Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	24642724		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	24642724		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	24642724		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	32764491, 37170809	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty liver	Pubtator	29761652	Associate	★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia Neonatal	Hyperbilirubinemia	Pubtator	37259065	Associate	★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	37834314	Associate	★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber congenital amaurosis	Pubtator	22842230	Associate	★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver cirrhosis	Pubtator	28415985	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	28062664	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	GWASCAT_DG	26502338		★☆☆☆☆ Found in Text Mining only
Multiple congenital anomalies	Multiple Congenital Anomalies	GENOMICS_ENGLAND_DG	31883644		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	34464857	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	30150596	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	27594614	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	23636220		★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	BEFREE	24073854		★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	Pubtator	24073854	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	31357732	Associate	★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin D Deficiency	GWASDB_DG	20541252		★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin D Deficiency	GWASCAT_DG	20541252		★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin d deficiency	Pubtator	22701574, 22785457, 26149120, 32231377, 34852423, 37259065, 37834314	Associate	★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin D Deficiency	BEFREE	22785457, 25370324, 26149120, 29153269		★☆☆☆☆ Found in Text Mining only