NADSYN1

NAD synthetase 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 11:71453108-71524107

Links

ENSG00000172890 ∙ NCBI:55191 ∙ OMIM:608285 ∙ HGNC:29832 ∙ Uniprot:Q6IA69 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vertebral, cardiac, renal, and limb defects syndrome 3 (Moderate), mode of inheritance: AR
• congenital vertebral-cardiac-renal anomalies syndrome (Supportive), mode of inheritance: AR
• vertebral, cardiac, renal, and limb defects syndrome 3 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vertebral, cardiac, renal, and limb defects syndrome 3	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Pulmonary; Renal	31883644

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NADSYN1 gene.

• Inborn genetic diseases (35 variants)
• not provided (20 variants)
• Vertebral, cardiac, renal, and limb defects syndrome 3 (17 variants)
• NADSYN1-related condition (2 variants)
• Congenital NAD deficiency disorder (2 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NADSYN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	6	7
missense		2	42	2	3	49
nonsense		1	1			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region			1		1	2
non coding					5	5
Total	1	3	45	3	14

Highest pathogenic variant AF is 0.0000263

Variants in NADSYN1

This is a list of pathogenic ClinVar variants found in the NADSYN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-71453378-A-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
11-71455108-A-C			Pathogenic (Jan 01, 2022)
11-71455169-T-C		Congenital NAD deficiency disorder • Vertebral, cardiac, renal, and limb defects syndrome 3	Pathogenic (May 10, 2023)
11-71458478-C-T		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
11-71458501-G-C		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71458534-G-A			Uncertain significance (Oct 25, 2019)
11-71458535-A-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
11-71463406-A-G		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71463437-TA-T		Vertebral, cardiac, renal, and limb defects syndrome 3	Conflicting classifications of pathogenicity (May 10, 2023)
11-71463507-C-T		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71464078-A-G		Inborn genetic diseases	Uncertain significance (Jul 21, 2021)
11-71464081-G-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
11-71464105-C-T		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
11-71464114-C-T		Inborn genetic diseases • Vertebral, cardiac, renal, and limb defects syndrome 3	Conflicting classifications of pathogenicity (May 10, 2023)
11-71464119-G-T		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
11-71464128-G-A			Likely benign (Feb 01, 2024)
11-71464130-G-T		Congenital NAD deficiency disorder • NADSYN1-related disorder	Uncertain significance (Mar 06, 2023)
11-71472428-C-T		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71472431-C-T		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71473326-A-C		Inborn genetic diseases	Uncertain significance (Apr 08, 2022)
11-71473342-G-A		Vertebral, cardiac, renal, and limb defects syndrome 3	Pathogenic/Likely pathogenic (May 10, 2023)
11-71473571-C-T		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
11-71473582-A-G		Inborn genetic diseases	Uncertain significance (Nov 23, 2022)
11-71473632-A-C		Vertebral, cardiac, renal, and limb defects syndrome 3	Benign (Sep 05, 2021)
11-71473640-G-A		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NADSYN1	protein_coding	protein_coding	ENST00000319023	21	70999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.25e-16	0.682	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.710	407	449	0.906	0.0000282	4612
Missense in Polyphen		156	171.98	0.90708		1773
Synonymous	-1.01	210	192	1.09	0.0000145	1351
Loss of Function	1.89	32	45.8	0.699	0.00000243	476

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000669	0.000659
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000426	0.000416
European (Non-Finnish)	0.000409	0.000404
Middle Eastern	0.000381	0.000381
South Asian	0.000755	0.000752
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Nicotinate and nicotinamide metabolism - Homo sapiens (human);2-Hydroxyglutric Aciduria (D And L Form);Nicotinate and Nicotinamide Metabolism;Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;NAD Biosynthesis II (from tryptophan);NAD+ biosynthetic pathways;Metabolism;Nicotinate Nicotinamide metabolism;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde;NAD <i>de novo</i> biosynthesis;superpathway of tryptophan utilization (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.258
• rvis_EVS: -0.21
• rvis_percentile_EVS: 37.78

Haploinsufficiency Scores

• pHI: 0.0902
• hipred: N
• hipred_score: 0.443
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nadsyn1
• Phenotype: reproductive system phenotype

Gene ontology

• Biological process: NAD biosynthetic process;NAD metabolic process
• Cellular component: cytoplasm;cytosol
• Molecular function: NAD+ synthase (glutamine-hydrolyzing) activity;glutaminase activity;protein binding;ATP binding