NADSYN1

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

Basic information

Region (hg38): 11:71453109-71524107

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
• vertebral, cardiac, renal, and limb defects syndrome 3 (Strong), 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 (85 variants)
• not_provided (22 variants)
• Vertebral,_cardiac,_renal,_and_limb_defects_syndrome_3 (22 variants)
• NADSYN1-related_disorder (15 variants)
• Congenital_NAD_deficiency_disorder (6 variants)
• Neurodevelopmental_delay (1 variants)
• Vertebral,_cardiac,_renal,_and_limb_defects_syndrome_1 (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. These statistics are base on transcript: NM_000018161.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	4	8
missense	1	5	94	4	1	105
nonsense	2	3	1			6
start loss						0
frameshift	1	1				2
splice donor/acceptor (+/-2bp)	2		2			4
Total	6	9	97	8	5

Highest pathogenic variant AF is 0.00117537

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