NMNAT2

nicotinamide nucleotide adenylyltransferase 2

Basic information

Region (hg38): 1:183248236-183418380

Previous symbols: [ "C1orf15" ]

Links

ENSG00000157064 ∙ NCBI:23057 ∙ OMIM:608701 ∙ HGNC:16789 ∙ Uniprot:Q9BZQ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NMNAT2 gene.

• Inborn genetic diseases (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NMNAT2 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						0
missense		1	8			9
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	8	0	0

Variants in NMNAT2

This is a list of pathogenic ClinVar variants found in the NMNAT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-183261260-C-T		not specified	Likely pathogenic (Jul 29, 2021)
1-183284001-C-G		not specified	Uncertain significance (Sep 14, 2022)
1-183284730-A-G		not specified	Uncertain significance (Feb 07, 2023)
1-183284754-C-T		not specified	Uncertain significance (Dec 06, 2023)
1-183284755-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-183286683-C-T		Vascular dementia	Uncertain significance (Oct 01, 2021)
1-183286701-T-C		not specified	Uncertain significance (Jun 05, 2023)
1-183286706-T-TG		Inborn genetic diseases	Likely pathogenic (Jul 01, 2015)
1-183286731-C-T		not specified	Uncertain significance (Sep 17, 2021)
1-183290157-C-T		not specified	Uncertain significance (Jul 06, 2022)
1-183292798-A-T		not specified	Uncertain significance (Sep 17, 2021)
1-183292841-C-T		not specified	Uncertain significance (May 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NMNAT2	protein_coding	protein_coding	ENST00000287713	11	170366

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0115	125741	0	2	125743	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	110	192	0.573	0.0000114	2022
Missense in Polyphen		40	76.742	0.52123		761
Synonymous	0.0524	75	75.6	0.992	0.00000481	589
Loss of Function	3.70	1	17.9	0.0559	8.44e-7	201

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor (By similarity). Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:16118205, PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency (PubMed:16118205, PubMed:17402747). Cannot use triazofurin monophosphate (TrMP) as substrate (PubMed:16118205, PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:16118205, PubMed:17402747). For the pyrophosphorolytic activity prefers NAD(+), NADH and NaAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively (PubMed:16118205, PubMed:17402747). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:16118205, PubMed:17402747). Axon survival factor required for the maintenance of healthy axons: acts by delaying Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons (By similarity). {ECO:0000250|UniProtKB:Q8BNJ3, ECO:0000269|PubMed:16118205, ECO:0000269|PubMed:17402747}.
• Pathway: Nicotinate and nicotinamide metabolism - Homo sapiens (human);Nicotinate and Nicotinamide Metabolism;NAD+ metabolism;Metabolism;Nicotinate Nicotinamide metabolism;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;NAD salvage;NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde;NAD <i>de novo</i> biosynthesis;superpathway of tryptophan utilization (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.0269
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.612
• hipred: Y
• hipred_score: 0.752
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nmnat2
• Phenotype: growth/size/body region phenotype; muscle phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype

Gene ontology

• Biological process: NAD biosynthetic process;NAD metabolic process;'de novo' NAD biosynthetic process from aspartate
• Cellular component: Golgi membrane;late endosome;Golgi apparatus;trans-Golgi network;axon;cytoplasmic vesicle membrane;synapse
• Molecular function: nicotinamide-nucleotide adenylyltransferase activity;nicotinate-nucleotide adenylyltransferase activity;ATP binding