NMNAT2
nicotinamide nucleotide adenylyltransferase 2
Basic information
Region (hg38): 1:183248237-183418380
Previous symbols: [ "C1orf15" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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 | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 2 | 9 | 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) | ||
| 1-183261291-C-A | not specified | Uncertain significance (Sep 03, 2024) | ||
| 1-183284001-C-G | not specified | Uncertain significance (Sep 14, 2022) | ||
| 1-183284713-C-A | not specified | Uncertain significance (Mar 30, 2024) | ||
| 1-183284730-A-G | not specified | Uncertain significance (Feb 07, 2023) | ||
| 1-183284736-G-A | not specified | Uncertain significance (Jun 26, 2024) | ||
| 1-183284739-C-T | not specified | Uncertain significance (Oct 11, 2024) | ||
| 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:
| 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:
- 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