NAPRT
protein-codingnicotinate phosphoribosyltransferase
Gene summary
Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]
- NAPRT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NAPRT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145201.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 1 | 1 | 8 | ||
| missense | 107 | 6 | 113 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 121 | 7 | 1 | 129 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_660202.3 | 13 | MANE Select | |
| Ensembl | ENSP00000401508.2 | 13 | MANE Select | |
| RefSeq | NP_001273758.1 | 13 | Standard | |
| RefSeq | NP_001350074.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nicotinate and nicotinamide metabolism - Homo sapiens (human)
- NAD+ biosynthetic pathways
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- response to oxidative stress
- NAD biosynthetic process
- nicotinate nucleotide salvage
- NAD salvage
- NAD biosynthesis via nicotinamide riboside salvage pathway
Molecular Function
- nicotinate-nucleotide diphosphorylase (carboxylating) activity
- nicotinate phosphoribosyltransferase activity
- protein binding
- metal ion binding
Cellular Component
- extracellular region
- cytosol
- azurophil granule lumen
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000449291
- Coding exons
- 13
- Length
- 3865
- Individuals with no LoFs
- 125403
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 122
- Defined
- 125525
- p
- 0.000486
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.616 | 331 | 301 | 1.10 | 0.0000181 | 3330 |
| Missense (PolyPhen) | 129 | 116.36 | 1.1086 | 1278 | ||
| Synonymous | -1.21 | 157 | 139 | 1.13 | 0.00000855 | 1204 |
| Loss of Function | -0.164 | 27 | 26.1 | 1.03 | 0.00000150 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00073 | 0.00068 | rare |
| Latino/Admixed American | 0.00045 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00050 | 0.00049 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00056 | 0.00053 | rare |
| South Asian | 0.00077 | 0.00075 | rare |
| Other | 0.00069 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D- ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate (PubMed:17604275, PubMed:21742010, PubMed:26042198). Helps prevent cellular oxidative stress via its role in NAD biosynthesis (PubMed:17604275). {ECO:0000269|PubMed:17604275, ECO:0000269|PubMed:21742010, ECO:0000269|PubMed:26042198}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- RVIS EVS
- -1.02
- RVIS percentile EVS
- 8.1
Essentials
- Essential (gene trap)
- N