QPRT
protein-codingquinolinate phosphoribosyltransferase
Gene summary
This gene encodes a key enzyme in catabolism of quinolinate, an intermediate in the tryptophan-nicotinamide adenine dinucleotide pathway. Quinolinate acts as a most potent endogenous exitotoxin to neurons. Elevation of quinolinate levels in the brain has been linked to the pathogenesis of neurodegenerative disorders such as epilepsy, Alzheimer's disease, and Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.4 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 QPRT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014298.6. 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 | 1 | 2 | 3 | |||
| missense | 41 | 1 | 42 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 47 | 3 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055113.3 | 4 | MANE Select | |
| Ensembl | ENSP00000378782.4 | 4 | MANE Select | |
| RefSeq | NP_001305178.1 | 3 | Standard | |
| RefSeq | NP_001305179.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nicotinate and nicotinamide metabolism - Homo sapiens (human)
- Nicotinate and Nicotinamide Metabolism
- NAD Biosynthesis II (from tryptophan)
- NAD+ biosynthetic pathways
- Metabolism
Biological Process
- NAD biosynthetic process
- NAD metabolic process
- quinolinate catabolic process
- protein complex oligomerization
Molecular Function
- nicotinate-nucleotide diphosphorylase (carboxylating) activity
- protein binding
- protein homodimerization activity
Cellular Component
- cytoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395384
- Coding exons
- 4
- Length
- 35421
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125705
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 148 | 192 | 0.772 | 0.0000123 | 1868 |
| Missense (PolyPhen) | 67 | 87.384 | 0.76673 | 893 | ||
| Synonymous | 0.0669 | 96 | 96.8 | 0.991 | 0.00000727 | 681 |
| Loss of Function | 1.37 | 5 | 9.58 | 0.522 | 4.95e-7 | 97 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00021 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.00079 | 0.00078 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the catabolism of quinolinic acid (QA). {ECO:0000269|PubMed:17868694}.;
Recessive Scores
- pRec
- 0.179
Intolerance Scores
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |