PDPR
protein-codingpyruvate dehydrogenase phosphatase regulatory subunit
Gene summary
Pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate and links glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. The dephosphorylation and reactivation of PDC is catalyzed by pyruvate dehydrogenase phosphatase (PDP). The dimeric PDP has a catalytic subunit and a regulatory subunit. This gene encodes the FAD-containing regulatory subunit of PDP. The encoded protein acts to decrease the sensitivity of the PDP catalytic subunit to magnesium ions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.2 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 PDPR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017990.5. 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 | 3 | 3 | ||||
| missense | 143 | 5 | 148 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 143 | 8 | 0 | 151 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060460.4 | 17 | MANE Select | |
| Ensembl | ENSP00000288050.5 | 17 | MANE Select | |
| RefSeq | NP_001309046.1 | 17 | Standard | |
| RefSeq | NP_001309047.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of pyruvate dehydrogenase (PDH) complex
- Pyruvate metabolism
- Pyruvate metabolism and Citric Acid (TCA) cycle
- The citric acid (TCA) cycle and respiratory electron transport
- Metabolism
Biological Process
- protein dephosphorylation
- regulation of acetyl-CoA biosynthetic process from pyruvate
- oxidation-reduction process
Molecular Function
- [pyruvate dehydrogenase (lipoamide)] phosphatase activity
- oxidoreductase activity
Cellular Component
- cytoplasm
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000288050
- Coding exons
- 17
- Length
- 47675
- Individuals with no LoFs
- 124396
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 265
- Defined
- 124661
- p
- 0.00106
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.494 | 499 | 469 | 1.06 | 0.0000263 | 5547 |
| Missense (PolyPhen) | 176 | 172.45 | 1.0206 | 1968 | ||
| Synonymous | -1.14 | 196 | 177 | 1.11 | 0.0000105 | 1599 |
| Loss of Function | 3.29 | 21 | 44.7 | 0.470 | 0.00000243 | 498 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0020 | 0.0020 | notable |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0.0064 | 0.0064 | notable |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00079 | 0.00078 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0.0012 | 0.0012 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Decreases the sensitivity of PDP1 to magnesium ions, and this inhibition is reversed by the polyamine spermine. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.450
- RVIS EVS
- 0.87
- RVIS percentile EVS
- 88.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.174
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |