PDP2
protein-codingpyruvate dehydrogenase phosphatase catalytic subunit 2, the group of Protein phosphatases, Mg2+/Mn2+ dependent
Gene summary
This gene is a mitochondrial protein that functions as a phosphatase and is involved in the enzymatic resetting of the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.2 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 PDP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020786.4. 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 | 0 | |||||
| missense | 72 | 7 | 79 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 73 | 7 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065837.1 | 1 | MANE Select | |
| Ensembl | ENSP00000309548.2 | 1 | MANE Select | |
| RefSeq | NP_001316857.1 | 1 | Standard | |
| RefSeq | NP_001316858.1 | 1 | 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
- positive regulation of pyruvate dehydrogenase activity
Molecular Function
- protein serine/threonine phosphatase activity
- magnesium-dependent protein serine/threonine phosphatase activity
- [pyruvate dehydrogenase (lipoamide)] phosphatase activity
- metal ion binding
Cellular Component
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000311765
- Coding exons
- 1
- Length
- 17166
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125748
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.30 | 236 | 299 | 0.789 | 0.0000163 | 3456 |
| Missense (PolyPhen) | 59 | 94.626 | 0.62351 | 1115 | ||
| Synonymous | -0.575 | 137 | 129 | 1.06 | 0.00000721 | 1085 |
| Loss of Function | 1.67 | 9 | 16.3 | 0.554 | 9.35e-7 | 177 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.743
- RVIS EVS
- -0.93
- RVIS percentile EVS
- 9.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.913
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |