PGD
protein-codingphosphogluconate dehydrogenase
Gene summary
6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.9 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 PGD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002631.4. 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 | 2 | 1 | 2 | 5 | ||
| missense | 54 | 1 | 55 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 63 | 2 | 2 | 67 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002622.2 | 13 | MANE Select | |
| Ensembl | ENSP00000270776.8 | 13 | MANE Select | |
| RefSeq | NP_001291380.1 | 12 | Standard | |
| RefSeq | NP_001291381.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione metabolism - Homo sapiens (human)
- Pentose phosphate pathway - Homo sapiens (human)
- Pentose Phosphate Pathway (Erythrocyte)
- Warburg Effect
- Pentose Phosphate Pathway
Biological Process
- pentose-phosphate shunt
- pentose-phosphate shunt, oxidative branch
- pentose biosynthetic process
- D-gluconate metabolic process
- oxidation-reduction process
Molecular Function
- phosphogluconate dehydrogenase (decarboxylating) activity
- NADP binding
Cellular Component
- nucleus
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000270776
- Coding exons
- 13
- Length
- 21553
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 220 | 287 | 0.768 | 0.0000159 | 3166 |
| Missense (PolyPhen) | 71 | 128.65 | 0.55188 | 1416 | ||
| Synonymous | -0.920 | 129 | 116 | 1.11 | 0.00000703 | 930 |
| Loss of Function | 4.23 | 3 | 26.5 | 0.113 | 0.00000127 | 308 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the oxidative decarboxylation of 6- phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.838
Intolerance Scores
- LoFtool
- 0.408
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.76
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |