PDHA2
protein-codingpyruvate dehydrogenase E1 subunit alpha 2
Gene summary
Enables pyruvate dehydrogenase (acetyl-transferring) activity. Involved in pyruvate decarboxylation to acetyl-CoA. Located in mitochondrion. Part of pyruvate dehydrogenase complex. Implicated in spermatogenic failure 70. [provided by Alliance of Genome Resources, Jun 2026]
- PDHAL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030733
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0030733
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PDHA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005390.5. 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 | 1 | 1 | ||||
| missense | 1 | 59 | 2 | 62 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 59 | 0 | 3 | 63 |
Highest pathogenic variant AF is 0.00007124652
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005381.1 | 1 | MANE Select | |
| Ensembl | ENSP00000295266.4 | 1 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Citrate cycle (TCA cycle) - Homo sapiens (human)
- Pyruvate metabolism - Homo sapiens (human)
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Central carbon metabolism in cancer - Homo sapiens (human)
- HIF-1 signaling pathway - Homo sapiens (human)
Biological Process
- glucose metabolic process
- acetyl-CoA biosynthetic process from pyruvate
- pyruvate metabolic process
- tricarboxylic acid cycle
Molecular Function
- pyruvate dehydrogenase (acetyl-transferring) activity
- pyruvate dehydrogenase (NAD+) activity
Cellular Component
- nucleus
- nucleolus
- mitochondrion
- mitochondrial matrix
- pyruvate dehydrogenase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295266
- Coding exons
- 1
- Length
- 1387
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.260 | 242 | 231 | 1.05 | 0.0000141 | 2518 |
| Missense (PolyPhen) | 105 | 96.764 | 1.0851 | 1071 | ||
| Synonymous | -0.435 | 94 | 88.8 | 1.06 | 0.00000573 | 786 |
| Loss of Function | -0.455 | 12 | 10.4 | 1.15 | 7.11e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:16436377}.;
Recessive Scores
- pRec
- 0.275
Intolerance Scores
- LoFtool
- 0.270
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |