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PDHB
pyruvate dehydrogenase E1 subunit beta
The PDHB gene provides instructions for a protein critical to the pyruvate dehydrogenase complex, which plays a vital role in converting food energy into a usable form for cells. The PDHB gene is essential for cellular energy production, encoding a subunit of the pyruvate dehydrogenase complex.
PDHB is located on the short (p) arm of chromosome 3, at band 3p14.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The PDHB gene encodes the E1 beta subunit of the pyruvate dehydrogenase complex, a crucial enzyme system within cellular metabolism. This complex facilitates the conversion of pyruvate, derived from carbohydrates, into acetyl-CoA, which is a key step in generating cellular energy [PMID:30000843]. Understanding the PDHB gene's role is important for comprehending conditions linked to impaired energy production.
The protein produced by the PDHB gene is integral to the overall function of the pyruvate dehydrogenase complex. Proper function of this complex is necessary for brain development and overall physiological health, as it supplies energy for various bodily processes.
What the gene does
The PDHB gene directs the synthesis of the E1 beta protein, which forms part of the pyruvate dehydrogenase E1 enzyme. This E1 enzyme combines two E1 beta proteins with two E1 alpha proteins (derived from the PDHA1 gene) [PMID:30000843]. Together, these components constitute the E1 enzyme, an essential part of the larger pyruvate dehydrogenase complex.
The pyruvate dehydrogenase complex is fundamental to the body's energy pathways, converting chemical energy from food into a form cells can use, primarily adenosine triphosphate (ATP) [PMID:30000843]. Specifically, the E1 enzyme within this complex initiates the conversion of pyruvate, a molecule resulting from carbohydrate breakdown, into acetyl-CoA. This conversion is a gateway step that allows carbohydrates to enter the Krebs cycle, a central pathway for energy generation in the cell.
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Chromosome location
The PDHB gene is located on chromosome 3, specifically at band 3p14.3. This genomic position helps define its location within the human genome. The gene spans a particular region of this chromosome, contributing to the broader understanding of gene mapping and organisation.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants within the PDHB gene can alter the structure or function of the E1 beta protein. These changes may impact the efficiency of the pyruvate dehydrogenase complex, affecting the body's ability to produce energy. Different types of genetic changes, including single nucleotide alterations, may be observed.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.122_123del | p.Gln41fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.211C>T | p.Arg71Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.238_239del | p.Lys80fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.301A>G | p.Met101Val | Pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.692_695del | p.Glu231fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.716_717del | p.Val239fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.461dup | p.Ala155fs | Pathogenic | ★☆☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.533_534delinsAA | p.Trp178Ter | Pathogenic | ★☆☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.578del | p.Asp193fs | Pathogenic | ★☆☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
c.650dup | p.Ser218fs | Pathogenic | ★☆☆☆ | Pyruvate dehydrogenase E1-beta deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the PDHB gene are associated with pyruvate dehydrogenase deficiency, a rare metabolic condition. This disorder can lead to a build-up of lactic acid in the body, known as lactic acidosis, and may also be associated with developmental delays and neurological issues. The condition arises from impaired function of the pyruvate dehydrogenase complex, impacting cellular energy production.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PDHB variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The PDHB gene is included in several NHS England Genomic Medicine Service national panels, indicating its clinical relevance in the UK. It is assessed for conditions such as Foetal anomalies, Intellectual disability, Mitochondrial disorders, and Pyruvate dehydrogenase (PDH) deficiency. Its inclusion suggests its role in diagnosing and understanding these complex conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the PDHB gene?
The PDHB gene provides instructions for making the E1 beta subunit of the pyruvate dehydrogenase E1 enzyme. This enzyme is crucial for the pyruvate dehydrogenase complex, which converts carbohydrates into energy for cells.
What condition is associated with variants in the PDHB gene?
Variants in the PDHB gene are associated with pyruvate dehydrogenase deficiency. This is a rare metabolic disorder characterised by lactic acidosis, developmental delays, and neurological problems due to impaired energy production.
How is pyruvate dehydrogenase deficiency inherited?
Pyruvate dehydrogenase deficiency caused by PDHB gene variants typically follows an autosomal recessive inheritance pattern. This means an individual must inherit two altered copies of the gene (one from each parent) to develop the condition.
References
- Patel MS, Korotchkina LG, Sidhu S. Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex. Journal of molecular catalysis. B, Enzymatic. 2009. PMID: 20160912
- Okajima K, Korotchkina LG, Prasad C. Mutations of the E1beta subunit gene (PDHB) in four families with pyruvate dehydrogenase deficiency. Molecular genetics and metabolism. 2008. PMID: 18164639
- Brown RM, Head RA, Boubriak II. Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. Human genetics. 2004. PMID: 15138885
- Adam MP, Bick S, Mirzaa GM. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 1993. PMID: 34138529