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ETFB
electron transfer flavoprotein subunit beta
The ETFB gene provides instructions for making a vital component of the electron transfer flavoprotein enzyme, which is essential for cellular energy production by breaking down fats and proteins. The ETFB gene encodes the beta subunit of electron transfer flavoprotein (ETF), an enzyme predominantly found in the mitochondria.
ETFB is located on the long (q) arm of chromosome 19, at band 19q13.41. Arm ratio per GRCh38 - banding schematic.
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Overview
The ETFB gene, or electron transfer flavoprotein subunit beta, is fundamental for cellular energy metabolism. It contains the genetic blueprint for the beta subunit of the electron transfer flavoprotein enzyme. This enzyme is primarily located in the mitochondria, where it plays a critical role in converting fats and proteins into usable energy.
What the gene does
The electron transfer flavoprotein (ETF) enzyme, which includes the ETFB subunit, is crucial for metabolic processes within mitochondria. Within mitochondria, this enzyme participates in the cascade of biochemical reactions that extract energy from dietary fats and proteins [PMID:11894085]. A properly functioning ETFB subunit is essential for the overall activity of the ETF enzyme, ensuring these metabolic pathways operate effectively. Disruption of the ETFB subunit compromises the enzyme's ability to support efficient energy metabolism [PMID:11894085].
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Chromosome location
The ETFB gene is situated on chromosome 19, specifically at locus 19q13.41. This genomic location refers to the long (q) arm of chromosome 19, within band 13.41. The gene's precise position helps in understanding its genetic context and how it might be inherited.
Protein structure
The ETFB gene codes for a protein consisting of 255 amino acids. This protein forms the beta subunit of the electron transfer flavoprotein. Within its structure, a segment known as the Recognition loop is identified, spanning amino acid positions 183-205.
Key variants
Genetic variations within the ETFB gene can affect the function of the electron transfer flavoprotein beta subunit. These variations range from single nucleotide changes to larger alterations that may impact protein production or function. Understanding these variants is crucial for assessing their potential role in metabolic conditions.
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.124T>C | p.Cys42Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.178G>T | p.Glu60Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.253C>T | p.Arg85Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.406C>T | p.Gln136Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.491G>A | p.Arg164Gln | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.61C>T | p.Arg21Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.61del | p.Arg21fs | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
Single allele | - | Pathogenic | ★★☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.368del | p.Gly123fs | Pathogenic | ★☆☆☆ | Multiple acyl-CoA dehydrogenase deficiency |
c.81del | p.Gly28fs | Pathogenic | ★☆☆☆ | Multiple acyl-CoA dehydrogenase 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
Pathogenic variants in the ETFB gene are associated with inherited metabolic disorders, most notably Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as Glutaric acidaemia type II (GA-II). This condition follows an autosomal recessive inheritance pattern, meaning an individual must inherit two affected copies of the gene to develop the disorder. Certain genetic changes in ETFB can block the production of the electron transfer flavoprotein enzyme entirely, while alternative variants may lead to an enzyme product that lacks normal function.
- Multiple acyl-CoA dehydrogenase deficiency (MADD / GA-II) Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic ETFB 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 ETFB gene is included in several UK NHS national genomic testing panels, indicating its clinical significance within the UK healthcare system. These panels cover conditions such as Acute rhabdomyolysis, Foetal anomalies, Hyperammonaemia, Intellectual disability, Rhabdomyolysis and metabolic muscle disorders, and Undiagnosed metabolic disorders. It is also part of the DDG2P and Likely inborn error of metabolism panels, highlighting its role in diagnosing a range of severe and early-onset genetic conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ETFB gene?
The ETFB gene provides instructions for making the beta subunit of the electron transfer flavoprotein enzyme. This enzyme is crucial for breaking down fats and proteins in the mitochondria to produce cellular energy.
What condition is associated with variants in the ETFB gene?
Variants in the ETFB gene are associated with Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as Glutaric acidaemia type II (GA-II), which is an inherited metabolic disorder affecting the body's ability to process fats and proteins.
How is Multiple acyl-CoA dehydrogenase deficiency (MADD) inherited?
Multiple acyl-CoA dehydrogenase deficiency (MADD) is inherited in an autosomal recessive pattern. This means an individual must inherit two pathogenic copies of the ETFB gene, one from each parent, to develop the condition.
References
- Schiff M, Froissart R, Olsen RK. Electron transfer flavoprotein deficiency: functional and molecular aspects. Molecular genetics and metabolism. 2006. PMID: 16510302
- Olsen RK, Andresen BS, Christensen E. DNA-based prenatal diagnosis for severe and variant forms of multiple acyl-CoA dehydrogenation deficiency. Prenatal diagnosis. 2005. PMID: 15662686
- Curcoy A, Olsen RK, Ribes A. Late-onset form of beta-electron transfer flavoprotein deficiency. Molecular genetics and metabolism. 2003. PMID: 12706375
- Olsen RK, Andresen BS, Christensen E. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Human mutation. 2003. PMID: 12815589
- White RA, Dowler LL, Angeloni SV. Assignment of Etfdh, Etfb, and Etfa to chromosomes 3, 7, and 13: the mouse homologs of genes responsible for glutaric acidemia type II in human. Genomics. 1996. PMID: 8617498
- Whitfield J, Hurst D, Bennett MJ. Fetal polycystic kidney disease associated with glutaric aciduria type II: an inborn error of energy metabolism. American journal of perinatology. 1996. PMID: 8688100