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ACADSB
acyl-CoA dehydrogenase short/branched chain
The ACADSB gene provides instructions for an enzyme essential in breaking down amino acids, particularly isoleucine, within cellular mitochondria. The ACADSB gene encodes the enzyme short/branched chain acyl-CoA dehydrogenase (SBCAD), which is critical for processing certain amino acids from dietary proteins.
ACADSB is located on the long (q) arm of chromosome 10, at band 10q26.13. Arm ratio per GRCh38 - banding schematic.
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Overview
The ACADSB gene, also known by aliases such as 2-MEBCAD and SBCAD, plays a crucial role in human metabolism. It provides the genetic blueprint for an enzyme responsible for breaking down certain amino acids derived from proteins consumed in the diet. This metabolic process is vital for converting food into usable energy within the body's cells.
The enzyme produced from the ACADSB gene is specifically active within the mitochondria, often referred to as the 'powerhouses' of the cell, where energy production occurs. Proper functioning of this enzyme is therefore fundamental for maintaining normal cellular energy balance.
What the gene does
The ACADSB gene directs the synthesis of an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD). This enzyme is primarily involved in the catabolism, or breakdown, of amino acids, particularly isoleucine. When proteins are digested, they are broken down into individual amino acids, which can then be further processed to generate energy.
Within the mitochondria, SBCAD performs a key step in this metabolic pathway. Specifically, it catalyses the conversion of 2-methylbutyryl-CoA to tiglyl-CoA. This reaction is the third step in the broader pathway that ultimately transforms isoleucine into molecules the body can use for energy. The SBCAD enzyme also contributes to the breakdown of other amino acids through similar chemical reactions, highlighting its broad importance in amino acid metabolism.
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Chromosome location
The ACADSB gene is situated on chromosome 10, specifically at position 10q26.13. This indicates its location on the long arm (q) of chromosome 10, within region 26, band 13. The gene's precise location on the human genome helps researchers understand its genomic context and potential interactions with other genes.
Protein structure
The ACADSB gene encodes a protein that is 432 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations, or variants, in the ACADSB gene can alter the enzyme's structure or function, potentially impacting its ability to process amino acids effectively. These changes can range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. Research has identified various ACADSB gene mutations in individuals with specific 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.1159G>A | p.Glu387Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.1165A>G | p.Met389Val | Pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.1228G>A | p.Gly410Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.275C>G | p.Ser92Ter | Pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.295C>T | p.Gln99Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.303+3A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | ACADSB-related disorder |
c.375dup | p.Glu126fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.478del | p.Ala160fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.621G>A | p.Trp207Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
c.653dup | p.Val219fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of 2-methylbutyryl-CoA dehydrogenase |
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
Variations in the ACADSB gene are primarily associated with a condition known as short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency. While many individuals with identified ACADSB gene mutations may not experience any health problems, some can present with a range of symptoms. These may include reduced energy (lethargy), muscle weakness, seizures, and developmental delays, indicating the enzyme's importance for neurological and muscular function.
No disease links recorded for this gene in our reference set.
UK clinical status
The ACADSB gene is listed on NHS England's National Genomic Test Directory. It is categorised as relevant for investigating 'Likely inborn error of metabolism' and 'Undiagnosed metabolic disorders', as indicated by its 'green' status on PanelApp, signifying it is of high clinical utility for these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ACADSB gene?
The ACADSB gene provides instructions for making an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD). This enzyme is crucial for breaking down certain amino acids, particularly isoleucine, within the mitochondria to help generate cellular energy.
Where in the body does the ACADSB enzyme primarily function?
The ACADSB enzyme is found within the mitochondria of cells throughout the body. Mitochondria are specialised cellular structures responsible for converting energy from food into a form that cells can utilise.
What health conditions are associated with ACADSB gene variations?
Variations in the ACADSB gene are primarily linked to short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency. While many individuals with these variations may be asymptomatic, some can experience symptoms such as lethargy, muscle weakness, seizures, and developmental delays.
References
- Alfardan J, Mohsen AW, Copeland S. Characterization of new ACADSB gene sequence mutations and clinical implications in patients with 2-methylbutyrylglycinuria identified by newborn screening. Molecular genetics and metabolism. 2010. PMID: 20547083
- Sass JO, Ensenauer R, Röschinger W. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency: functional and molecular studies on a defect in isoleucine catabolism. Molecular genetics and metabolism. 2008. PMID: 17945527
- Pasquali M, Monsen G, Richardson L. Biochemical findings in common inborn errors of metabolism. American journal of medical genetics. Part C, Seminars in medical genetics. 2006. PMID: 16602099
- Korman SH. Inborn errors of isoleucine degradation: a review. Molecular genetics and metabolism. 2006. PMID: 16950638
- Andresen BS, Christensen E, Corydon TJ. Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. American journal of human genetics. 2000. PMID: 11013134