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ACADSB
acyl-CoA dehydrogenase short/branched chain
The ACADSB gene provides instructions for an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD), which is crucial for processing certain amino acids to generate energy. The ACADSB gene encodes the SBCAD enzyme, locating it within mitochondria where it helps break down amino acids like isoleucine.
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 is responsible for producing the short/branched chain acyl-CoA dehydrogenase (SBCAD) enzyme. This enzyme plays a fundamental role in metabolic processes within the body, specifically in the breakdown of proteins. It converts amino acids obtained from food into forms that can be used by cells for energy.
SBCAD is primarily found in the mitochondria, which are often referred to as the 'powerhouses' of the cell. Proper functioning of the ACADSB gene and its enzyme product is essential for efficient energy conversion and overall cellular metabolism.
What the gene does
The ACADSB gene provides instructions for synthesising the short/branched chain acyl-CoA dehydrogenase (SBCAD) enzyme, also known as 2-methylbutyryl-CoA dehydrogenase. This enzyme is primarily active within the mitochondria of various cells throughout the body. Its main function is to facilitate the breakdown of specific amino acids, which are the building blocks of proteins.
SBCAD is particularly important in the metabolism of isoleucine. It catalyses a key step in this pathway, converting 2-methylbutyryl-CoA into tiglyl-CoA. This conversion is part of a larger series of reactions that ultimately transform amino acids into molecules the body can use for energy. The enzyme also assists in similar chemical reactions for the breakdown of other amino acids, highlighting its broad importance in energy metabolism.
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Chromosome location
The ACADSB gene is located on chromosome 10. Its precise position is at band 10q26.13, which refers to a specific region on the long arm (q) of chromosome 10. The gene is situated towards the end of this chromosome.
Protein structure
The ACADSB gene codes for 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 within the ACADSB gene can alter the function or production of the SBCAD enzyme. These variations range from single nucleotide changes to larger deletions or insertions within the gene sequence. Such changes can impact the enzyme's efficiency in breaking down amino acids, leading to potential metabolic disruptions.
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 | ★★☆☆ | ACADSB-related disorder |
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 | ★★☆☆ | ACADSB-related disorder |
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 associated with short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency. This condition arises when the SBCAD enzyme does not function correctly, impairing the body's ability to process certain amino acids. While many individuals with SBCAD deficiency may experience no health complications, some can present with symptoms such as reduced energy, muscle weakness, seizures, or developmental delays.
No disease links recorded for this gene in our reference set.
UK clinical status
The ACADSB gene is recognised within the UK's NHS Genomic Medicine Service pathways. It is listed on PanelApp under panels related to 'Likely inborn error of metabolism' and 'Undiagnosed metabolic disorders', both with a green status, indicating strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the ACADSB gene do?
The ACADSB gene provides instructions for creating an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD). This enzyme is crucial for breaking down certain amino acids, like isoleucine, into molecules that the body can use for energy.
What is short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency?
SBCAD deficiency is a condition caused by variations in the ACADSB gene. It means the body has difficulty processing particular amino acids, potentially leading to symptoms such as lethargy, muscle weakness, or developmental delays in some affected individuals.
Where in the cell does the SBCAD enzyme function?
The SBCAD enzyme primarily functions within the mitochondria of cells. Mitochondria are the organelles responsible for converting nutrients from food into usable energy for the cell, making the SBCAD enzyme's role in this process vital.
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