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ACADS

acyl-CoA dehydrogenase short chain

The ACADS gene provides instructions for making the short-chain acyl-CoA dehydrogenase (SCAD) enzyme, which is crucial for breaking down certain fats into energy. The ACADS gene is responsible for producing the SCAD enzyme, an important component of cellular energy production.

Chromosome 12q24.31 Autosomal recessive HGNC:90 Tier C
ACADS 12q24.31 p arm q arm 12

ACADS is located on the long (q) arm of chromosome 12, at band 12q24.31. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 12 in the library →

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Clinical tests that include this

Carrier Screening panel
ACADS is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ACADS gene encodes an enzyme called short-chain acyl-CoA dehydrogenase (SCAD). This enzyme plays a vital role in cellular metabolism, specifically in the process of fatty acid oxidation. Fatty acid oxidation is how cells break down fats to generate energy, which is particularly important for heart and muscle function, and during periods of fasting.

The SCAD enzyme focuses on metabolising short-chain fatty acids, which are obtained from certain foods or as by-products of breaking down larger fats. Proper function of the ACADS gene is therefore essential for maintaining the body's energy supply from these specific fat sources.

What the gene does

The ACADS gene directs the synthesis of short-chain acyl-CoA dehydrogenase (SCAD), an enzyme located in the mitochondria of cells. Mitochondria are often referred to as the 'powerhouses' of the cell because they are responsible for generating most of the cell's energy in the form of adenosine triphosphate (ATP).

SCAD is a key enzyme in the fatty acid oxidation pathway. This multi-step process breaks down various types of fats into energy. Specifically, SCAD is required for the metabolism of short-chain fatty acids. These fatty acids serve as a significant energy source for tissues like the heart and muscles. During times when food intake is limited, such as fasting, fatty acids also become a critical energy source for the liver and other bodily tissues. The enzyme ensures that these particular fats can be efficiently converted into energy to fuel cellular processes.

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Chromosome location

The ACADS gene is located on chromosome 12 at position 12q24.31. This describes its specific band location on the long arm (q) of chromosome 12. Humans typically have two copies of chromosome 12, inheriting one from each parent.

Protein structure

The ACADS gene produces a protein that is 412 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants in the ACADS gene can alter the function of the SCAD enzyme. These genetic changes can range from single base-pair substitutions to larger alterations that affect the enzyme's ability to properly metabolise short-chain fatty acids. Over 55 different variants in the ACADS gene have been identified.

495
Total variants catalogued in ClinVar
View all on ClinVar →
93 Pathogenic / Likely pathogenic 204 Uncertain significance 158 Benign / Likely benign 40 Conflicting or other

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.1031A>G
single nucleotide variant
 p.Glu344Gly Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.1058C>T
single nucleotide variant
 p.Ser353Leu Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.1095G>T
single nucleotide variant
 p.Gln365His Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1138C>T
single nucleotide variant
 p.Arg380Trp Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.1147C>T
single nucleotide variant
 p.Arg383Cys Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.1192C>T
single nucleotide variant
 p.Gln398Ter Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.125_135del
Deletion
 p.Leu42fs Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.136C>T
single nucleotide variant
 p.Arg46Trp Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.164C>T
single nucleotide variant
 p.Pro55Leu Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-CoA dehydrogenase
c.1A>G
single nucleotide variant
 p.Met1Val Pathogenic/Likely pathogenic ★★☆☆ Deficiency of butyryl-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

Pathogenic variants in the ACADS gene are associated with an inherited metabolic disorder known as short-chain acyl-CoA dehydrogenase deficiency. This condition arises when the SCAD enzyme is unable to function correctly, leading to an accumulation of short-chain fatty acids that cannot be converted into energy.

  • Short-chain acyl-CoA dehydrogenase deficiency
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Inheritance pattern

Conditions caused by pathogenic ACADS variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ACADS carrier status across ancestry groups?

UK clinical status

The ACADS gene is recognised within the NHS Genomic Medicine Service. It is listed on several NHS England National Genomic Test Directory panels, including DDG2P, Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders, all with a 'green' classification indicating strong evidence for gene-disease association.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Likely inborn error of metabolism · R98 NHS GMS → DDG2P NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the ACADS gene?

The ACADS gene provides instructions for making the short-chain acyl-CoA dehydrogenase (SCAD) enzyme. This enzyme is essential for breaking down short-chain fatty acids into energy within the body's cells.

What happens if the ACADS gene does not work correctly?

If the ACADS gene has pathogenic variants, the SCAD enzyme may not function properly. This can lead to short-chain acyl-CoA dehydrogenase deficiency, where the body cannot efficiently convert certain fats into energy.

Where in the cell does the SCAD enzyme function?

The SCAD enzyme, produced from the ACADS gene, primarily functions within the mitochondria. These are organelles often called the 'powerhouses' of the cell, responsible for generating most of the cell's energy.

References

  1. Schmidt SP, Corydon TJ, Pedersen CB. Toxic response caused by a misfolding variant of the mitochondrial protein short-chain acyl-CoA dehydrogenase. Journal of inherited metabolic disease. 2011. PMID: 21170680
  2. Kim SH, Park HD, Sohn YB. Mutations of ACADS gene associated with short-chain acyl-coenzyme A dehydrogenase deficiency. Annals of clinical and laboratory science. 2011. PMID: 21325261
  3. Schmidt SP, Corydon TJ, Pedersen CB. Misfolding of short-chain acyl-CoA dehydrogenase leads to mitochondrial fission and oxidative stress. Molecular genetics and metabolism. 2010. PMID: 20371198
  4. Shirao K, Okada S, Tajima G. Molecular pathogenesis of a novel mutation, G108D, in short-chain acyl-CoA dehydrogenase identified in subjects with short-chain acyl-CoA dehydrogenase deficiency. Human genetics. 2010. PMID: 20376488
  5. Pedersen CB, Kølvraa S, Kølvraa A. The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level. Human genetics. 2008. PMID: 18523805
  6. Jethva R, Bennett MJ, Vockley J. Short-chain acyl-coenzyme A dehydrogenase deficiency. Molecular genetics and metabolism. 2008. PMID: 18977676
  7. van Maldegem BT, Waterham HR, Duran M. The 625G>A SCAD gene variant is common but not associated with increased C4-carnitine in newborn blood spots. Journal of inherited metabolic disease. 2005. PMID: 15902559
  8. Nagan N, Kruckeberg KE, Tauscher AL. The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C(4)-acylcarnitine concentration in newborn blood spots. Molecular genetics and metabolism. 2003. PMID: 12706374
  9. Young SP, Matern D, Gregersen N. A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency. Clinica chimica acta; international journal of clinical chemistry. 2003. PMID: 14568186
  10. Gregersen N, Andresen BS, Corydon MJ. Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship. Human mutation. 2001. PMID: 11524729
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 20 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .