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ACADS

acyl-CoA dehydrogenase short chain

The ACADS gene provides instructions for producing the short-chain acyl-CoA dehydrogenase (SCAD) enzyme, which is vital for breaking down short-chain fatty acids into energy within cells. The ACADS gene is responsible for encoding the SCAD enzyme, a key component in the mitochondrial process of fatty acid oxidation.

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.

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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, or acyl-CoA dehydrogenase short chain, plays a critical role in cellular energy production. It provides the genetic blueprint for an enzyme called short-chain acyl-CoA dehydrogenase (SCAD). This enzyme is particularly important in the metabolism of certain fats, ensuring cells have access to vital energy sources, especially during periods of fasting or high energy demand.

Disruptions in the ACADS gene's function can lead to metabolic disorders that affect how the body processes these fats. Understanding the ACADS gene is therefore crucial for diagnosing and managing conditions related to fatty acid metabolism.

What the gene does

The ACADS gene's primary function is to direct the synthesis of the short-chain acyl-CoA dehydrogenase (SCAD) enzyme. This enzyme operates within the mitochondria, which are often referred to as the 'powerhouses' of the cell due to their role in energy generation. SCAD is an essential component of fatty acid oxidation, a multi-step biochemical pathway that breaks down fats into usable energy.

Specifically, SCAD is tasked with metabolising short-chain fatty acids. These fatty acids are consumed in some foods and are also generated during the breakdown of larger fatty acids. Heart and muscle tissues rely heavily on fatty acids for energy. Furthermore, during times when food intake is low, such as fasting, fatty acids become a crucial energy source for organs like the liver and various other tissues throughout the body.

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Chromosome location

The ACADS gene is situated on chromosome 12. Its precise location is mapped to the long (q) arm of chromosome 12, specifically within band 24.31. This genomic address helps in identifying and studying the gene's position relative to other genes on the chromosome.

Protein structure

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

Key variants

Genetic variations within the ACADS gene can influence the function of the short-chain acyl-CoA dehydrogenase enzyme. These variations range from single nucleotide changes to larger deletions or insertions, and can impact the enzyme's structure, stability, or activity. Pathogenic variants are those that disrupt the enzyme's normal function, leading to metabolic challenges.

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

Variants in the ACADS gene are associated with an inherited metabolic disorder called Short-chain acyl-CoA dehydrogenase deficiency. This condition is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to be affected. The deficiency impairs the body's ability to process short-chain fatty acids, leading to their accumulation.

  • 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 UK's NHS Genomic Medicine Service. It is listed on several Green panels in PanelApp, including those for DDG2P, Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders, indicating its established role in these conditions.

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 primary function of the ACADS gene?

The ACADS gene provides instructions for making the short-chain acyl-CoA dehydrogenase (SCAD) enzyme, which is essential for breaking down short-chain fatty acids in the mitochondria to produce energy.

What condition is associated with variants in the ACADS gene?

Pathogenic variants in the ACADS gene are associated with Short-chain acyl-CoA dehydrogenase deficiency, an autosomal recessive metabolic disorder affecting the body's ability to process certain fats.

How is Short-chain acyl-CoA dehydrogenase deficiency inherited?

Short-chain acyl-CoA dehydrogenase deficiency follows an autosomal recessive inheritance pattern. This means an individual must inherit a pathogenic variant from each parent to develop the condition.

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 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .