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ACADM

acyl-CoA dehydrogenase medium chain

The ACADM gene provides instructions for producing medium-chain acyl-CoA dehydrogenase (MCAD), an enzyme vital for breaking down fats into energy within cells. ACADM is essential for fatty acid oxidation, a process that converts fats into usable energy, particularly for the heart, muscles, and during fasting.

Chromosome 1p31.1 Autosomal recessive HGNC:89 Tier C
ACADM 1p31.1 p arm q arm 1

ACADM is located on the short (p) arm of chromosome 1, at band 1p31.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

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Clinical tests that include this

Carrier Screening panel
ACADM is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
ACADM is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The ACADM gene codes for the enzyme medium-chain acyl-CoA dehydrogenase (MCAD), which plays a critical role in cellular energy production. This enzyme is primarily active within mitochondria, the powerhouses of the cell, where it facilitates the breakdown of medium-chain fatty acids.

Efficient metabolism of these fats is crucial for maintaining energy levels, especially for organs like the heart and muscles, and during periods when the body relies on fat stores for fuel, such as fasting.

What the gene does

The ACADM gene produces the medium-chain acyl-CoA dehydrogenase (MCAD) enzyme, which is integral to fatty acid oxidation. This multi-step metabolic pathway breaks down fats to generate energy for the body.

Specifically, MCAD is responsible for metabolising medium-chain fatty acids, which are derived from dietary sources, body fat, and the breakdown of larger fatty acids. These fatty acids represent a significant energy source for muscle tissues and the heart. During times of food deprivation, fatty acids become an essential energy supply for the liver and other tissues, highlighting the enzyme's importance in metabolic homeostasis.

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Chromosome location

The ACADM gene is located on the short arm of chromosome 1 at position 31.1, denoted as 1p31.1. This specific chromosomal band houses the genetic instructions for the MCAD enzyme.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Over 80 different genetic changes, or variants, in the ACADM gene have been identified. Many of these involve a single alteration in the protein's building blocks, known as amino acids. Such variants can impact the function of the MCAD enzyme, potentially leading to reduced activity or complete loss of function.

1,059
Total variants catalogued in ClinVar
View all on ClinVar →
374 Pathogenic / Likely pathogenic 258 Uncertain significance 361 Benign / Likely benign 66 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.1010A>C
single nucleotide variant
 p.Tyr337Ser Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1012C>T
single nucleotide variant
 p.Gln338Ter Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1034A>T
single nucleotide variant
 p.Asp345Val Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1040G>T
single nucleotide variant
 p.Gly347Val Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1042C>T
single nucleotide variant
 p.Arg348Cys Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1042del
Deletion
 p.Arg348fs Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1045C>T
single nucleotide variant
 p.Arg349Ter Pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1046G>A
single nucleotide variant
 p.Arg349Gln Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1049_1055dup
Duplication
 p.Tyr352Ter Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A dehydrogenase deficiency
c.1237C>A
single nucleotide variant
 p.Arg413Ser Pathogenic/Likely pathogenic ★★☆☆ Medium-chain acyl-coenzyme A 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

Variants within the ACADM gene are primarily associated with inherited metabolic disorders. The most notable condition linked to this gene is Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), an autosomal recessive disorder. Atypical forms of MCADD have also been described.

  • MCADD (atypical)
    IEM
    AR
  • Medium-chain acyl-CoA dehydrogenase deficiency
    IEM
    AR
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Inheritance pattern

Conditions caused by pathogenic ACADM 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 ACADM carrier status across ancestry groups?

UK clinical status

The ACADM gene is recognised within several NHS Genomic Medicine Service national panels. It is listed as 'green' on PanelApp for conditions such as Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) - Diagnostic, Acute rhabdomyolysis, Hyperammonaemia, Intellectual disability, Likely inborn error of metabolism, Rhabdomyolysis and metabolic muscle disorders, and Undiagnosed metabolic disorders, indicating strong evidence for its gene-disease association in these contexts.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Acute rhabdomyolysis · R419 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) - Diagnostic · R451 NHS GMS → DDG2P NHS GMS → Intellectual disability NHS GMS → Rhabdomyolysis and metabolic muscle disorders 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 function of the ACADM gene?

The ACADM gene provides instructions for creating the MCAD enzyme, which is crucial for breaking down medium-chain fatty acids into energy. This process is vital for the heart, muscles, and for energy supply during fasting.

What is Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)?

MCADD is an inherited metabolic disorder caused by changes in the ACADM gene. It affects the body's ability to convert certain fats into energy, which can lead to serious health issues if not managed.

How is MCADD inherited?

MCADD is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a pathogenic variant, one from each parent, to develop the condition. Individuals with one pathogenic variant are typically carriers and do not show symptoms.

References

  1. Maier EM, Gersting SW, Kemter KF. Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening. Human molecular genetics. 2009. PMID: 19224950
  2. Hsu HW, Zytkovicz TH, Comeau AM. Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening. Pediatrics. 2008. PMID: 18450854
  3. Waddell L, Wiley V, Carpenter K. Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations. Molecular genetics and metabolism. 2006. PMID: 16291504
  4. Maier EM, Liebl B, Röschinger W. Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Human mutation. 2005. PMID: 15832312
  5. 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
  6. Wang SS, Fernhoff PM, Hannon WH. Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. Genetics in medicine : official journal of the American College of Medical Genetics. 1999. PMID: 11263545
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 6 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .