Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

ACAD8

acyl-CoA dehydrogenase family member 8

The ACAD8 gene provides instructions for producing the isobutyryl-CoA dehydrogenase (IBD) enzyme, which is vital for the breakdown of the amino acid valine within the body's cells. ACAD8 plays a critical role in metabolic pathways, particularly in mitochondria where it assists in processing proteins from food.

Chromosome 11q25 HGNC:87 Tier C
ACAD8 11q25 p arm q arm 11

ACAD8 is located on the long (q) arm of chromosome 11, at band 11q25. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 11 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
ACAD8 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
ACAD8 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The ACAD8 gene, also known as acyl-CoA dehydrogenase family member 8, is essential for metabolic processes within human cells. It encodes an enzyme that participates in the breakdown of amino acids, which are the building blocks of proteins. This metabolic function is crucial for cellular energy production and overall physiological balance.

Dysfunction of the ACAD8 gene can lead to specific inherited metabolic conditions due to impaired processing of certain amino acids. Research into ACAD8 helps to further understand the complex mechanisms of human metabolism and the genetic basis of metabolic disorders.

What the gene does

The ACAD8 gene directs the synthesis of an enzyme called isobutyryl-CoA dehydrogenase (IBD). This enzyme is primarily located in the mitochondria, which are often referred to as the 'powerhouses' of the cell, responsible for generating energy.

The IBD enzyme plays a specific role in the catabolism of proteins obtained from diet. More precisely, it is involved in the third stage of breaking down valine, an essential amino acid. The enzyme facilitates the conversion of isobutyryl-CoA into methacrylyl-CoA. Subsequently, other enzymes further process methacrylyl-CoA into compounds that cells can utilise for energy, highlighting ACAD8's integral role in cellular energy metabolism.

Video: Genetics 101

Chromosome location

The ACAD8 gene is situated on chromosome 11, specifically at position 11q25. This chromosomal location indicates where the gene resides within the human genome. The precise location on chromosome 11 helps in mapping and understanding the genetic context of ACAD8-related conditions.

Protein structure

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

Key variants

Variants within the ACAD8 gene can lead to alterations in the structure or function of the isobutyryl-CoA dehydrogenase enzyme. These genetic changes can impair the enzyme's ability to effectively break down valine, an essential amino acid. The clinical impact of ACAD8 variants can vary considerably among individuals.

304
Total variants catalogued in ClinVar
View all on ClinVar →
37 Pathogenic / Likely pathogenic 139 Uncertain significance 104 Benign / Likely benign 24 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.1129G>A
single nucleotide variant
 p.Gly377Ser Pathogenic/Likely pathogenic ★★☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.286G>A
single nucleotide variant
 p.Gly96Ser Pathogenic ★★☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.2T>C
single nucleotide variant
 p.Met1Thr Pathogenic/Likely pathogenic ★★☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.384G>A
single nucleotide variant
 p.Met128Ile Pathogenic/Likely pathogenic ★★☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.616C>T
single nucleotide variant
 p.Arg206Ter Pathogenic ★★☆☆ Inborn genetic diseases
c.886C>T
single nucleotide variant
 p.Arg296Ter Pathogenic ★★☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.1000C>T
single nucleotide variant
 p.Arg334Cys Pathogenic ★☆☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.1092+1G>A
single nucleotide variant
 - Pathogenic ★☆☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.1092+1G>C
single nucleotide variant
 - Pathogenic ★☆☆☆ Deficiency of isobutyryl-CoA dehydrogenase
c.1176G>T
single nucleotide variant
 p.Arg392Ser Pathogenic ★☆☆☆ Inborn genetic diseases

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 ACAD8 gene are associated with isobutyryl-CoA dehydrogenase deficiency. This condition arises when the body cannot properly metabolise valine, an amino acid, due to insufficient or non-functional IBD enzyme. While some individuals with this deficiency may experience symptoms, many are asymptomatic, or the condition presents with varying degrees of severity.

No disease links recorded for this gene in our reference set.

UK clinical status

The ACAD8 gene is included in certain NHS Genomic Medicine Service panels, indicating its clinical relevance in the UK. It is listed on the 'Likely inborn error of metabolism' and 'Undiagnosed metabolic disorders' green panels in NHS England's PanelApp, suggesting it is considered of high diagnostic utility for 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 →
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 ACAD8 gene?

The ACAD8 gene provides instructions for creating the isobutyryl-CoA dehydrogenase (IBD) enzyme, which is crucial for the breakdown of the amino acid valine in the mitochondria, contributing to cellular energy production.

What condition is associated with ACAD8 gene variants?

Variants in the ACAD8 gene are linked to isobutyryl-CoA dehydrogenase deficiency. This metabolic disorder impairs the body's ability to properly process valine.

Is ACAD8 relevant for NHS clinical testing?

Yes, ACAD8 is featured on specific NHS England's PanelApp green panels, including 'Likely inborn error of metabolism' and 'Undiagnosed metabolic disorders,' indicating its importance in diagnostic screening for these conditions.

References

  1. Oglesbee D, He M, Majumder N. Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genetics in medicine : official journal of the American College of Medical Genetics. 2007. PMID: 17304052
  2. Pedersen CB, Bischoff C, Christensen E. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening. Pediatric research. 2006. PMID: 16857760
  3. Koeberl DD, Young SP, Gregersen NS. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatric research. 2003. PMID: 12736383
  4. Nguyen TV, Andresen BS, Corydon TJ. Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans. Molecular genetics and metabolism. 2002. PMID: 12359132
  5. Roe CR, Cederbaum SD, Roe DS. Isolated isobutyryl-CoA dehydrogenase deficiency: an unrecognized defect in human valine metabolism. Molecular genetics and metabolism. 1998. PMID: 9889013
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 .