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IVD

isovaleryl-CoA dehydrogenase

The IVD gene provides instructions for producing the isovaleryl-CoA dehydrogenase enzyme, which is critical for processing the amino acid leucine. The IVD gene encodes the isovaleryl-CoA dehydrogenase enzyme, an essential component of protein metabolism.

Chromosome 15q15.1 Autosomal recessive HGNC:6186 Tier C
IVD 15q15.1 p arm q arm 15

IVD is located on the long (q) arm of chromosome 15, at band 15q15.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 15 in the library →

Available at Jeen Health

Clinical tests that include this

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

Overview

The IVD gene is responsible for creating isovaleryl-CoA dehydrogenase, an enzyme crucial for the body's metabolic pathways. This enzyme plays a key role in processing dietary proteins, specifically the amino acid leucine. Proper function of the IVD gene is therefore vital for cellular energy production and overall development.

What the gene does

The isovaleryl-CoA dehydrogenase enzyme, encoded by the IVD gene, is located within the mitochondria of cells. Mitochondria are often referred to as the 'powerhouses' of the cell, converting energy from food into a usable form. The IVD enzyme specifically participates in the third step of leucine breakdown, transforming isovaleryl-CoA into 3-methylcrotonyl-CoA. This conversion is a critical part of the metabolic cascade that ultimately provides energy from leucine processing. Without a functional IVD enzyme, this pathway is disrupted, leading to the build-up of certain metabolic byproducts.

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Chromosome location

The IVD gene is situated on chromosome 15 at position 15q15.1. This specific chromosomal location helps to define where the genetic instructions for the isovaleryl-CoA dehydrogenase enzyme are stored within the human genome.

Protein structure

The IVD protein consists of 426 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations within the IVD gene can affect the function of the isovaleryl-CoA dehydrogenase enzyme. These variants range from those that impair enzyme activity to those that prevent its production entirely. The presence of certain pathogenic variants can disrupt the body's ability to metabolise leucine effectively.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for IVD.
View all on ClinVar →

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.1186G>C
single nucleotide variant
 p.Asp396His Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.1201G>T
single nucleotide variant
 p.Glu401Ter Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.144+1G>C
single nucleotide variant
 - Pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.163A>T
single nucleotide variant
 p.Lys55Ter Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.506_507insT
Insertion
 p.Gly170fs Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.585G>A
single nucleotide variant
 p.Trp195Ter Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.631A>G
single nucleotide variant
 p.Thr211Ala Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.667dup
Duplication
 p.Thr223fs Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.782del
Deletion
 p.Pro261fs Pathogenic/Likely pathogenic ★★☆☆ Isovaleryl-CoA dehydrogenase deficiency
c.879-2A>G
single nucleotide variant
 - Pathogenic ★★☆☆ Isovaleryl-CoA 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

Pathogenic variants in the IVD gene are primarily associated with Isovaleric Acidaemia. This inherited metabolic disorder results from the body's inability to properly break down leucine, leading to the accumulation of toxic byproducts. Approximately 100 different variants in the IVD gene have been identified in individuals with Isovaleric Acidaemia.

Inheritance pattern

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

UK clinical status

The IVD gene is included in several NHS England Genomic Medicine Service national test panels. It is listed with a 'green' status on panels for Isovaleric Acidaemia - Diagnostic (R450), Hyperammonaemia, Intellectual disability, Ketotic hypoglycaemia, Likely inborn error of metabolism (R98), Structural basal ganglia disorders, and Undiagnosed metabolic disorders, indicating strong evidence for its involvement in these conditions.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Isovaleric acidaemia - Diagnostic · R450 NHS GMS → 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 function of the IVD gene?

The IVD gene provides instructions for making the isovaleryl-CoA dehydrogenase enzyme, which is essential for breaking down the amino acid leucine as part of normal protein metabolism within the body's cells.

What happens if the IVD gene doesn't work correctly?

If the IVD gene has pathogenic variants, the isovaleryl-CoA dehydrogenase enzyme may not function properly or may not be produced at all. This can lead to the accumulation of harmful substances in the body, primarily causing Isovaleric Acidaemia.

What is Isovaleric Acidaemia?

Isovaleric Acidaemia is an inherited metabolic disorder caused by pathogenic variants in the IVD gene. It impairs the body's ability to process the amino acid leucine, leading to a build-up of toxic compounds.

References

  1. Ensenauer R, Fingerhut R, Maier EM. Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns. Clinical chemistry. 2011. PMID: 21335445
  2. Lin WD, Wang CH, Lee CC. Genetic mutation profile of isovaleric acidemia patients in Taiwan. Molecular genetics and metabolism. 2007. PMID: 17027310
  3. Vockley J, Ensenauer R. Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity. American journal of medical genetics. Part C, Seminars in medical genetics. 2006. PMID: 16602101
  4. Ensenauer R, Vockley J, Willard JM. A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. American journal of human genetics. 2004. PMID: 15486829
  5. Vockley J, Rogan PK, Anderson BD. Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene. American journal of human genetics. 2000. PMID: 10677295
  6. Mohsen AW, Anderson BD, Volchenboum SL. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia. Biochemistry. 1998. PMID: 9665741
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 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .