U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

IVD isovaleryl-CoA dehydrogenase [ Homo sapiens (human) ]

Gene ID: 3712, updated on 11-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
IVDprovided by HGNC
Official Full Name
isovaleryl-CoA dehydrogenaseprovided by HGNC
Primary source
HGNC:HGNC:6186
See related
Ensembl:ENSG00000128928 MIM:607036; AllianceGenome:HGNC:6186
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IVDH; ACAD2
Summary
Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial matrix enzyme that catalyzes the third step in leucine catabolism. The genetic deficiency of IVD results in an accumulation of isovaleric acid, which is toxic to the central nervous system and leads to isovaleric acidemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
Expression
Ubiquitous expression in thyroid (RPKM 25.0), liver (RPKM 18.5) and 24 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
15q15.1
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (40405795..40435947)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (38212996..38243333)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40697996..40728146)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903472 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40655530-40656030 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40656031-40656531 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40659527-40660418 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6330 Neighboring gene dispatched RND transporter family member 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40673800-40674300 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40674955-40675478 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40675479-40676000 Neighboring gene kinetochore localized astrin (SPAG5) binding protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9241 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9242 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40699201-40699700 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40728630-40729168 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40729169-40729706 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40731858-40732395 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40733201-40733702 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40733703-40734202 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6333 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6334 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40737995-40738496 Neighboring gene bromo adjacent homology domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9243 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9244 Neighboring gene uncharacterized LOC124903473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40755909-40756410 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40756411-40756910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9245 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6335 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6336 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40764047-40764950 Neighboring gene carbohydrate sulfotransferase 14

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia. Couce ML, et al. J Hum Genet, 2017 Mar. PMID 27904153
  2. Phenotypic Variability and Newly Identified Mutations of the IVD Gene in Japanese Patients with Isovaleric Acidemia. Sakamoto O, et al. Tohoku J Exp Med, 2015 Jun. PMID 26018748
  3. Kinetic and spectral properties of isovaleryl-CoA dehydrogenase and interaction with ligands. Mohsen AW, et al. Biochimie, 2015 Jan. PMID 25450250, Free PMC Article
  4. Identification of a novel IVD mutation in a consanguineous family with isovaleric acidemia. Kaya N, et al. Gene, 2013 Jan 25. PMID 23063737
  5. Clinical and molecular analysis of isovaleric acidemia patients in the United Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD gene. Hertecant JL, et al. Eur J Med Genet, 2012 Dec. PMID 22960500

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A Case Report of a Novel Isovaleryl-CoA Dehydrogenase Gene Mutation in a Chinese Family with Isovaleric Acidemia.
    Title: A Case Report of a Novel Isovaleryl-CoA Dehydrogenase Gene Mutation in a Chinese Family with Isovaleric Acidemia.
  2. Nine novel isovaleryl-CoA dehydrogenase mutations have been found in a Spanish cohort with isovaleric acidemia.
    Title: Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia.
  3. Our results have illustrated the heterogeneous mutation spectrum and clinical presentation of IVA in the Japanese patients
    Title: Phenotypic Variability and Newly Identified Mutations of the IVD Gene in Japanese Patients with Isovaleric Acidemia.
  4. kinetics and ligand binding of isovaleryl-CoA dehydrogenase
    Title: Kinetic and spectral properties of isovaleryl-CoA dehydrogenase and interaction with ligands.
  5. study reports the first Saudi isovaleric acidemia patients from a consanguineous family with a novel transversion (p.G362V) and briefly discuss likely phenotype-genotype correlation of the disease in the Saudi population
    Title: Identification of a novel IVD mutation in a consanguineous family with isovaleric acidemia.
  6. A heterogeneous mutation spectrum in the IVD gene was identified in isovaleric acidemia patients in the United Arab Emirates.
    Title: Clinical and molecular analysis of isovaleric acidemia patients in the United Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD gene.
  7. All were homozygous for a single c.367 G > A (p.G123R) mutation. Despite the genetic homogeneity of this South African group, the clinical presentation varied, ranging from mental handicap and episodes of metabolic derangement to an asymptomatic state
    Title: Clinical variability of isovaleric acidemia in a genetically homogeneous population.
  8. A child with isovaleric acidemia was subsequently found to harbour a known missense mutation (c.A1199G [p.Y371C]) and a novel 4-bp duplication (c.1148_1151dupGCTA [p.Y355X]) in the IVD gene. The former may be a founder mutation in the Chinese population.
    Title: A novel duplication at the putative DNA polymerase alpha arrest site and a founder mutation in Chinese in the IVD gene underlie isovaleric acidaemia.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  10. Mutations of isovaleryl-CoA dehydrogenase gene is associated with isovaleric acidemia
    Title: Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia.
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Isovaleryl-CoA dehydrogenase deficiency
MedGen: C0268575 OMIM: 243500 GeneReviews: Classic Isovaleric Acidemia
Compare labs

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis.
EBI GWAS Catalog
Human metabolic individuality in biomedical and pharmaceutical research.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ12715, FLJ34849

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables butyryl-CoA dehydrogenase activity IEA
Inferred from Electronic Annotation
more info
  
enables flavin adenine dinucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables isovaleryl-CoA dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables isovaleryl-CoA dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables isovaleryl-CoA dehydrogenase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in L-leucine catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in L-leucine catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in L-leucine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in L-leucine catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in branched-chain amino acid catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in fatty acid beta-oxidation using acyl-CoA dehydrogenase IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in mitochondrial matrix ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

Go to the top of the page Help
Preferred Names
isovaleryl-CoA dehydrogenase, mitochondrial
Names
butyryl-CoA dehydrogenase
epididymis secretory sperm binding protein
isovaleryl Coenzyme A dehydrogenase
NP_001152980.2
NP_001341526.1
NP_001341527.2
NP_001341528.2
NP_001341529.2
NP_001341530.2
NP_002216.3
XP_006720558.1
XP_016877638.1
XP_016877642.1
XP_016877643.1
XP_016877644.1
XP_016877646.1
XP_016877647.1
XP_047288416.1
XP_047288417.1
XP_047288418.1
XP_047288419.1
XP_047288420.1
XP_054233827.1
XP_054233828.1
XP_054233829.1
XP_054233830.1
XP_054233831.1
XP_054233832.1
XP_054233833.1
XP_054233834.1
XP_054233835.1
XP_054233836.1
XP_054233837.1
XP_054233838.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011986.2 RefSeqGene

    Range
    5311..20824
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001159508.3 → NP_001152980.2  isovaleryl-CoA dehydrogenase, mitochondrial isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame coding exon in the 5' coding region compared to variant 1. The resulting shorter isoform (2) lacks an internal protein segment compared to isoform 1.
    Source sequence(s)
    AC013356, AK122922
    Consensus CDS
    CCDS53930.2
    UniProtKB/TrEMBL
    A0A0S2Z4K7, A0A384MR53
    Related
    ENSP00000417990.3, ENST00000479013.7
    Conserved Domains (1) summary
    cd01156
    Location:17 → 390
    IVD; Isovaleryl-CoA dehydrogenase

  2. NM_001354597.3 → NP_001341526.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate 5' terminal exon and uses an alternate, in-frame translation start codon compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC013356, AI086669, AK122922, AK315296
    UniProtKB/TrEMBL
    A0A384MR53
    Conserved Domains (1) summary
    cd01156
    Location:26 → 404
    IVD; Isovaleryl-CoA dehydrogenase

  3. NM_001354598.3 → NP_001341527.2  isovaleryl-CoA dehydrogenase, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains two alternate exons in the 3' region compared to variant 1. The resulting isoform (4) has a longer and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC013356, AK315296
    UniProtKB/TrEMBL
    A0A384MR53
    Conserved Domains (1) summary
    cd01156
    Location:41 → 380
    IVD; Isovaleryl-CoA dehydrogenase

  4. NM_001354599.3 → NP_001341528.2  isovaleryl-CoA dehydrogenase, mitochondrial isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate, in-frame donor splice site in the 5' coding region compared to variant 1. The resulting longer isoform (5) contains an internal protein segment not found in isoform 1.
    Source sequence(s)
    AC013356, AI086669, AK122922, AK315296, BG714533
    UniProtKB/TrEMBL
    A0A384MR53
    Conserved Domains (1) summary
    cd01156
    Location:41 → 449
    IVD; Isovaleryl-CoA dehydrogenase

  5. NM_001354600.3 → NP_001341529.2  isovaleryl-CoA dehydrogenase, mitochondrial isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) uses an alternate, in-frame donor splice site in the 5' coding region and contains two alternate exons in the 3' region compared to variant 1. The resulting longer isoform (6) contains an internal protein segment in the 5' coding region, and has a longer and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC013356, AK315296, BG714533
    UniProtKB/TrEMBL
    A0A384MR53
    Conserved Domains (1) summary
    cd01156
    Location:41 → 409
    IVD; Isovaleryl-CoA dehydrogenase

  6. NM_001354601.3 → NP_001341530.2  isovaleryl-CoA dehydrogenase, mitochondrial isoform 7

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) contains an alternate 3' terminal exon compared to variant 1. The resulting isoform (7) has a longer and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC013356, AK315296
    Conserved Domains (1) summary
    cd01156
    Location:41 → 380
    IVD; Isovaleryl-CoA dehydrogenase

  7. NM_002225.5 → NP_002216.3  isovaleryl-CoA dehydrogenase, mitochondrial isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1.
    Source sequence(s)
    AC013356, AI086669, AK315296
    Consensus CDS
    CCDS10057.3
    UniProtKB/TrEMBL
    A0A0A0MT83, A0A0S2Z422, A0A384MR53
    Related
    ENSP00000418397.3, ENST00000487418.8
    Conserved Domains (1) summary
    cd01156
    Location:41 → 420
    IVD; Isovaleryl-CoA dehydrogenase

RNA

  1. NR_148925.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10) contains an alternate 5' terminal exon, and several alternate exons in the 3' region compared to variant 1. It is represented as non-coding because the use of an alternate, in-frame 5'-most translation start codon as used in variant 3, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC013356, KF459687

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    40405795..40435947
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047432460.1 → XP_047288416.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X2

  2. XM_047432461.1 → XP_047288417.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X3

  3. XM_017022149.2 → XP_016877638.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X1

  4. XM_017022153.2 → XP_016877642.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X4

    UniProtKB/Swiss-Prot
    B2RCV5, B3KVI7, J3KR54, P26440, Q53XZ9, Q96AF6
    UniProtKB/TrEMBL
    A0A2L0RIE3

  5. XM_017022157.2 → XP_016877646.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X9

  6. XM_047432462.1 → XP_047288418.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X7

  7. XM_006720495.4 → XP_006720558.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X11

    Conserved Domains (1) summary
    cl09933
    Location:44 → 323
    ACAD; Acyl-CoA dehydrogenase

  8. XM_017022154.3 → XP_016877643.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X5

    UniProtKB/TrEMBL
    A0A384MR53

  9. XM_047432464.1 → XP_047288420.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X10

  10. XM_017022155.3 → XP_016877644.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X6

    UniProtKB/Swiss-Prot
    B2RCV5, B3KVI7, J3KR54, P26440, Q53XZ9, Q96AF6
    UniProtKB/TrEMBL
    A0A2L0RIE3
    Conserved Domains (1) summary
    cd01156
    Location:44 → 411
    IVD; Isovaleryl-CoA dehydrogenase

  11. XM_047432463.1 → XP_047288419.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X8

  12. XM_017022158.3 → XP_016877647.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X12

RNA

  1. XR_007064441.1 RNA Sequence

  2. XR_007064442.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    38212996..38243333
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054377852.1 → XP_054233827.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X1

  2. XM_054377855.1 → XP_054233830.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X4

  3. XM_054377860.1 → XP_054233835.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X9

  4. XM_054377858.1 → XP_054233833.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X7

  5. XM_054377862.1 → XP_054233837.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X11

  6. XM_054377857.1 → XP_054233832.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X6

  7. XM_054377859.1 → XP_054233834.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X8

  8. XM_054377863.1 → XP_054233838.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X12

  9. XM_054377853.1 → XP_054233828.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X2

  10. XM_054377854.1 → XP_054233829.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X3

  11. XM_054377856.1 → XP_054233831.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X5

  12. XM_054377861.1 → XP_054233836.1  isovaleryl-CoA dehydrogenase, mitochondrial isoform X10

RNA

  1. XR_008488942.1 RNA Sequence

  2. XR_008488943.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NR_148923.1: Suppressed sequence

    Description
    NR_148923.1: This RefSeq was removed because it represents an allelic variant that lacks a short repeat (rs368025013), rather than a splice variant.

  2. NR_148924.1: Suppressed sequence

    Description
    NR_148924.1: This RefSeq was removed because it represents an allelic variant that lacks a short repeat (rs368025013), rather than a splice variant.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P26440.2 GenPept UniProtKB/Swiss-Prot:P26440

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous