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    ACAD9 acyl-CoA dehydrogenase family member 9 [ Homo sapiens (human) ]

    Gene ID: 28976, updated on 7-Apr-2024

    Summary

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    Official Symbol
    ACAD9provided by HGNC
    Official Full Name
    acyl-CoA dehydrogenase family member 9provided by HGNC
    Primary source
    HGNC:HGNC:21497
    See related
    Ensembl:ENSG00000177646 MIM:611103; AllianceGenome:HGNC:21497
    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
    NPD002; MC1DN20
    Summary
    This gene encodes a member of the acyl-CoA dehydrogenase family. Members of this family of proteins localize to the mitochondria and catalyze the rate-limiting step in the beta-oxidation of fatty acyl-CoA. The encoded protein is specifically active toward palmitoyl-CoA and long-chain unsaturated substrates. Mutations in this gene cause acyl-CoA dehydrogenase family member type 9 deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]
    Expression
    Ubiquitous expression in skin (RPKM 14.5), fat (RPKM 6.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3q21.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (128879620..128913114)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (131624340..131657836)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (128598463..128631957)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:128583050-128583876 Neighboring gene IFT122 pseudogene 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:128597333-128598184 and GRCh37_chr3:128598185-128599037 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:128599038-128599889 Neighboring gene ACAD9 divergent transcript Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:128620937-128622136 Neighboring gene cilia and flagella associated protein 92 (putative) Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:128651057-128651558 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128653559-128654060 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128654061-128654560 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:128682980-128683974 Neighboring gene MPRA-validated peak4825 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:128705779-128706978 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128711587-128712348 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14714 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128734769-128735276 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128735847-128736348 Neighboring gene EF-hand and coiled-coil domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14716 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128752375-128752929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128756987-128757962 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:128757963-128758936 Neighboring gene JMJD4 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients. Dewulf JP, et al. Mol Genet Metab, 2016 Jul. PMID 27233227
    2. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules. Leslie N, et al. Hum Pathol, 2016 Mar. PMID 26826406
    3. High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood. Collet M, et al. Eur J Hum Genet, 2016 Aug. PMID 26669660, Free PMC Article
    4. ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. Nouws J, et al. Hum Mol Genet, 2014 Mar 1. PMID 24158852
    5. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Haack TB, et al. Nat Genet, 2010 Dec. PMID 21057504

    See all (87) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A).
      Title: Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A).
    2. Mutations in the ND6, NDUFV1 or ACAD9 genes are responsible for the mitochondrial complex I deficiency.
      Title: Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum-mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients with complex I deficiency.
    3. Study identified new mutations in ACAD9 responsible for a wide spectrum of heart diseases in the presence of elevated serum lactate levels.
      Title: Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients.
    4. ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency.
      Title: High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.
    5. Case Report: neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.
      Title: Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.
    6. In cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation.
      Title: Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency.
    7. Our results underscore the importance of the ACAD9 protein in complex I assembly and suggest that the enzymatic activity is a rudiment of the duplication event.
      Title: ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies.
    8. Strong candidate gene for mitochondrial disease, based on recessive mutations detected in infantile patients
      Title: Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.
    9. Our data support a new function for ACAD9 in complex I function, making this gene an important new candidate for patients with complex I deficiency, which could be improved by riboflavin treatment.
      Title: Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.
    10. ACAD9 screening of 120 additional complex I-defective index cases led us to identify two additional unrelated cases and a total of five pathogenic ACAD9 alleles.
      Title: Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Phenotypes

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    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
    Acyl-CoA dehydrogenase 9 deficiency
    MedGen: C4747517 OMIM: 611126 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    GWAS of dental caries patterns in the permanent dentition.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23533, MGC14452

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables acyl-CoA dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables flavin adenine dinucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables long-chain fatty acyl-CoA dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables medium-chain fatty acyl-CoA dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in long-chain fatty acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in medium-chain fatty acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial respiratory chain complex I assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial respiratory chain complex I assembly NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in dendrite IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    complex I assembly factor ACAD9, mitochondrial
    Names
    acyl-Coenzyme A dehydrogenase family, member 9
    very-long-chain acyl-CoA dehydrogenase VLCAD
    NP_001397734.1
    NP_054768.2
    XP_024309252.1
    XP_054202337.1

    NCBI Reference Sequences (RefSeq)

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    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_017064.1 RefSeqGene

      Range
      5131..38625
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001410805.1 → NP_001397734.1  complex I assembly factor ACAD9, mitochondrial isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC112484
      Consensus CDS
      CCDS93369.1
      UniProtKB/TrEMBL
      Q9H9W4

    2. NM_014049.5 → NP_054768.2  complex I assembly factor ACAD9, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_054768.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the functional protein.
      Source sequence(s)
      BC007970, BC013354, DA630022
      Consensus CDS
      CCDS3053.1
      UniProtKB/Swiss-Prot
      D3DNB8, Q8WXX3, Q9H845
      UniProtKB/TrEMBL
      A0A7P0T8U3
      Related
      ENSP00000312618.7, ENST00000308982.12
      Conserved Domains (1) summary
      cd01161
      Location:38 → 445
      VLCAD; Very long chain acyl-CoA dehydrogenase

    RNA

    1. NR_033426.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an addition segment in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK297952, BC007970, DA630022
      Related
      ENST00000511227.5

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      128879620..128913114
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024453484.2 → XP_024309252.1  complex I assembly factor ACAD9, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q9H9W4
      Related
      ENSP00000506228.1, ENST00000679715.1
      Conserved Domains (1) summary
      cl09933
      Location:1 → 322
      ACAD; Acyl-CoA dehydrogenase

    RNA

    1. XR_427367.4 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      131624340..131657836
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054346362.1 → XP_054202337.1  complex I assembly factor ACAD9, mitochondrial isoform X1

    RNA

    1. XR_008486706.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H845.1 GenPept UniProtKB/Swiss-Prot:Q9H845

    Gene LinkOut

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

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