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    ACSF3 acyl-CoA synthetase family member 3 [ Homo sapiens (human) ]

    Gene ID: 197322, updated on 14-Nov-2024

    Summary

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    Official Symbol
    ACSF3provided by HGNC
    Official Full Name
    acyl-CoA synthetase family member 3provided by HGNC
    Primary source
    HGNC:HGNC:27288
    See related
    Ensembl:ENSG00000176715 MIM:614245; AllianceGenome:HGNC:27288
    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
    Summary
    This gene encodes a member of the acyl-CoA synthetase family of enzymes that activate fatty acids by catalyzing the formation of a thioester linkage between fatty acids and coenzyme A. The encoded protein is localized to mitochondria, has high specificity for malonate and methylmalonate and possesses malonyl-CoA synthetase activity. Mutations in this gene are a cause of combined malonic and methylmalonic aciduria. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Sep 2013]
    Expression
    Ubiquitous expression in duodenum (RPKM 1.5), lymph node (RPKM 1.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ACSF3 in Genome Data Viewer
    Location:
    16q24.3
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (89093852..89156233)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (95173811..95236254)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (89160260..89222641)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11392 Neighboring gene uncharacterized LOC105371412 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89154413-89154912 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7892 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11393 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46375 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11394 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr16:89180375-89181574 Neighboring gene Sharpr-MPRA regulatory region 10518 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89200477-89201376 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46429 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:89226077-89226576 Neighboring gene long intergenic non-protein coding RNA 304 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:89233179-89234027 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:89234028-89234875 Neighboring gene long intergenic non-protein coding RNA 2138

    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 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. Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype. Alfares A, et al. J Med Genet, 2011 Sep. PMID 21785126
    2. The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism. Wehbe Z, et al. Biochim Biophys Acta Mol Cell Biol Lipids, 2019 Nov. PMID 31376476
    3. Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort. Levtova A, et al. J Inherit Metab Dis, 2019 Jan. PMID 30740739
    4. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Bowman CE, et al. Adv Biol Regul, 2019 Jan. PMID 30201289, Free PMC Article
    5. Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Sloan JL, et al. Nat Genet, 2011 Aug 14. PMID 21841779, Free PMC Article

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Causal ACSF3 mutations were identified in all patients.
      Title: Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort.
    2. ACSF3 catalyzes the first step of mitochondrial fatty acid biosynthesis (mtFASII). Hypofunctional mtFASII impairs mitochondrial flexibility and lipoylation degree. Defective mtFASII leads to reduced glycolytic flux and upregulation of beta-oxidation.
      Title: The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism.
    3. ACSF3-derived malonyl-CoA can be used to malonylate lysine residues on proteins within the matrix of mitochondria, possibly adding another regulatory layer to post-translational control of mitochondrial metabolism.
      Title: Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism.
    4. an essential role for ACSF3 in dictating the metabolic fate of mitochondrial malonate and malonyl-CoA in mammalian metabolism
      Title: The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency.
    5. ACSF3 was significantly upregulated, and was involved in fatty acid and lipid metabolism and accelerated liver injury in alcoholic liver disease.
      Title: Analysis of differentially expressed genes and microRNAs in alcoholic liver disease.
    6. data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of immunoglobulin heavy chain translocations, which might contribute to the pathogenesis of pediatric GC-derived B-cell lymphoma.
      Title: The CBFA2T3/ACSF3 locus is recurrently involved in IGH chromosomal translocation t(14;16)(q32;q24) in pediatric B-cell lymphoma with germinal center phenotype.
    7. ACSF3 is a candidate gene for non-classical CMAMMA observed in our patients.
      Title: Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype.
    8. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis.
      Title: Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis.
    9. mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase, were identified as a cause of combined malonic and methylmalonic aciduria.
      Title: Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    Submit: New GeneRIF Correction

    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
    Combined malonic and methylmalonic acidemia
    MedGen: C3280314 OMIM: 614265 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • FLJ39242

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables acid-thiol ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables malonyl-CoA synthetase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables very long-chain fatty acid-CoA ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables very long-chain fatty acid-CoA ligase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in fatty acid biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fatty acid biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fatty acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in long-chain fatty-acyl-CoA biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in malonate catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    malonate--CoA ligase ACSF3, mitochondrial
    Names
    acyl-CoA synthetase family member 3, mitochondrial
    malonyl-CoA synthetase
    NP_001120686.1
    NP_001230208.1
    NP_001271245.1
    NP_777577.2

    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_031961.1 RefSeqGene

      Range
      5044..67425
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001127214.4 → NP_001120686.1  malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_001120686.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1).
      Source sequence(s)
      AC009113, AK290963, BM148793
      Consensus CDS
      CCDS10974.1
      UniProtKB/Swiss-Prot
      A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7
      UniProtKB/TrEMBL
      A0A3B3ISK9
      Related
      ENSP00000384627.3, ENST00000406948.7
      Conserved Domains (1) summary
      cd05941
      Location:55 → 571
      MCS; Malonyl-CoA synthetase (MCS)

    2. NM_001243279.3 → NP_001230208.1  malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_001230208.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1).
      Source sequence(s)
      AC009113, AC135782, BC028399, BM148793
      Consensus CDS
      CCDS10974.1
      UniProtKB/Swiss-Prot
      A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7
      UniProtKB/TrEMBL
      A0A3B3ISK9
      Related
      ENSP00000479130.1, ENST00000614302.5
      Conserved Domains (1) summary
      cd05941
      Location:55 → 571
      MCS; Malonyl-CoA synthetase (MCS)

    3. NM_001284316.2 → NP_001271245.1  malonate--CoA ligase ACSF3, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two exons, one of which contains a portion of the 5' UTR and the other which contains a portion of the 5' coding region including the start codon, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC009113, BI837487, BM148793, BQ953430, BX325026, BX402632
      Consensus CDS
      CCDS73926.1
      UniProtKB/TrEMBL
      F5H5A1, Q6P2C7
      Related
      ENSP00000367596.4, ENST00000378345.8
      Conserved Domains (1) summary
      cl17068
      Location:1 → 306
      AFD_class_I; Adenylate forming domain, Class I superfamily

    4. NM_174917.5 → NP_777577.2  malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_777577.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1, 2 and 4 encode the same isoform (1).
      Source sequence(s)
      AC009113, AC135782, AK075499, DA062861
      Consensus CDS
      CCDS10974.1
      UniProtKB/Swiss-Prot
      A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7
      UniProtKB/TrEMBL
      A0A3B3ISK9
      Related
      ENSP00000320646.4, ENST00000317447.9
      Conserved Domains (1) summary
      cd05941
      Location:55 → 571
      MCS; Malonyl-CoA synthetase (MCS)

    RNA

    1. NR_045667.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC009113, AK075499, AK096561
      Related
      ENST00000537116.5

    2. NR_104293.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses two alternate splice sites, one in the 5' and one in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC009113, AC135782, BC072391, BM148793, BX404035, HY100877

    3. NR_147928.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC009113, AC135782

    4. NR_147929.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC009113, AC135782

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      89093852..89156233
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      95173811..95236254
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_045666.1: Suppressed sequence

      Description
      NR_045666.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q4G176.3 GenPept UniProtKB/Swiss-Prot:Q4G176

    Gene LinkOut

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

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