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

Gene ID: 197322, updated on 5-Mar-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
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Genomic context

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Location:
16q24.3
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (89093852..89156233)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (95173811..95236254)
105.20220307 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
  • 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. 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
  2. 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
  3. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Bowman CE, et al. Adv Biol Regul, 2019 Jan. PMID 30201289, Free PMC Article
  4. 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
  5. Analysis of differentially expressed genes and microRNAs in alcoholic liver disease. Liu Y, et al. Int J Mol Med, 2013 Mar. PMID 23337955

See all (39) 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
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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

  • 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 IDA
Inferred from Direct Assay
more info
 PubMed 
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
  
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_2023_10

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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