Details for: ACSM5

Gene ID: 54988

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ACSM5

Ensembl ID: ENSG00000183549

Description: acyl-CoA synthetase medium chain family member 5

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • midzonal region hepatocyte CL0019028
    CSI 6.31
    rCSI 14.82%
    PRS 96.83
  • centrilobular region hepatocyte CL0019029
    CSI 5.27
    rCSI 13.76%
    PRS 96.34
  • Kupffer cell CL0000091
    CSI 4.05
    rCSI 9.26%
    PRS 98.7
  • hepatocyte CL0000182
    CSI 3.63
    rCSI 6.5%
    PRS 97.28
  • adipocyte CL0000136
    CSI 3.25
    rCSI 4.17%
    PRS 96.07
  • myofibroblast cell CL0000186
    CSI 2.89
    rCSI 4.01%
    PRS 97.73
  • periportal region hepatocyte CL0019026
    CSI 2.43
    rCSI 9.43%
    PRS 96.66

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ACSM5](/details-gene/54988) (Acyl-CoA Synthetase Medium Chain Family Member 5) is a protein-coding gene located on chromosome 16p12.3. It encodes a mitochondrial enzyme that functions as a medium-chain fatty acid-CoA ligase. This enzyme plays a crucial role in cellular metabolism, particularly in the activation of medium-chain fatty acids for subsequent beta-oxidation. Its function extends to xenobiotic metabolism, where it participates in the conjugation and detoxification of carboxylic acids such as benzoic acid and salicylate [Link](https://doi.org/10.1080/17425255.2016.1206888). Expression data indicates that [ACSM5](/details-gene/54988) is a highly significant gene in liver-associated cells, with its highest expression and specificity observed in various subtypes of [hepatocytes](/details-cell/CL0000182), suggesting a central role in hepatic lipid handling and drug metabolism. ## Cellular Roles and Expression Landscape The expression profile of [ACSM5](/details-gene/54988) highlights its specialized function within metabolically active tissues, primarily the liver. **Overall**, the gene shows the highest significance in [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 6.31) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 5.27), indicating a potential role in the specific metabolic functions associated with these liver zones. Its high significance is also noted in general [hepatocytes](/details-cell/CL0000182), resident liver macrophages known as [Kupffer cells](/details-cell/CL0000091), and [adipocytes](/details-cell/CL0000136). This expression pattern is consistent with its enzymatic function in fatty acid metabolism, a key process in both liver cells and fat cells. The presence in [Kupffer cells](/details-cell/CL0000091) may suggest a role in processing lipid antigens or in the metabolic reprogramming of these immune cells within the liver microenvironment. The significant, albeit lower, expression in [myofibroblast cells](/details-cell/CL0000186) could imply a role in cellular energetics during tissue remodeling or fibrosis. The collective data firmly establishes [ACSM5](/details-gene/54988) as a key metabolic enzyme whose activity is concentrated in cells central to lipid homeostasis and detoxification. ## Pathways and Molecular Function Functionally, [ACSM5](/details-gene/54988) is annotated as a ligase with [medium-chain fatty acid-coa ligase activity](/details-cell/GO:0031956) and [fatty acid ligase activity](/details-cell/GO:0015645), requiring ATP binding ([GO:0005524](/details-cell/GO:0005524)) for its catalytic function. These activities place it squarely within the biological process of the [acyl-coa metabolic process](/details-cell/GO:0006637). As a mitochondrial matrix ([GO:0005759](/details-cell/GO:0005759)) protein, it prepares medium-chain fatty acids for entry into the mitochondrial beta-oxidation pathway. Beyond endogenous lipid metabolism, Reactome pathway analysis reveals a critical role for [ACSM5](/details-gene/54988) in xenobiotic metabolism. It is a component of the [Phase II - conjugation of compounds](/details-cell/R-HSA-156580) pathway, specifically involved in the [conjugation of carboxylic acids](/details-cell/R-HSA-159424). This is exemplified by its participation in the metabolic pathways for [aspirin adme](/details-cell/R-HSA-9749641) and the [conjugation of salicylate with glycine](/details-cell/R-HSA-177128). This dual role in both energy metabolism and drug detoxification is consistent with its high expression in [hepatocytes](/details-cell/CL0000182), the primary site for these processes in the body. Research suggests that this gene family may be linked to multiple metabolic risk factors [Link](https://doi.org/10.1161/01.hyp.0000064944.60569.87). ## Research Directions The dual involvement of [ACSM5](/details-gene/54988) in both fatty acid metabolism and drug detoxification presents several compelling avenues for future research, particularly concerning metabolic disease and pharmacogenomics. **Proposed Hypotheses:** 1. **Given its role in detoxifying aspirin and other salicylates, reduced expression or functional variants of [ACSM5](/details-gene/54988) in [hepatocytes](/details-cell/CL0000182) may increase an individual's susceptibility to drug-induced liver injury (DILI) from common nonsteroidal anti-inflammatory drugs (NSAIDs).** This could occur through the accumulation of toxic intermediates or the shunting of the drug into alternative, more harmful metabolic pathways. 2. **Dysregulation of [ACSM5](/details-gene/54988) activity in [hepatocytes](/details-cell/CL0000182) and [adipocytes](/details-cell/CL0000136) contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD).** Impaired ability to activate and metabolize medium-chain fatty acids could lead to their accumulation as triglycerides within the liver, promoting steatosis and subsequent inflammation. **Experimental Approach:** To test the first hypothesis regarding DILI, an in vitro study could be conducted using primary human [hepatocytes](/details-cell/CL0000182) or iPSC-derived liver organoids. [ACSM5](/details-gene/54988) expression would be knocked down using CRISPR interference (CRISPRi). Control and knockdown cells would then be exposed to physiologically relevant concentrations of salicylic acid. Endpoints would include assays for cell viability (e.g., LDH release), oxidative stress (e.g., ROS production), and a detailed metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS) to quantify the accumulation of salicylic acid and its various conjugates. This would directly test whether [ACSM5](/details-gene/54988) is necessary for the safe detoxification of this class of drugs in human liver cells. **Therapeutic Potential:** [ACSM5](/details-gene/54988) is unlikely to be a suitable target for systemic inhibition due to its fundamental role in fatty acid metabolism, which could lead to significant toxicity. However, its function presents opportunities in personalized medicine and as a target for activation. Genotyping for low-activity variants of [ACSM5](/details-gene/54988) could potentially be used as a pharmacogenomic marker to identify patients at higher risk for DILI from certain drugs. Conversely, developing small-molecule activators of [ACSM5](/details-gene/54988) could represent a novel therapeutic strategy for metabolic disorders like NAFLD, aiming to enhance the liver's capacity to process and clear excess fatty acids.

Genular Protein ID: 1237004186

Symbol: ACSM5_HUMAN

Name: Acyl-coenzyme A synthetase ACSM5, mitochondrial

UniProtKB Accession Codes:

Q6NUN0 Q96AV1 Q96CX8 Q9NWV3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 13 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 3 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 27351777

Title: Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.

PubMed ID: 27351777

DOI: 10.1080/17425255.2016.1206888

PubMed ID: 12654705

Title: An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to multiple risk factors.

PubMed ID: 12654705

DOI: 10.1161/01.hyp.0000064944.60569.87

Sequence Information:

  • Length: 579
  • Mass: 64760
  • Checksum: 9493CB853CE29CB1
  • Sequence:
    • MRPWLRHLVL QALRNSRAFC GSHGKPAPLP VPQKIVATWE AISLGRQLVP EYFNFAHDVL 
DVWSRLEEAG HRPPNPAFWW VNGTGAEIKW SFEELGKQSR KAANVLGGAC GLQPGDRMML 
VLPRLPEWWL VSVACMRTGT VMIPGVTQLT EKDLKYRLQA SRAKSIITSD SLAPRVDAIS 
AECPSLQTKL LVSDSSRPGW LNFRELLREA STEHNCMRTK SRDPLAIYFT SGTTGAPKMV 
EHSQSSYGLG FVASGRRWVA LTESDIFWNT TDTGWVKAAW TLFSAWPNGS CIFVHELPRV 
DAKVILNTLS KFPITTLCCV PTIFRLLVQE DLTRYQFQSL RHCLTGGEAL NPDVREKWKH 
QTGVELYEGY GQSETVVICA NPKGMKIKSG SMGKASPPYD VQIVDDEGNV LPPGEEGNVA 
VRIRPTRPFC FFNCYLDNPE KTAASEQGDF YITGDRARMD KDGYFWFMGR NDDVINSSSY 
RIGPVEVESA LAEHPAVLES AVVSSPDPIR GEVVKAFIVL TPAYSSHDPE ALTRELQEHV 
KRVTAPYKYP RKVAFVSELP KTVSGKIQRS KLRSQEWGK