Details for: GLYATL1

Gene ID: 92292

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: GLYATL1

Ensembl ID: ENSG00000166840

Description: glycine-N-acyltransferase like 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 5.3
    rCSI 12.45%
    PRS 96.07
  • hepatocyte CL0000182
    CSI 3.54
    rCSI 6.33%
    PRS 96.78
  • periportal region hepatocyte CL0019026
    CSI 3.31
    rCSI 12.88%
    PRS 95.79
  • epithelial cell of proximal tubule CL0002306
    CSI 3.19
    rCSI 7.79%
    PRS 95.11
  • intrahepatic cholangiocyte CL0002538
    CSI 2.98
    rCSI 7.14%
    PRS 97.77
  • kidney epithelial cell CL0002518
    CSI 2.42
    rCSI 4.62%
    PRS 99.51
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 2.37
    rCSI 18.82%
    PRS 95.85
  • centrilobular region hepatocyte CL0019029
    CSI 2.18
    rCSI 5.69%
    PRS 95.54

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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  • 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 [GLYATL1](/details-gene/92292) (glycine-N-acyltransferase like 1) is a protein-coding gene located on chromosome 11q12.1. It encodes a mitochondrial enzyme with glycine N-acyltransferase and glutamine N-acyltransferase activity. Functionally, [GLYATL1](/details-gene/92292) is involved in Phase II conjugation, a critical detoxification process that renders xenobiotics and endogenous metabolites more water-soluble for excretion. This role is consistent with its highly specific and abundant expression profile, which is dominated by cell types central to metabolic and detoxification functions, particularly [hepatocytes](/details-cell/CL0000182) in the liver and [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney. Research suggests its expression is suppressed in hepatocellular carcinoma, pointing towards a potential role as a tumor suppressor [[Link](https://doi.org/10.1016/j.bbrc.2012.03.099)]. ## Cellular Roles and Expression Landscape The expression pattern of [GLYATL1](/details-gene/92292) strongly indicates a specialized function in metabolic and excretory organs. **Overall**, the gene shows the highest significance in liver and kidney cells. The most prominent expression is observed in various subtypes of liver parenchymal cells, including [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 5.30), [hepatocytes](/details-cell/CL0000182) (CSI: 3.54), [periportal region hepatocytes](/details-cell/CL0019026) (CSI: 3.31), and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 2.18). This robust expression across different functional zones of the liver lobule underscores its integral role in hepatic metabolism. High significance is also noted in [intrahepatic cholangiocytes](/details-cell/CL0002538) (CSI: 2.98), the epithelial cells lining the bile duct. Beyond the liver, [GLYATL1](/details-gene/92292) is a key marker for [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney (CSI: 3.19), a cell type responsible for reabsorption and secretion processes. This dual-organ prominence in both the liver and kidney solidifies its role as a key enzyme in the body's primary systems for processing and eliminating foreign compounds and metabolic waste. ## Pathways and Molecular Function The molecular function of [GLYATL1](/details-gene/92292) is well-defined by its Gene Ontology annotations and its involvement in specific metabolic pathways. It is localized to the [mitochondrion](/details-cell/GO:0005739) and possesses both [glutamine n-acyltransferase activity](/details-cell/GO:0047946) and [glycine n-acyltransferase activity](/details-cell/GO:0047961). These enzymatic activities are central to the [glutamine metabolic process](/details-cell/GO:0006541). Reactome pathway analysis further clarifies its physiological role. [GLYATL1](/details-gene/92292) is a component of overarching metabolic pathways such as [Metabolism](/details-pathway/R-HSA-1430728) and [Biological oxidations](/details-pathway/R-HSA-211859). More specifically, it is a key player in [Phase II - conjugation of compounds](/details-pathway/R-HSA-156580), which involves the [conjugation of carboxylic acids](/details-pathway/R-HSA-159424) with amino acids. This is exemplified by its role in processes like the [conjugation of benzoate with glycine](/details-pathway/R-HSA-177135). Notably, these functions are directly relevant to pharmacokinetics, as highlighted by its inclusion in pathways for [Drug ADME](/details-pathway/R-HSA-9748784) (Absorption, Distribution, Metabolism, and Excretion). Specific examples include the metabolism of common drugs like aspirin ([Aspirin ADME](/details-pathway/R-HSA-9749641)) and salicylates ([conjugation of salicylate with glycine](/details-pathway/R-HSA-177128)). This pathway involvement is highly consistent with its strong expression in [hepatocytes](/details-cell/CL0000182) and [kidney epithelial cells](/details-cell/CL0002518), the primary sites of drug metabolism and clearance. ## Research Directions The well-defined role of [GLYATL1](/details-gene/92292) in detoxification and its specific expression pattern provide a strong foundation for further investigation, particularly concerning its role in disease and pharmacogenomics. **Proposed Hypotheses:** 1. Based on evidence that its activity is depressed in hepatocellular carcinoma [[Link](https://doi.org/10.1016/j.bbrc.2012.03.099)], we hypothesize that the epigenetic silencing or mutational inactivation of [GLYATL1](/details-gene/92292) is a pro-tumorigenic event. Loss of its function may lead to the accumulation of toxic endogenous metabolites or xenobiotics in [hepatocytes](/details-cell/CL0000182), promoting DNA damage and neoplastic transformation. 2. Given its role in metabolizing salicylates and other carboxylic acid-containing drugs, it is hypothesized that functional polymorphisms in the [GLYATL1](/details-gene/92292) gene contribute significantly to inter-individual differences in drug response and adverse event profiles. Individuals with low-activity variants may be at higher risk for toxicity from standard doses of drugs metabolized through glycine conjugation. **Experimental Approach:** To test the hypothesis that [GLYATL1](/details-gene/92292) acts as a tumor suppressor in the liver, a multi-pronged approach could be employed. First, CRISPR-Cas9 could be used to knock out [GLYATL1](/details-gene/92292) in a non-transformed human hepatocyte cell line (e.g., HepaRG). These knockout cells and isogenic controls could then be subjected to long-term culture or exposed to low-dose chemical carcinogens. Endpoints would include assays for transformation (e.g., soft agar growth), DNA damage (e.g., comet assay), and comprehensive metabolic profiling via mass spectrometry to identify accumulating toxic substrates. In parallel, analysis of large-scale cancer genomics datasets (e.g., TCGA) could be performed to correlate [GLYATL1](/details-gene/92292) expression levels and mutation status with patient survival and tumor grade in hepatocellular carcinoma. **Therapeutic Potential:** The existing evidence suggests [GLYATL1](/details-gene/92292) functions as a tumor suppressor. Therefore, it is not a candidate for inhibition. Instead, therapeutic strategies would focus on **activation or restoration** of its function in cancer cells. This could potentially be achieved through the development of small molecule activators that enhance its enzymatic activity or through gene therapy approaches aimed at re-introducing a functional copy of the gene into tumor cells. Given its high tissue specificity, a therapy designed to augment [GLYATL1](/details-gene/92292) function might offer a targeted effect on the liver with a reduced risk of off-target effects in other tissues.

Genular Protein ID: 680524102

Symbol: GLYL1_HUMAN

Name: Acyl-CoA:glycine N-acyltransferase-like protein 1

UniProtKB Accession Codes:

Q969I3 A6NDT0 Q7Z510 Q8NAW8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 6 Ensembl 4 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 3 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SwissPalm 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: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

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: 22475485

Title: Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma.

PubMed ID: 22475485

DOI: 10.1016/j.bbrc.2012.03.099

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

Sequence Information:

  • Length: 302
  • Mass: 35101
  • Checksum: D6E7513A9B8769B0
  • Sequence:
    • MILLNNSHKL LALYKSLARS IPESLKVYGS VYHINHGNPF NMEVLVDSWP EYQMVIIRPQ 
KQEMTDDMDS YTNVYRMFSK EPQKSEEVLK NCEIVNWKQR LQIQGLQESL GEGIRVATFS 
KSVKVEHSRA LLLVTEDILK LNASSKSKLG SWAETGHPDD EFESETPNFK YAQLDVSYSG 
LVNDNWKRGK NERSLHYIKR CIEDLPAACM LGPEGVPVSW VTMDPSCEVG MAYSMEKYRR 
TGNMARVMVR YMKYLRQKNI PFYISVLEEN EDSRRFVGQF GFFEASCEWH QWTCYPQNLV 
PF

Genular Protein ID: 1944641698

Symbol: A0A8I5KVG3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A8I5KVG3

Database IDs:

ARBA 3 CTD 1 DisGeNET 1 EMBL 6 Ensembl 2 GO 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 4 NCBI Taxonomy 1 PANTHER 2 PeptideAtlas 2 Pfam 4 Proteomes 2 ProteomicsDB 1 RefSeq 6 RuleBase 1 SMR 1 SUPFAM 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

Sequence Information:

  • Length: 325
  • Mass: 37687
  • Checksum: 5256976F0A14F90B
  • Sequence:
    • MVSQEGSEVE LLVSPGARSE HGRYLQDPIV SIDLSEWLRI IEFLLQGLKV YGSVYHINHG 
NPFNMEVLVD SWPEYQMVII RPQKQEMTDD MDSYTNVYRM FSKEPQKSEE VLKNCEIVNW 
KQRLQIQGLQ ESLGEGIRVA TFSKSVKVEH SRALLLVTED ILKLNASSKS KLGSWAETGH 
PDDEFESETP NFKYAQLDVS YSGLVNDNWK RGKNERSLHY IKRCIEDLPA ACMLGPEGVP 
VSWVTMDPSC EVGMAYSMEK YRRTGNMARV MVRYMKYLRQ KNIPFYISVL EENEDSRRFV 
GQFGFFEASC EWHQWTCYPQ NLVPF