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    GSTM4 glutathione S-transferase mu 4 [ Homo sapiens (human) ]

    Gene ID: 2948, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GSTM4provided by HGNC
    Official Full Name
    glutathione S-transferase mu 4provided by HGNC
    Primary source
    HGNC:HGNC:4636
    See related
    Ensembl:ENSG00000168765 MIM:138333; AllianceGenome:HGNC:4636
    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
    GTM4; GSTM4-4
    Summary
    Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in duodenum (RPKM 44.6), small intestine (RPKM 30.1) and 23 other tissues See more
    Orthologs
    all
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    Genomic context

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    See GSTM4 in Genome Data Viewer
    Location:
    1p13.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (109656099..109667727)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (109684537..109696166)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (110198721..110208119)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:110162157-110162685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110163216-110163744 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110164805-110165334 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110166705-110167518 Neighboring gene adenosine monophosphate deaminase 2 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:110170748-110171947 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110171947-110172506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110173069-110173628 Neighboring gene Sharpr-MPRA regulatory region 1493 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110186678-110187551 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1449 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110199362-110199947 Neighboring gene ribosomal protein L7 pseudogene 8 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1157 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1450 Neighboring gene glutathione S-transferase mu 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1451 Neighboring gene glutathione S-transferase mu 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. Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4. Comstock KE, et al. J Biol Chem, 1993 Aug 15. PMID 8349586
    2. Screening for inter-individual splicing differences in human GSTM4 and the discovery of a single nucleotide substitution related to the tandem skipping of two exons. Denson J, et al. Gene, 2006 Sep 1. PMID 16854533
    3. A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer. Liloglou T, et al. Lung Cancer, 2002 Aug. PMID 12140136
    4. Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain. Beuckmann CT, et al. Neurochem Res, 2000 May. PMID 10905636
    5. Glutathione transferases of classes alpha, mu and pi show selective expression in different regions of rat kidney. Rozell B, et al. Xenobiotica, 1993 Aug. PMID 8284940

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Our data suggest that the combined treatment with chemotherapy and GST(GSTM1, GSTM4 and GSTT1 ) inhibitors such as EA might be an interesting option for patients with chemoresistant Hodgkin's lymphoma
      Title: Glutathione-S-transferases and Chemotherapy Resistance of Hodgkin's Lymphoma Cell Lines.
    2. There were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05).
      Title: The expression of GST isoenzymes and p53 in non-small cell lung cancer.
    3. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    4. We observed suggestive associations between survival and GSTT1 copy number and GSTA5, GSTM4, and ABCC4 single nucleotide polymorphisms
      Title: Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy.
    5. GSTM4 contributes to the cancerous behavior of Ewing's sarcoma.
      Title: GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance.
    6. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
      Title: Genetic variants in GSTM3 gene within GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster influence breast cancer susceptibility depending on GSTM1.
    7. GSTM4 (glutathione S-transferase mu 4) haplotype 1101000 may be an important determinant for lung function growth
      Title: Variation in the GST mu locus and tobacco smoke exposure as determinants of childhood lung function.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population.
    9. A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer.
      Title: A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer.
    10. a novel splice variant of GSTM4 that resulted from tandem skipping of exons 4 and 5 is identified.
      Title: Screening for inter-individual splicing differences in human GSTM4 and the discovery of a single nucleotide substitution related to the tandem skipping of two exons.
    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

    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

    • MGC9247, MGC131945

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables glutathione binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables glutathione transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutathione transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables leukotriene-C4 synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in glutathione metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutathione metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in long-chain fatty acid biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nitrobenzene metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in xenobiotic catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in intercellular bridge IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    glutathione S-transferase Mu 4
    Names
    GST class-mu 4
    GST-Mu2
    GTS-Mu2
    S-(hydroxyalkyl)glutathione lyase M4
    glutathione S-alkyltransferase M4
    glutathione S-aralkyltransferase M4
    glutathione S-aryltransferase M4
    glutathione S-transferase M4
    leukotriene C4 synthase GSTM4
    testis tissue sperm-binding protein Li 60n
    NP_000841.1
    NP_671489.1
    XP_016856574.1
    XP_047274608.1
    XP_047274610.1
    XP_054192141.1
    XP_054192142.1

    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.

    mRNA and Protein(s)

    1. NM_000850.5 → NP_000841.1  glutathione S-transferase Mu 4 isoform 1

      See identical proteins and their annotated locations for NP_000841.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC000031, BC108729, DA895954
      Consensus CDS
      CCDS807.1
      UniProtKB/Swiss-Prot
      A8K765, Q03013, Q05465, Q32NC1, Q4JNT8, Q6FH87
      UniProtKB/TrEMBL
      A0A140VKE3
      Related
      ENSP00000358851.4, ENST00000369836.9
      Conserved Domains (3) summary
      cd03209
      Location:92 → 211
      GST_C_Mu; C-terminal, alpha helical domain of Class Mu Glutathione S-transferases
      COG0625
      Location:3 → 189
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]
      cd03075
      Location:3 → 84
      GST_N_Mu; GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, ...

    2. NM_147148.3 → NP_671489.1  glutathione S-transferase Mu 4 isoform 2

      See identical proteins and their annotated locations for NP_671489.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame exon in the 3' coding region and 3' UTR, compared to variant 1. It encodes a protein which has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC000031, BI791533, DA895954, M99422
      Consensus CDS
      CCDS806.1
      UniProtKB/Swiss-Prot
      Q03013
      Related
      ENSP00000316471.5, ENST00000326729.9
      Conserved Domains (3) summary
      cd03209
      Location:92 → 189
      GST_C_Mu; C-terminal, alpha helical domain of Class Mu Glutathione S-transferases
      COG0625
      Location:3 → 189
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]
      cd03075
      Location:3 → 84
      GST_N_Mu; GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, ...

    RNA

    1. NR_024538.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate exon in the 5' coding region resulting in a frameshift and early stop codon, compared to variant 1. The predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated decay (NMD).
      Source sequence(s)
      AC000031, BC015513, DA895954, M99421
      Related
      ENST00000495742.5

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      109656099..109667727
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017001085.2 → XP_016856574.1  glutathione S-transferase Mu 4 isoform X1

    2. XM_047418654.1 → XP_047274610.1  glutathione S-transferase Mu 4 isoform X3

    3. XM_047418652.1 → XP_047274608.1  glutathione S-transferase Mu 4 isoform X2

      UniProtKB/TrEMBL
      A6NNT0
      Related
      ENSP00000358848.1, ENST00000369833.5

    RNA

    1. XR_007059238.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      109684537..109696166
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054336166.1 → XP_054192141.1  glutathione S-transferase Mu 4 isoform X4

    2. XM_054336167.1 → XP_054192142.1  glutathione S-transferase Mu 4 isoform X5

    RNA

    1. XR_008486012.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_147149.1: Suppressed sequence

      Description
      NM_147149.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q03013.3 GenPept UniProtKB/Swiss-Prot:Q03013

    Gene LinkOut

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

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