Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu,... See more...

Aliases for GSTA4 Gene

Aliases for GSTA4 Gene

  • Glutathione S-Transferase Alpha 4 2 3 5
  • Glutathione S-Transferase A4 2 3 4
  • Glutathione S-Transferase A4-4 3 4
  • GST Class-Alpha Member 4 3 4
  • EC 2.5.1.18 4 52
  • S-(Hydroxyalkyl)Glutathione Lyase A4 3
  • Glutathione S-Aralkyltransferase A4 3
  • Glutathione S-Alkyltransferase A4 3
  • Glutathione S-Aryltransferase A4 3
  • Glutathione Transferase A4-4 3
  • GSTA4-4 3
  • GTA4 3

External Ids for GSTA4 Gene

Previous GeneCards Identifiers for GSTA4 Gene

  • GC06M052844
  • GC06M052889
  • GC06M052950
  • GC06M052674
  • GC06M052842

Summaries for GSTA4 Gene

Entrez Gene Summary for GSTA4 Gene

  • Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

GeneCards Summary for GSTA4 Gene

GSTA4 (Glutathione S-Transferase Alpha 4) is a Protein Coding gene. Diseases associated with GSTA4 include Hepatocellular Carcinoma. Among its related pathways are Drug metabolism - cytochrome P450 and Glutathione metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and glutathione transferase activity. An important paralog of this gene is GSTA2.

UniProtKB/Swiss-Prot Summary for GSTA4 Gene

  • Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).

Gene Wiki entry for GSTA4 Gene

Additional gene information for GSTA4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GSTA4 Gene

Genomics for GSTA4 Gene

GeneHancer (GH) Regulatory Elements for GSTA4 Gene

Promoters and enhancers for GSTA4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J052992 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +0.5 479 4.6 FOXK2 ZBTB40 ZNF217 CTCF TCF12 MYC ZNF300 POLR2G NCOR1 FOS 4WKR_C ENSG00000202198 GSTA4 RN7SK X05490 EFHC1 MCM3 CILK1 GSTA3 RF00019-091
GH06J052918 Enhancer 1 Ensembl ENCODE 8.5 +75.9 75874 3.8 FOXK2 ZNF217 TCF12 KDM6A TCF7 CUX1 TEAD1 GATAD2B ZKSCAN8 CTBP1 piR-56186-069 GSTA4 GSTA3 LRRC1 piR-42076-033
GH06J053685 Enhancer 0.8 dbSUPER 9.9 -691.5 -691510 2.3 ZNF639 ZNF354C ZNF623 ZNF510 ZNF341 ZNF266 FOXA2 ZBTB11 ZNF426 ZBTB1 ENSG00000249379 GSTA4 KLHL31 lnc-KLHL31-5
GH06J052908 Promoter/Enhancer 0.9 EPDnew Ensembl ENCODE 8.2 +85.7 85734 3.1 RFX1 SKI ZBTB17 FOS HLF GSTA3 GSTA4 GSTA10P
GH06J052928 Enhancer 1.1 Ensembl ENCODE 7 +65.7 65679 1.8 TCF12 JUND FOS HES1 EP300 CTBP1 JUN ZKSCAN8 FOXA2 ZSCAN9 CILK1 GSTA3 GSTA4 LINC01564 piR-40154-162 piR-38423-057
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSTA4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GSTA4

Top Transcription factor binding sites by QIAGEN in the GSTA4 gene promoter:
  • Nkx2-5
  • Oct-B1
  • oct-B2
  • oct-B3
  • POU2F1
  • POU2F1a
  • POU2F2
  • POU2F2 (Oct-2.1)
  • POU2F2B
  • POU2F2C

Genomic Locations for GSTA4 Gene

Genomic Locations for GSTA4 Gene
chr6:52,977,948-52,995,380
(GRCh38/hg38)
Size:
17,433 bases
Orientation:
Minus strand
chr6:52,842,746-52,860,178
(GRCh37/hg19)
Size:
17,433 bases
Orientation:
Minus strand

Genomic View for GSTA4 Gene

Genes around GSTA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GSTA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GSTA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GSTA4 Gene

Proteins for GSTA4 Gene

  • Protein details for GSTA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15217-GSTA4_HUMAN
    Recommended name:
    Glutathione S-transferase A4
    Protein Accession:
    O15217
    Secondary Accessions:
    • B2RD15
    • Q5T7Q8
    • Q6P4G1
    • Q9BX18
    • Q9H414

    Protein attributes for GSTA4 Gene

    Size:
    222 amino acids
    Molecular mass:
    25704 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for GSTA4 Gene

    Alternative splice isoforms for GSTA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GSTA4 Gene

Selected DME Specific Peptides for GSTA4 Gene

O15217:
  • SNIPTIK
  • RYFPVFEK
  • LAAAGVEF
  • QVPMVEIDGMKL
  • FLVGNQLS

Post-translational modifications for GSTA4 Gene

  • Ubiquitination at Lys127 and Lys138
  • Modification sites at PhosphoSitePlus

Other Protein References for GSTA4 Gene

Domains & Families for GSTA4 Gene

Gene Families for GSTA4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for GSTA4 Gene

Blocks:
  • Glutathione S-transferase, N-terminal
  • Alpha-class glutathione S-transferase signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GSTA4 Gene

GenScript: Design optimal peptide antigens:
  • Glutathione S-transferase A4-4 (GSTA4_HUMAN)
  • Glutathione S-transferase (Q6P4G1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15217

UniProtKB/Swiss-Prot:

GSTA4_HUMAN :
  • Belongs to the GST superfamily. Alpha family.
Family:
  • Belongs to the GST superfamily. Alpha family.
genes like me logo Genes that share domains with GSTA4: view

Function for GSTA4 Gene

Molecular function for GSTA4 Gene

UniProtKB/Swiss-Prot Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence=. ;.
GENATLAS Biochemistry:
glutathione S-transferase,alpha 4,ubiquitously expressed

Enzyme Numbers (IUBMB) for GSTA4 Gene

Phenotypes From GWAS Catalog for GSTA4 Gene

Gene Ontology (GO) - Molecular Function for GSTA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004364 glutathione transferase activity IDA 10329152
GO:0005515 protein binding IEA,IPI 25416956
GO:0016740 transferase activity IEA --
GO:0042802 identical protein binding IPI 16189514
GO:0042803 protein homodimerization activity IPI 10329152
genes like me logo Genes that share ontologies with GSTA4: view
genes like me logo Genes that share phenotypes with GSTA4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for GSTA4

CRISPR Products

miRNA for GSTA4 Gene

miRTarBase miRNAs that target GSTA4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSTA4

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GSTA4 Gene

Localization for GSTA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GSTA4 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GSTA4 gene
Compartment Confidence
cytosol 5
plasma membrane 2
mitochondrion 2
nucleus 2
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Gene Ontology (GO) - Cellular Components for GSTA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with GSTA4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GSTA4 Gene

Pathways & Interactions for GSTA4 Gene

genes like me logo Genes that share pathways with GSTA4: view

Pathways by source for GSTA4 Gene

2 GeneGo (Thomson Reuters) pathways for GSTA4 Gene
  • 2-Naphthylamine and 2-Nitronaphtalene metabolism
  • Glutathione metabolism

Gene Ontology (GO) - Biological Process for GSTA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006749 glutathione metabolic process IDA 10329152
GO:0006805 xenobiotic metabolic process IDA 10329152
GO:1901687 glutathione derivative biosynthetic process TAS --
genes like me logo Genes that share ontologies with GSTA4: view

No data available for SIGNOR curated interactions for GSTA4 Gene

Drugs & Compounds for GSTA4 Gene

(7) Drugs for GSTA4 Gene - From: DrugBank, ApexBio, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Glutathione Approved, Investigational Nutra Target 0
Trichloroethylene Approved Pharma 5
Water Approved Pharma 0
Hydrochloric acid Experimental Pharma 0
Sulfate Experimental, Investigational Pharma 0

(40) Additional Compounds for GSTA4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
4-Hydroxynonenal
  • (e)-4-Hydroxy-2-nonenal
  • 4-Hydroxy-2,3-trans-nonenal
  • HNE
  • trans-4-Hydroxy-2-nonenal
  • 4-Hydroxy-2,3-nonenal
75899-68-2
(1R)-Glutathionyl-(2R)-hydroxy-1,2-dihydronaphthalene
(1R)-Hydroxy-(2R)-glutathionyl-1,2-dihydronaphthalene
(1S)-Hydroxy-(2S)-glutathionyl-1,2-dihydronaphthalene
(1S,2R)-Naphthalene 1,2-oxide
  • (1S,2R)-Naphthalene epoxide

(2) ApexBio Compounds for GSTA4 Gene

Compound Action Cas Number
LB42708 Selective FTase inhibitor 226929-39-1
Lonafarnib Ftase inhibitor,potent and selective 193275-84-2
genes like me logo Genes that share compounds with GSTA4: view

Drug Products

Transcripts for GSTA4 Gene

mRNA/cDNA for GSTA4 Gene

1 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSTA4

Alternative Splicing Database (ASD) splice patterns (SP) for GSTA4 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3a · 3b · 3c · 3d ^ 4a · 4b ^ 5a · 5b · 5c · 5d · 5e · 5f · 5g ^ 6a · 6b · 6c · 6d ^ 7 ^ 8a · 8b ^
SP1: - - - - - - - - - - -
SP2: - - - - - - - - - - - - - - -
SP3: - - - - - - - - - - - - -
SP4: - - - - - -
SP5: - - - - - - - - -
SP6: - - - - - - - - - - - -
SP7: - - - - - - - - - - - - - -
SP8: - - - - - - - -
SP9: - - - - - - - - - - -
SP10: - - - - - - - - - - -
SP11: - - - - - - - -
SP12: - - - - - - - - -
SP13: - - - - -
SP14: - -
SP15: - - - - - - -
SP16: - - -
SP17: - - - - - - - - - - - - -
SP18: - - -

ExUns: 9a · 9b · 9c · 9d · 9e · 9f
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

Relevant External Links for GSTA4 Gene

GeneLoc Exon Structure for
GSTA4

Expression for GSTA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GSTA4 Gene

mRNA differential expression in normal tissues according to GTEx for GSTA4 Gene

This gene is overexpressed in Adrenal Gland (x8.9).

Protein differential expression in normal tissues from HIPED for GSTA4 Gene

This gene is overexpressed in Adrenal (19.9), Fetal testis (18.5), and Fetal Brain (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GSTA4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GSTA4

SOURCE GeneReport for Unigene cluster for GSTA4 Gene:

Hs.485557

mRNA Expression by UniProt/SwissProt for GSTA4 Gene:

O15217-GSTA4_HUMAN
Tissue specificity: Expressed at a high level in brain, placenta, and skeletal muscle and much lower in lung and liver.

Evidence on tissue expression from TISSUES for GSTA4 Gene

  • Nervous system(4.9)
  • Heart(4.3)
  • Muscle(4.3)
  • Pancreas(4.3)
  • Liver(2.4)
  • Skin(2.4)
  • Adrenal gland(2.3)
genes like me logo Genes that share expression patterns with GSTA4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for GSTA4 Gene

Orthologs for GSTA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for GSTA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GSTA4 31 30
  • 99.1 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GSTA4 31 30
  • 91.14 (n)
OneToMany
-- 31
  • 86 (a)
OneToMany
cow
(Bos Taurus)
Mammalia GSTA4 31 30
  • 90.39 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GSTA4 31
  • 63 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GSTA4 31
  • 57 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Gsta3 31
  • 50 (a)
ManyToMany
chicken
(Gallus gallus)
Aves GSTA 31
  • 59 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 62 (a)
ManyToMany
zebrafish
(Danio rerio)
Actinopterygii zgc:173961 31
  • 53 (a)
ManyToMany
gstal 31
  • 53 (a)
ManyToMany
zgc:173962 31
  • 53 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea gst-41 31
  • 26 (a)
ManyToMany
gst-10 31
  • 26 (a)
ManyToMany
Y45G12C.3 31
  • 25 (a)
ManyToMany
F56A4.4 31
  • 25 (a)
ManyToMany
F56A4.3 31
  • 22 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 41 (a)
OneToMany
Species where no ortholog for GSTA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for GSTA4 Gene

ENSEMBL:
Gene Tree for GSTA4 (if available)
TreeFam:
Gene Tree for GSTA4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSTA4: view image

Paralogs for GSTA4 Gene

Paralogs for GSTA4 Gene

(5) SIMAP similar genes for GSTA4 Gene using alignment to 3 proteins:

  • GSTA4_HUMAN
  • Q5JW88_HUMAN
  • Q6P4G1_HUMAN
genes like me logo Genes that share paralogs with GSTA4: view

Variants for GSTA4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GSTA4 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
779335 Benign: not provided 52,984,544(-) A/G SYNONYMOUS_VARIANT
rs4147617 - p.Thr163Ala
rs45551133 - p.Leu100Pro

Additional dbSNP identifiers (rs#s) for GSTA4 Gene

Structural Variations from Database of Genomic Variants (DGV) for GSTA4 Gene

Variant ID Type Subtype PubMed ID
esv2759430 CNV loss 17122850

Variation tolerance for GSTA4 Gene

Residual Variation Intolerance Score: 58.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.80; 16.79% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSTA4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSTA4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GSTA4 Gene

Disorders for GSTA4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for GSTA4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hepatocellular carcinoma
  • hcc
- elite association - COSMIC cancer census association via MalaCards
Search GSTA4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GSTA4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GSTA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GSTA4 Gene

Publications for GSTA4 Gene

  1. Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. (PMID: 9480897) Board PG (The Biochemical journal 1998) 2 3 4 23 54
  2. Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer. (PMID: 20097730) Tang H … Li D (Carcinogenesis 2010) 3 23 41 54
  3. Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal. (PMID: 20085333) Balogh LM … Atkins WM (Biochemistry 2010) 3 4 23 54
  4. Molecular implications of the human glutathione transferase A-4 gene (hGSTA4) polymorphisms in neurodegenerative diseases. (PMID: 16054170) Coppedè F … Migliore L (Mutation research 2005) 3 23 41 54
  5. Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products. (PMID: 10329152) Bruns CM … Tainer JA (Journal of molecular biology 1999) 3 4 23 54

Products for GSTA4 Gene

Sources for GSTA4 Gene