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    GSR glutathione-disulfide reductase [ Homo sapiens (human) ]

    Gene ID: 2936, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GSRprovided by HGNC
    Official Full Name
    glutathione-disulfide reductaseprovided by HGNC
    Primary source
    HGNC:HGNC:4623
    See related
    Ensembl:ENSG00000104687 MIM:138300; AllianceGenome:HGNC:4623
    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
    GR; GSRD; HEL-75; CNSHA10; HEL-S-122m
    Summary
    This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]
    Expression
    Ubiquitous expression in colon (RPKM 26.7), kidney (RPKM 25.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GSR in Genome Data Viewer
    Location:
    8p12
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (30678066..30727846, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (30957535..31007300, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (30535583..30585363, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene RNA binding protein, mRNA processing factor Neighboring gene uncharacterized LOC124901929 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30396862-30397470 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30396143-30396854 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30397471-30398079 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30398080-30398688 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr8:30398689-30399296 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr8:30399297-30399906 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30400515-30401122 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30401123-30401730 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27212 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30406725-30407384 Neighboring gene Sharpr-MPRA regulatory region 2547 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19077 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:30415639-30416140 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:30416141-30416640 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30422314-30422922 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19078 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19079 Neighboring gene general transcription factor IIE subunit 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27213 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:30514282-30514953 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19080 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30515625-30516296 Neighboring gene RNA, U5A small nuclear 3, pseudogene Neighboring gene small integral membrane protein 18 Neighboring gene NANOG hESC enhancer GRCh37_chr8:30560335-30560881 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19082 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30584261-30584948 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19083 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19084 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:30586711-30587235 Neighboring gene uncharacterized LOC105379356 Neighboring gene uncharacterized LOC105379355 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27214 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:30601364-30602332 Neighboring gene UBX domain protein 8 Neighboring gene HIKESHI pseudogene 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury. Zhu H, et al. Mol Cell Biochem, 2007 Jul. PMID 17206382
    2. Involvement of glutathione and glutathione-related enzymes in the protection of normal and trisomic human fibroblasts against daunorubicin. Zatorska A, et al. Cell Biol Int, 2002. PMID 12095224
    3. The decrease in antioxidant potential in human brain tumours. Dudek H, et al. Rocz Akad Med Bialymst, 2002. PMID 12533953
    4. Antioxidant potential in esophageal, stomach and colorectal cancers. Skrzydlewska E, et al. Hepatogastroenterology, 2003 Jan-Feb. PMID 12630007
    5. Study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants. De Vega L, et al. Transplant Proc, 2003 Jun. PMID 12826156

    See all (121) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases.
      Title: Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases.
    2. Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome.
      Title: Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome.
    3. MicroRNA-362-5p promotes the proliferation and inhibits apoptosis of trophoblast cells via targeting glutathione-disulfide reductase.
      Title: MicroRNA-362-5p promotes the proliferation and inhibits apoptosis of trophoblast cells via targeting glutathione-disulfide reductase.
    4. AMPKalpha1 is overexpressed in colorectal cancer (CRC) patient specimens and the high expression is correlated with poor survival. AMPKalpha1 maintains high level of reduced glutathione to keep redox homeostasis under stress conditions, thus promoting CRC cell survival. Mechanistically, AMPKalpha1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity.
      Title: AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.
    5. It has been shown that acute aerobic exercise activates Nrf2 in young men, irrespective of training intensity, but that high-intensity exercise demonstrated a greater effect on increasing glutathione reductase activity which could indicate improved redox potential.
      Title: Effect of exercise intensity on Nrf2 signalling in young men.
    6. GSR expression was higher in TMZ-resistant cells than in sensitive cells. GSR silencing in drug-resistant cells improved the sensitivity of cells to TMZ or cisplatin. Over-expression resulted in resistance. GSR partially prevented the oxidative stress caused by L-buthionine -sulfoximine. The action of GSR in drug resistance is associated with the modulation of redox homeostasis. High GSR correlated with lower survival.
      Title: Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis.
    7. Plasma glutathione reductase (GR) activity was correlated with erythrocyte GR activity and the erythrocyte reduced glutathione/glutathione disulfide ratio. A decrease in plasma GR activity was associated with an increase in mortality in septic shock.
      Title: Plasma glutathione reductase activity and prognosis of septic shock.
    8. Glutathione reductase reduces mitochondrial protein mitoNEET [2Fe-2S] clusters.
      Title: Reduction of mitochondrial protein mitoNEET [2Fe-2S] clusters by human glutathione reductase.
    9. The recurrence of benign tumors of mammary gland occurred predominantly in women-carriers of mutant alleles with polymorphism rs8190924 of gene GSR and AA rs3763511of gene DKK4.
      Title: [MODERN METHODS OF PROGNOSTICATION OF THE RECURRENCES OCCURRENCE AFTER SURGICAL TREATMENT OF THE MAMMARY GLAND BENIGN TUMORS].
    10. GSR was the most significant single SNP association with systemic lupus erythematosus in African Americans.
      Title: Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry.
    Submit: New GeneRIF Correction See all GeneRIFs (34)

    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
    Hemolytic anemia due to glutathione reductase deficiency
    MedGen: C5231513 OMIM: 618660 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human glutathione reductase, mitochondria (GSR) at amino acid residues 67-68 by the HIV-1 protease PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • MGC78522

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NADP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables electron transfer activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables flavin adenine dinucleotide binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutathione-disulfide reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell redox homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to oxidative stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutathione metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    glutathione reductase, mitochondrial
    Names
    GRase
    epididymis luminal protein 75
    epididymis secretory sperm binding protein Li 122m
    glutathione S-reductase
    NP_000628.2
    NP_001182031.1
    NP_001182032.1
    NP_001182033.1
    XP_047277683.1
    XP_047277684.1
    XP_054216345.1

    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.

    Genomic

    1. NG_027719.1 RefSeqGene

      Range
      5124..54904
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1167

    mRNA and Protein(s)

    1. NM_000637.5 → NP_000628.2  glutathione reductase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000628.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC103959, BC069244, CA944703
      Consensus CDS
      CCDS34877.1
      UniProtKB/Swiss-Prot
      C8KIL8, C8KIL9, C8KIM0, D3DSV3, P00390, Q7Z5C9, Q9NP63
      UniProtKB/TrEMBL
      V9HW90
      Related
      ENSP00000221130.5, ENST00000221130.11
      Conserved Domains (3) summary
      TIGR01421
      Location:63 → 522
      gluta_reduc_1; glutathione-disulfide reductase, animal/bacterial
      pfam00070
      Location:233 → 307
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:412 → 520
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

    2. NM_001195102.3 → NP_001182031.1  glutathione reductase, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_001182031.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as delta8) lacks an in-frame coding exon, as compared to variant 1. The resulting isoform (2) lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AB519179, AC103959, BM148117, CA944703
      Consensus CDS
      CCDS56531.1
      UniProtKB/Swiss-Prot
      P00390
      Related
      ENSP00000445516.1, ENST00000546342.5
      Conserved Domains (3) summary
      TIGR01421
      Location:63 → 493
      gluta_reduc_1; glutathione-disulfide reductase, animal/bacterial
      pfam00070
      Location:233 → 282
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:383 → 491
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

    3. NM_001195103.3 → NP_001182032.1  glutathione reductase, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001182032.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3, also known as delta9) lacks an in-frame coding exon, as compared to variant 1. The resulting isoform (3) lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AB519180, AC103959, BM148117, CA944703
      Consensus CDS
      CCDS56532.1
      UniProtKB/Swiss-Prot
      P00390
      Related
      ENSP00000444559.1, ENST00000541648.5
      Conserved Domains (3) summary
      TIGR01421
      Location:63 → 469
      gluta_reduc_1; glutathione-disulfide reductase, animal/bacterial
      pfam00070
      Location:233 → 302
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:359 → 467
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

    4. NM_001195104.3 → NP_001182033.1  glutathione reductase, mitochondrial isoform 4

      See identical proteins and their annotated locations for NP_001182033.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as delta8+9) lacks two consecutive coding exons, as compared to variant 1. The reading frame is not affected and the resulting isoform (4) lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AB519181, AC103959, BM148117, CA944703
      Consensus CDS
      CCDS56530.1
      UniProtKB/Swiss-Prot
      P00390
      Related
      ENSP00000438845.1, ENST00000537535.5
      Conserved Domains (3) summary
      TIGR01421
      Location:63 → 440
      gluta_reduc_1; glutathione-disulfide reductase, animal/bacterial
      pfam00070
      Location:233 → 286
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:330 → 438
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      30678066..30727846 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047421727.1 → XP_047277683.1  glutathione reductase, mitochondrial isoform X1

    2. XM_047421728.1 → XP_047277684.1  glutathione reductase, mitochondrial isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      30957535..31007300 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360370.1 → XP_054216345.1  glutathione reductase, mitochondrial isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P00390.2 GenPept UniProtKB/Swiss-Prot:P00390

    Gene LinkOut

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

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