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

Gene ID: 2936, updated on 11-Apr-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; 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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (30678066..30727846, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (30957535..31007300, complement)
105.20220307 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

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. Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases. Vyas B, et al. Sci Rep, 2022 Mar 31. PMID 35361806, Free PMC Article
  2. Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome. Lorestani S, et al. Horm Mol Biol Clin Investig, 2021 Jun 4. PMID 34090318
  3. Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis. Zhu Z, et al. J Neurochem, 2018 Jan. PMID 29105080
  4. Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry. Ramos PS, et al. J Rheumatol, 2013 Jun. PMID 23637325, Free PMC Article
  5. Expression of glutathione reductase splice variants in human tissues. Satoh N, et al. Biochem Genet, 2010 Oct. PMID 20628807

See all (112) 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
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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
  
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_2023_10

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

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