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 red... See more...

Aliases for GSR Gene

Aliases for GSR Gene

  • Glutathione-Disulfide Reductase 2 3 5
  • Glutathione Reductase, Mitochondrial 3 4
  • Glutathione S-Reductase 2 3
  • EC 1.8.1.7 4 50
  • GRase 3 4
  • GR 3 4
  • Epididymis Secretory Sperm Binding Protein Li 122m 3
  • Epididymis Luminal Protein 75 3
  • Glutathione Reductase 2
  • HEL-S-122m 3
  • EC 1.8.1 50
  • HEL-75 3
  • GSRD 3
  • GLUR 4
  • GRD1 4
  • GSR 5

External Ids for GSR Gene

Previous GeneCards Identifiers for GSR Gene

  • GC08M030441
  • GC08M030989
  • GC08M030594
  • GC08M030593
  • GC08M030655
  • GC08M029081
  • GC08M030535

Summaries for GSR Gene

Entrez Gene Summary for GSR Gene

  • 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]

GeneCards Summary for GSR Gene

GSR (Glutathione-Disulfide Reductase) is a Protein Coding gene. Diseases associated with GSR include Hemolytic Anemia Due To Glutathione Reductase Deficiency and Riboflavin Deficiency. Among its related pathways are Glutathione metabolism and Viral mRNA Translation. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and flavin adenine dinucleotide binding. An important paralog of this gene is TXNRD2.

UniProtKB/Swiss-Prot Summary for GSR Gene

Gene Wiki entry for GSR Gene

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

Genomics for GSR Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GSR Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSR on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the GSR gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • GR
  • GR-alpha
  • NF-kappaB1
  • p53

Genomic Locations for GSR Gene

Latest Assembly
chr8:30,678,066-30,727,846
(GRCh38/hg38)
Size:
49,781 bases
Orientation:
Minus strand

Previous Assembly
chr8:30,535,583-30,585,363
(GRCh37/hg19 by Entrez Gene)
Size:
49,781 bases
Orientation:
Minus strand

chr8:30,535,583-30,585,443
(GRCh37/hg19 by Ensembl)
Size:
49,861 bases
Orientation:
Minus strand

Genomic View for GSR Gene

Genes around GSR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for GSR Gene

Proteins for GSR Gene

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

    Protein Symbol:
    P00390-GSHR_HUMAN
    Recommended name:
    Glutathione reductase, mitochondrial
    Protein Accession:
    P00390
    Secondary Accessions:
    • C8KIL8
    • C8KIL9
    • C8KIM0
    • D3DSV3
    • Q7Z5C9
    • Q9NP63

    Protein attributes for GSR Gene

    Size:
    522 amino acids
    Molecular mass:
    56257 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    • Homodimer; disulfide-linked.
    SequenceCaution:
    • Sequence=AAP88037.1; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • The active site is a redox-active disulfide bond.
    • [Isoform Cytoplasmic]: Produced by alternative initiation of isoform Mitochondrial.
    • [Isoform 3]: Expressed at very high levels in peripheral blood.

    Three dimensional structures from OCA and Proteopedia for GSR Gene

    Alternative splice isoforms for GSR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GSR Gene

Selected DME Specific Peptides for GSR Gene

P00390:
  • HILIATG
  • DEMLQGFAVA
  • LTPVAIAAGR
  • QGFAVAVKMG
  • ATKADFD
  • IGGGSGG
  • VDEFQNTNV
  • IGTVGLTE
  • DFDNTVAIHPT
  • AIAAGRKL
  • GGGSGGLA

Post-translational modifications for GSR Gene

  • Ubiquitination at Lys181, Lys300, and Lys456
  • Modification sites at PhosphoSitePlus

Domains & Families for GSR Gene

Gene Families for GSR Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for GSR Gene

InterPro:
Blocks:
  • Pyridine nucleotide-disulphide oxidoreductase, NAD-binding region
  • Pyridine nucleotide-disulphide oxidoreductase, class I
  • FAD-dependent pyridine nucleotide reductase signature

Suggested Antigen Peptide Sequences for GSR Gene

GenScript: Design optimal peptide antigens:
  • Glutathione reductase, mitochondrial (GSHR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P00390

UniProtKB/Swiss-Prot:

GSHR_HUMAN :
  • Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface.
  • Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Domain:
  • Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface.
Family:
  • Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
genes like me logo Genes that share domains with GSR: view

Function for GSR Gene

Molecular function for GSR Gene

UniProtKB/Swiss-Prot Function:
Maintains high levels of reduced glutathione in the cytosol.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) + NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7; Evidence={ECO:0000269|PubMed:17185460};.
GENATLAS Biochemistry:
glutathione reductase (NADPH) FAD dependent,maintaining glutathione in the reduced state

Enzyme Numbers (IUBMB) for GSR Gene

Phenotypes From GWAS Catalog for GSR Gene

Gene Ontology (GO) - Molecular Function for GSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004362 glutathione-disulfide reductase activity IEA,IBA 21873635
GO:0009055 electron transfer activity TAS 947404
GO:0016491 oxidoreductase activity IEA --
GO:0016668 oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor IEA --
genes like me logo Genes that share ontologies with GSR: view
genes like me logo Genes that share phenotypes with GSR: view

Human Phenotype Ontology for GSR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for GSR Gene

miRTarBase miRNAs that target GSR

Transcription Factor Targets for GSR Gene

Selected GeneGlobe predicted Target genes for GSR

Inhibitory RNAs for research

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

No data available for Animal Models and HOMER Transcription for GSR Gene

Localization for GSR Gene

Subcellular locations from UniProtKB/Swiss-Prot for GSR Gene

[Isoform Mitochondrial]: Mitochondrion.
[Isoform Cytoplasmic]: 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 GSR gene
Compartment Confidence
extracellular 5
mitochondrion 5
cytosol 5
plasma membrane 4
nucleus 3
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005739 mitochondrion IBA 21873635
GO:0005759 mitochondrial matrix TAS --
GO:0005829 cytosol TAS --
GO:0009897 external side of plasma membrane IEA --
genes like me logo Genes that share ontologies with GSR: view

Pathways & Interactions for GSR Gene

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

Gene Ontology (GO) - Biological Process for GSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006749 glutathione metabolic process IEA,IBA 21873635
GO:0015949 nucleobase-containing small molecule interconversion TAS --
GO:0022900 electron transport chain IEA --
GO:0034599 cellular response to oxidative stress IBA,TAS --
GO:0045454 cell redox homeostasis IBA 21873635
genes like me logo Genes that share ontologies with GSR: view

No data available for SIGNOR curated interactions for GSR Gene

Drugs & Compounds for GSR Gene

(105) Drugs for GSR Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Carmustine Approved, Investigational Pharma Target, inhibitor 231
NADH Approved Nutra Target 0
FAD Approved Pharma Target 0
Oxidized glutathione Approved, Experimental, Investigational Pharma Target, substrate 0
Glutathione Approved, Investigational Nutra Target 0

(70) Additional Compounds for GSR Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
3-Deoxy-D-glycero-D-galacto-2-nonulosonic acid
  • 3-Deoxy-D-glycero-D-galacto-2-nonulosonate
  • 2-KDN
  • 2-Keto-3-deoxy-D-glycero-D-galacto-NONONate
  • 2-Keto-3-deoxy-D-glycero-D-galacto-NONONic acid
  • 2-oxo-3-Deoxy-D-glycero-galactononulosonate
22594-61-2
Hydrogen Ion
  • H+
  • H(+)
  • Hydron
  • Hydrogen cation
  • Proton

(1) ApexBio Compounds for GSR Gene

Compound Action Cas Number
N6022 GSNOR inhibitor 1208315-24-5
genes like me logo Genes that share compounds with GSR: view

Drug products for research

Transcripts for GSR Gene

mRNA/cDNA for GSR Gene

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

Inhibitory RNAs for research

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

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

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12
SP1:
SP2:
SP3: - -

Relevant External Links for GSR Gene

GeneLoc Exon Structure for
GSR

Expression for GSR Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GSR Gene

This gene is overexpressed in Lymph node (7.1).

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



Protein tissue co-expression partners for GSR Gene

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

SOURCE GeneReport for Unigene cluster for GSR Gene:

Hs.271510

Evidence on tissue expression from TISSUES for GSR Gene

  • Liver(4.7)
  • Blood(4.6)
  • Lung(4.5)
  • Nervous system(3.3)
  • Heart(3.1)
  • Kidney(3.1)
  • Stomach(2.9)
  • Muscle(2.8)
  • Intestine(2.8)
  • Eye(2.7)
  • Skin(2.7)
  • Pancreas(2.6)
  • Spleen(2.6)
  • Adrenal gland(2.5)
  • Bone marrow(2.3)
  • Thyroid gland(2.3)
  • Lymph node(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GSR Gene

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
Regions:
General:
  • blood
  • red blood cell
genes like me logo Genes that share expression patterns with GSR: view

Primer products for research

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for GSR Gene

Orthologs for GSR Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GSR Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GSR 29 30
  • 98.98 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GSR 29 30
  • 87.69 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GSR 29 30
  • 86.83 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GSR 30
  • 84 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gsr 29
  • 82.85 (n)
Mouse
(Mus musculus)
Mammalia Gsr 29 16 30
  • 82.4 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GSR 30
  • 82 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GSR 29 30
  • 69.98 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia GSR 30
  • 73 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia gsr 29
  • 71.76 (n)
Zebrafish
(Danio rerio)
Actinopterygii gsr 29 30
  • 65.47 (n)
OneToOne
Dr.17468 29
Worm
(Caenorhabditis elegans)
Secernentea gsr-1 29 30
  • 58.24 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AGR196W 29
  • 55.36 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GLR1 29 30 32
  • 53.18 (n)
OneToMany
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E24069g 29
  • 52.99 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons GR 29
  • 50.11 (n)
Rice
(Oryza sativa)
Liliopsida Os03g0163300 29
  • 48.87 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 62 (a)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU03339 29
  • 56.85 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes pgr1 29
  • 54.96 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.12083 29
Species where no ortholog for GSR was found in the sources mined by GeneCards:
  • 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)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • 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)
  • 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)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for GSR Gene

ENSEMBL:
Gene Tree for GSR (if available)
TreeFam:
Gene Tree for GSR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSR: view image
Alliance of Genome Resources:
Additional Orthologs for GSR

Paralogs for GSR Gene

Paralogs for GSR Gene

(5) SIMAP similar genes for GSR Gene using alignment to 4 proteins:

  • GSHR_HUMAN
  • E5RI06_HUMAN
  • H0YBD4_HUMAN
  • H0YC68_HUMAN
genes like me logo Genes that share paralogs with GSR: view

Variants for GSR Gene

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

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
993762 Benign: Hemolytic anemia due to glutathione reductase deficiency 30,709,905(-) G/GT
NM_000637.5(GSR):c.334-4dup
INTRON
993852 Uncertain Significance: Hemolytic anemia due to glutathione reductase deficiency 30,703,221(-) C/A
NM_000637.5(GSR):c.512G>T (p.Arg171Leu)
MISSENSE
993877 Uncertain Significance: Hemolytic anemia due to glutathione reductase deficiency 30,696,477(-) C/T
NM_000637.5(GSR):c.698G>A (p.Arg233His)
MISSENSE
994024 Uncertain Significance: Hemolytic anemia due to glutathione reductase deficiency 30,680,989(-) G/A
NM_000637.5(GSR):c.1334C>T (p.Thr445Met)
MISSENSE
rs1345036090 Pathogenic: Hemolytic anemia due to glutathione reductase deficiency 30,689,209(-) C/T
NM_000637.5(GSR):c.993G>A (p.Trp331Ter)
NONSENSE,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GSR Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
esv2657353 CNV deletion 23128226
esv2671289 CNV deletion 23128226
esv3616792 CNV loss 21293372
nsv473830 CNV novel sequence insertion 20440878
nsv478854 CNV novel sequence insertion 20440878
nsv516544 CNV loss 19592680
nsv824585 CNV gain 20364138

Variation tolerance for GSR Gene

Residual Variation Intolerance Score: 69.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.81; 66.94% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSR Gene

Human Gene Mutation Database (HGMD)
GSR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSR
Leiden Open Variation Database (LOVD)
GSR

SNP Genotyping and Copy Number Assays for research

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

Disorders for GSR Gene

MalaCards: The human disease database

(53) MalaCards diseases for GSR Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
hemolytic anemia due to glutathione reductase deficiency
  • hagrd
riboflavin deficiency
  • rbfvd
hemolytic anemia
  • anemia hemolytic
senile cataract
testicular torsion
  • torsion of testicular cord
- elite association - COSMIC cancer census association via MalaCards
Search GSR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GSHR_HUMAN
  • Hemolytic anemia due to glutathione reductase deficiency (HAGRD) [MIM:618660]: An autosomal recessive disease characterized by hemolytic anemia and impaired activity of glutathione reductase. Patients experience hemolytic anemia in response to oxidative stress or ingestion of fava beans. {ECO:0000269 PubMed:17185460}. Note=The disease is caused by variants affecting the gene represented in this entry.

Genatlas disease for GSR Gene

hemolytic crisis

Additional Disease Information for GSR

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with GSR: view

Publications for GSR Gene

  1. Molecular basis of glutathione reductase deficiency in human blood cells. (PMID: 17185460) Kamerbeek NM … Roos D (Blood 2007) 3 4 22 72
  2. Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers. (PMID: 9546215) Becker K … Karplus PA (Nature structural biology 1998) 3 4 22
  3. Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity. (PMID: 9174360) Stoll VS … Pai EF (Biochemistry 1997) 3 4 22
  4. Kinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor. (PMID: 8626496) Savvides SN … Karplus PA (The Journal of biological chemistry 1996) 3 4 22
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 40

Products for GSR Gene

Sources for GSR Gene