{"entity":{"id":"gsr","kind":"target","name":"Glutathione reductase","aka":[],"tldr":"Glutathione reductase regenerates the cell's main antioxidant; the nitrosourea carmustine inhibits it as a side action to its DNA cross-linking, which adds to the drug's toxicity as well as its effect.","summary":"Glutathione reductase converts oxidised glutathione back to its reduced form, maintaining the cell's largest pool of antioxidant. Carmustine (BCNU), the nitrosourea used in glioma and in high-dose conditioning for lymphoma, carbamoylates the enzyme and inactivates it, so cells treated with the drug face oxidative stress as well as DNA cross-links; the effect is thought to contribute to carmustine's lung toxicity. Because tumours with high glutathione levels resist alkylating agents and platinum drugs, the glutathione system as a whole is a target for chemosensitisation.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glutathione_reductase","links":[{"label":"UniProt P00390: GSR","url":"https://www.uniprot.org/uniprotkb/P00390/entry"},{"label":"HGNC:4623 GSR","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4623"},{"label":"ChEMBL target CHEMBL2755","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL2755"}],"tags":["chembl-gap"],"related":["txnrd1"],"cancers":["glioblastoma","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":["carmustine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GSR","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 1 medicine aimed at it (Carmustine) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA GSR: RNA low tissue specificity; high antibody staining in 2 normal tissues; highest cancer staining carcinoid (2 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Brain and spinal cord tumours (all types), Lymphoma); Open Targets associates it with 4 specific cancer types at or above 0.5 (glioblastoma, plasma cell myeloma, Hodgkins lymphoma, non-Hodgkin lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas GSR tissue","url":"https://www.proteinatlas.org/ENSG00000104687-GSR/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000104687 associations","url":"https://platform.opentargets.org/target/ENSG00000104687/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4623","ensembl":"ENSG00000104687","uniprot":"P00390","entrez":"2936","firstDescribed":1977,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Krohne-Ehrich et al, Eur. J. Biochem, 1977, \"Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/923580/","biology":"A dimeric flavoenzyme using NADPH to reduce glutathione disulphide; part of the pentose phosphate and antioxidant network in every cell.","whereFound":["All cells, high in liver and red blood cells","Gliomas and lymphomas treated with carmustine"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (antioxidant recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/gsr/","neighbours":{"target":[{"id":"txnrd1","kind":"target","name":"Thioredoxin reductase 1","route":"/targets/txnrd1/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"drug":[{"id":"carmustine","kind":"drug","name":"Carmustine","route":"/drugs/carmustine/"}]}}