GSR

Summary

GSR (glutathione-disulfide reductase, HGNC:4623) is a protein-coding gene on chromosome 8p12, encoding Glutathione reductase, mitochondrial (P00390). Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH).

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.

Source: NCBI Gene 2936 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic anemia due to glutathione reductase deficiency (Strong, GenCC)
• Clinical variants (ClinVar): 251 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000637

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4623
Approved symbol	GSR
Name	glutathione-disulfide reductase
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	GRase
Ensembl gene	ENSG00000104687
Ensembl biotype	protein_coding
OMIM	138300
Entrez	2936

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000221130, ENST00000521479, ENST00000523295, ENST00000537535, ENST00000541648, ENST00000546342, ENST00000643525, ENST00000643653, ENST00000896917, ENST00000896918, ENST00000916640, ENST00000946917, ENST00000946918, ENST00000946919

RefSeq mRNA: 4 — MANE Select: NM_000637 NM_000637, NM_001195102, NM_001195103, NM_001195104

CCDS: CCDS34877, CCDS56530, CCDS56531, CCDS56532

Canonical transcript exons

ENST00000221130 — 13 exons

Exon	Start	End
ENSE00000687897	30680904	30681037
ENSE00000687899	30681930	30682061
ENSE00000687921	30700081	30700135
ENSE00001158408	30703093	30703240
ENSE00001158417	30708072	30708141
ENSE00001167123	30727530	30727846
ENSE00002132314	30678066	30679669
ENSE00003502715	30709814	30709902
ENSE00003532295	30692969	30693055
ENSE00003566136	30712062	30712088
ENSE00003568623	30689161	30689319
ENSE00003615357	30684088	30684199
ENSE00003626927	30696380	30696479

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.3295 / max 669.3664, expressed in 1822 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92633	29.6907	1818
92631	6.5615	1728
92635	5.3090	1679
92632	4.2911	1663
92630	0.3135	140
92634	0.1370	32
92626	0.0108	2
92629	0.0084	1
92627	0.0043	1
92628	0.0033	1

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	96.43	gold quality
islet of Langerhans	UBERON:0000006	96.07	gold quality
epithelium of nasopharynx	UBERON:0001951	96.01	gold quality
nasopharynx	UBERON:0001728	95.99	gold quality
renal medulla	UBERON:0000362	95.67	gold quality
pharyngeal mucosa	UBERON:0000355	95.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.40	gold quality
seminal vesicle	UBERON:0000998	95.09	gold quality
rectum	UBERON:0001052	95.01	gold quality
adrenal tissue	UBERON:0018303	94.94	gold quality
duodenum	UBERON:0002114	94.82	gold quality
palpebral conjunctiva	UBERON:0001812	94.66	gold quality
cardia of stomach	UBERON:0001162	94.51	gold quality
monocyte	CL:0000576	93.90	gold quality
jejunal mucosa	UBERON:0000399	93.67	gold quality
colonic mucosa	UBERON:0000317	93.62	gold quality
mononuclear cell	CL:0000842	93.45	gold quality
penis	UBERON:0000989	93.32	gold quality
leukocyte	CL:0000738	93.30	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.19	gold quality
tendon of biceps brachii	UBERON:0008188	93.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.13	gold quality
superior surface of tongue	UBERON:0007371	92.68	gold quality
gall bladder	UBERON:0002110	92.60	gold quality
mucosa of transverse colon	UBERON:0004991	92.38	gold quality
eye	UBERON:0000970	92.26	gold quality
colonic epithelium	UBERON:0000397	91.93	gold quality
nasal cavity mucosa	UBERON:0001826	91.90	gold quality
stromal cell of endometrium	CL:0002255	91.76	gold quality
blood	UBERON:0000178	91.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.63
E-CURD-112	no	2.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAFA, NFE2L2, PDX1, YBX3, ZBTB16

miRNA regulators (miRDB)

65 targeting GSR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3975	99.62	65.97	697

Literature-anchored findings (GeneRIF, showing 30)

• Malignant lung tumors (squamous cell carcinoma and adenocarcinoma) had increased activity of this enzyme. (PMID:12447480)
• activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were decreased during intense physical exercise (PMID:12516882)
• An oxidative stress marker after kidney transplantation (PMID:12826156)
• Patients with chronic alcoholism (PCA) of stage II have increased glutathione reductase (GR) activity in neutrophils, lymphocytes and monocytes compared with that in the cells of healthy donors (PMID:12838767)
• GR activity in COPD and chest osteomyelitis decreased by 40% and more, lung tumors–by 32-36%. (PMID:12838770)
• serum concentrations in patients with chronic lymphocytic leukemia (PMID:14637279)
• No statistically significant differences for glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, and glutathione reductase were encountered between normal values and those of asthenozoospermic patients. (PMID:15149466)
• Decreased activities of erythrocyte glutathione reductase is associated with cerebral palsy (PMID:15978628)
• Data show that both glutathione and glutathione reductase are inducible by D3T, and that upregulation of GSH biosynthesis underlies D3T-mediated cytoprotection against ROS/RNS-elicited injury to human vascular smooth muscle cells. (PMID:17206382)
• Inhibitory effects of several antibiotics on purified human erythrocyte glutathione reductase has been investigated. (PMID:18341267)
• Data report synchrotron-based cryocrystallographic studies of natural substrate complexes of the flavoenzyme human glutathione reductase at nominal resolutions between 1.1 and 0.95 A that reveal new aspects of its mechanism. (PMID:18638483)
• higher glutathione reductase and total antioxidant capacity were found in end-stage renal disease patients than in controls (PMID:19377255)
• Data show that decreased activities of GPX1, increased activities of GR and CuZnSOD in women with depressive disorder. (PMID:19527700)
• An increase in the activities of superoxide dismutase was observed in patients with active and silent celiac disease, while the activities of glutathione peroxidase and glutathione reductase and the glutathione content were significantly reduced. (PMID:19560448)
• GR deficiency and drug-induced GR inhibition may protect from malaria by inducing enhanced ring stage phagocytosis rather than by impairing parasite growth directly [case study] (PMID:19806191)
• Human eye lenses were dissected into discrete regions that were formed at different stages of life and assayed for activity of lactate dehydrogenase (LDH) and a particularly stable enzyme, glutathione reductase (GR). (PMID:20586645)
• novel glutathione reductase alternative splice variants (PMID:20628807)
• Up-regulation of CAT and GR activity resulted in an increase in total antioxidant activity in A549 after exposure to B(a)P. (PMID:21417634)
• The results demonstrate for the first time that glutathione reductase gene polymorphisms are significantly associated with bone mineral density. (PMID:22089180)
• GSR was the most significant single SNP association with systemic lupus erythematosus in African Americans. (PMID:23637325)
• 1,25 (OH) vitamin D significantly upregulated expression of GCLC and GR and lowered secretion of IL-8 and MCP-1 in high-glucose exposed U937 monocytes. (PMID:23770363)
• Glutathione reductase reduces mitochondrial protein mitoNEET [2Fe-2S] clusters. (PMID:25645953)
• 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. (PMID:26316444)
• 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. (PMID:26419038)
• 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. (PMID:28693341)
• 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. (PMID:29105080)
• 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. (PMID:31530934)
• Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome. (PMID:34090318)
• MicroRNA-362-5p promotes the proliferation and inhibits apoptosis of trophoblast cells via targeting glutathione-disulfide reductase. (PMID:34107852)
• Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases. (PMID:35361806)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gsr	ENSDARG00000019236
mus_musculus	Gsr	ENSMUSG00000031584
rattus_norvegicus	Gsr	ENSRNOG00000014915
caenorhabditis_elegans		WBGENE00008117

Paralogs (7): DLD (ENSG00000091140), PYROXD1 (ENSG00000121350), AIFM1 (ENSG00000156709), AIFM3 (ENSG00000183773), TXNRD2 (ENSG00000184470), TXNRD3 (ENSG00000197763), TXNRD1 (ENSG00000198431)

Protein

Protein identifiers

Glutathione reductase, mitochondrial — P00390 (reviewed: P00390)

All UniProt accessions (4): A0A2R8YF59, P00390, H0YC68, V9HW90

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH). Constitutes the major mechanism to maintain a high GSH:GSSG ratio in the cytosol.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Mitochondrion Cytoplasm.

Disease relevance. Anemia, congenital, non-spherocytic hemolytic, 10 (CNSHA10) [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. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 FAD per subunit.

Domain organisation. 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.

Miscellaneous. The active site is a redox-active disulfide bond. Produced by alternative initiation of isoform Mitochondrial. Expressed at very high levels in peripheral blood.

Similarity. Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P00390-1	Mitochondrial	yes
P00390-2	Cytoplasmic
P00390-3	2, delta8
P00390-4	3, delta9
P00390-5	4, delta8+9

RefSeq proteins (4): NP_000628, NP_001182031, NP_001182032, NP_001182033 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001100	Pyr_nuc-diS_OxRdtase	Family
IPR004099	Pyr_nucl-diS_OxRdtase_dimer	Domain
IPR006322	Glutathione_Rdtase_euk/bac	Family
IPR012999	Pyr_OxRdtase_I_AS	Active_site
IPR016156	FAD/NAD-linked_Rdtase_dimer_sf	Homologous_superfamily
IPR023753	FAD/NAD-binding_dom	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR046952	GSHR/TRXR-like	Family

Pfam: PF02852, PF07992

Enzyme classification (BRENDA):

• EC 1.8.1.7 — glutathione-disulfide reductase (BRENDA: 93 organisms, 190 substrates, 388 inhibitors, 212 Km, 68 kcat entries)

Substrate kinetics (BRENDA)

37 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.0015–0.27	61
GLUTATHIONE DISULFIDE	0.0017–2.31	42
GSSG	0.0045–7	42
GLUTATHIONE	0.023–8.2	13
NADH	0.017–1.12	10
TRYPANOTHIONE	0.21–4.58	7
NADP+	0.03–0.22	3
1,4-NAPHTHOQUINONE	0.158–0.172	2
5,5’-DITHIOBIS(2-NITROBENZOIC ACID)	0.114–0.71	2
6,7-DIMETHYLQUINOLINE-5,8-DIONE	0.0858–0.413	2
6-METHYLQUINOLINE-5,8-DIONE	0.4104–0.4208	2
7-METHYLQUINOLINE-5,8-DIONE	0.224–0.404	2
FAD	0.0005–0.0008	2
MENADIONE	0.0312–0.0822	2
QUINOLINE-5,8-DIONE	0.234–0.363	2

Catalyzed reactions (Rhea), 1 shown:

• 2 glutathione + NADP(+) = glutathione disulfide + NADPH + H(+) (RHEA:11740)

UniProt features (85 total): strand 25, binding site 22, helix 17, sequence variant 8, turn 4, splice variant 3, disulfide bond 2, transit peptide 1, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
3DK9	X-RAY DIFFRACTION	0.95
3DJJ	X-RAY DIFFRACTION	1.1
3DK8	X-RAY DIFFRACTION	1.1
3DK4	X-RAY DIFFRACTION	1.2
3GRS	X-RAY DIFFRACTION	1.54
1DNC	X-RAY DIFFRACTION	1.7
1GSN	X-RAY DIFFRACTION	1.7
2GH5	X-RAY DIFFRACTION	1.7
3DJG	X-RAY DIFFRACTION	1.8
1GRB	X-RAY DIFFRACTION	1.85
1K4Q	X-RAY DIFFRACTION	1.9
1GRA	X-RAY DIFFRACTION	2
1GRE	X-RAY DIFFRACTION	2
1GRF	X-RAY DIFFRACTION	2
1GRG	X-RAY DIFFRACTION	2
1XAN	X-RAY DIFFRACTION	2
1BWC	X-RAY DIFFRACTION	2.1
3SQP	X-RAY DIFFRACTION	2.21
1GRT	X-RAY DIFFRACTION	2.3
4GR1	X-RAY DIFFRACTION	2.4
5GRT	X-RAY DIFFRACTION	2.4
3GRT	X-RAY DIFFRACTION	2.5
2AAQ	X-RAY DIFFRACTION	2.6
2GRT	X-RAY DIFFRACTION	2.7
4GRT	X-RAY DIFFRACTION	2.8
1GRH	X-RAY DIFFRACTION	3
1ALG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00390-F1	91.77	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 511 (proton acceptor)

Ligand- & substrate-binding residues (22): 110; 158; 174; 239; 242; 245; 262; 268; 334; 375; 381; 383 …

Post-translational modifications (1): 97

Disulfide bonds (2): 102–107, 134

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2408550	Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 271 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, HORIUCHI_WTAP_TARGETS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, LU_IL4_SIGNALING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, TTGCWCAAY_CEBPB_02, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_CELL_REDOX_HOMEOSTASIS, GOBP_AMIDE_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN

GO Biological Process (4): glutathione metabolic process (GO:0006749), cellular response to oxidative stress (GO:0034599), cell redox homeostasis (GO:0045454), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (7): glutathione-disulfide reductase (NADPH) activity (GO:0004362), electron transfer activity (GO:0009055), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), nucleotide binding (GO:0000166), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor (GO:0016668)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), external side of plasma membrane (GO:0009897), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Selenoamino acid metabolism	1
Cellular response to chemical stress	1
Metabolism of nucleotides	1
Transcriptional Regulation by TP53	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
response to oxidative stress	1
cellular response to chemical stress	1
cellular homeostasis	1
cellular detoxification	1
glutathione disulfide oxidoreductase activity	1
antioxidant activity	1
oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	1
molecular_function	1
nucleotide binding	1
anion binding	1
adenyl nucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
plasma membrane	1
cell surface	1
side of membrane	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSR	GPX5	O75715	973
GSR	GPX2	P18283	970
GSR	GPX8	Q8TED1	970
GSR	GPX7	Q96SL4	968
GSR	GLRX	P35754	967
GSR	GPX6	P59796	967
GSR	GPX3	P22352	955
GSR	G6PD	P11413	917
GSR	H6PD	O95479	912
GSR	GRIA4	P48058	896
GSR	TXN	P10599	892
GSR	NQO1	P15559	820
GSR	GRIA1	P42261	817
GSR	GCLC	P48506	811
GSR	SOD2	P04179	800

IntAct

42 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
MPHOSPH6	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
TPD52L1	TPD52L2	psi-mi:“MI:0914”(association)	0.530
	DENR	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
CSTPP1	GSR	psi-mi:“MI:0915”(physical association)	0.370
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
SMARCB1		psi-mi:“MI:0914”(association)	0.350
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DNAJC30	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MARS2	DDX39A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPS12	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	UBA6	psi-mi:“MI:0914”(association)	0.350
PCGF6	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
SKP1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
SNRNP27	BPNT1	psi-mi:“MI:0914”(association)	0.350
TEX264	GSR	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): AIFM1 (Co-fractionation), ASS1 (Co-fractionation), GSR (Co-fractionation), GSR (Co-fractionation), LSM12 (Co-fractionation), TOMM40 (Co-fractionation), GSR (Affinity Capture-MS), GSR (Affinity Capture-MS), GSR (Proximity Label-MS), GSR (Affinity Capture-MS), GSR (Affinity Capture-MS), GSR (Affinity Capture-MS), GSR (Affinity Capture-MS), GSR (Affinity Capture-MS), GSR (Co-fractionation)

ESM2 similar proteins: A0A0P0UZP7, A0A0P0V5U9, A0A0P0WIY3, A2TIL1, A2WYS7, A2WYS8, A3BLS0, B6TNK6, B8ANW0, C0PBF8, O23024, O49312, O64489, P00390, P0C0M2, P51108, Q0D4Z6, Q0DGU2, Q0IP69, Q0JG98, Q0JG99, Q10RE2, Q10S72, Q1JPL4, Q53QK0, Q5W6F9, Q60EJ6, Q60EY8, Q69PS6, Q69RG7, Q6Z9F4, Q6ZD89, Q6ZLA3, Q7XQ85, Q7ZW24, Q8BWN8, Q8RZA1, Q8VZ59, Q94BP3, Q9FM04

Diamond homologs: A2TIL1, B9A1H3, D0VWY5, D9J041, O04955, O15770, O34324, O62768, O89049, P00390, P06715, P0A0E4, P0A0E5, P13110, P16171, P23189, P27456, P28593, P30635, P35484, P39040, P39050, P39051, P39916, P41921, P42770, P43783, P47791, P48638, P48639, P48640, P48641, P48642, P61076, P70619, P78965, P80461, P80647, P85207, P91938

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKAA1	“up-regulates activity”	GSR	phosphorylation
NFE2L2	“up-regulates quantity by expression”	GSR	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

251 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	129
Likely benign	48
Benign	35

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4770668	NM_000637.5(GSR):c.640+1del	Pathogenic
694660	NM_000637.5(GSR):c.1286-229_*499del	Pathogenic
694661	NM_000637.5(GSR):c.993G>A (p.Trp331Ter)	Pathogenic
694662	NM_000637.5(GSR):c.1121G>C (p.Gly374Ala)	Pathogenic
3065567	NM_000637.5(GSR):c.342del (p.Met113_Trp114insTer)	Likely pathogenic
3065853	NM_000637.5(GSR):c.640G>A (p.Gly214Ser)	Likely pathogenic
4849357	NM_000637.5(GSR):c.70C>T (p.Arg24Ter)	Likely pathogenic

SpliceAI

1896 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30679666:CCAC:C	acceptor_gain	1.0000
8:30679667:CACC:C	acceptor_gain	1.0000
8:30680901:TA:T	donor_loss	1.0000
8:30680903:C:CT	donor_loss	1.0000
8:30681033:TTCAT:T	acceptor_gain	1.0000
8:30681034:TCAT:T	acceptor_gain	1.0000
8:30681035:CAT:C	acceptor_gain	1.0000
8:30681035:CATC:C	acceptor_gain	1.0000
8:30681036:AT:A	acceptor_gain	1.0000
8:30681038:C:CC	acceptor_gain	1.0000
8:30681038:C:CG	acceptor_loss	1.0000
8:30681039:T:A	acceptor_loss	1.0000
8:30681041:CAA:C	acceptor_gain	1.0000
8:30681043:A:AC	acceptor_gain	1.0000
8:30681043:A:C	acceptor_gain	1.0000
8:30681046:C:CT	acceptor_gain	1.0000
8:30681927:TACC:T	donor_loss	1.0000
8:30681928:A:AT	donor_loss	1.0000
8:30681928:ACCTT:A	donor_gain	1.0000
8:30681929:CCTTC:C	donor_gain	1.0000
8:30682059:CAA:C	acceptor_gain	1.0000
8:30682062:C:CC	acceptor_gain	1.0000
8:30684086:A:AC	donor_gain	1.0000
8:30684086:A:C	donor_loss	1.0000
8:30684087:C:CC	donor_gain	1.0000
8:30684087:C:G	donor_loss	1.0000
8:30684195:ATCCC:A	acceptor_gain	1.0000
8:30684196:TCCC:T	acceptor_gain	1.0000
8:30684197:CCC:C	acceptor_gain	1.0000
8:30684197:CCCC:C	acceptor_gain	1.0000

AlphaMissense

3412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30679558:G:C	H511D	1.000
8:30681967:G:C	F416L	1.000
8:30681967:G:T	F416L	1.000
8:30681969:A:G	F416L	1.000
8:30712076:A:G	C107R	1.000
8:30679533:A:T	V519D	0.999
8:30679541:T:A	E516D	0.999
8:30679541:T:G	E516D	0.999
8:30679542:T:A	E516V	0.999
8:30679554:G:T	P512H	0.999
8:30679556:G:C	H511Q	0.999
8:30679556:G:T	H511Q	0.999
8:30679557:T:C	H511R	0.999
8:30679566:A:T	V508D	0.999
8:30679586:C:A	K501N	0.999
8:30679586:C:G	K501N	0.999
8:30679608:G:T	A494E	0.999
8:30679611:A:T	V493D	0.999
8:30679620:C:T	G490D	0.999
8:30679621:C:G	G490R	0.999
8:30679662:C:T	G476E	0.999
8:30679663:C:A	G476W	0.999
8:30679663:C:G	G476R	0.999
8:30679663:C:T	G476R	0.999
8:30680982:A:C	F447L	0.999
8:30680982:A:T	F447L	0.999
8:30680984:A:G	F447L	0.999
8:30681032:C:G	A431P	0.999
8:30681941:C:T	G425E	0.999
8:30681942:C:G	G425R	0.999

dbSNP variants (sampled 300 via entrez): RS1000006113 (8:30726044 A>G), RS1000014435 (8:30718224 T>C), RS1000065782 (8:30729652 C>G), RS1000163907 (8:30686614 G>C), RS1000179040 (8:30729304 C>T), RS1000230025 (8:30728099 G>C), RS1000406087 (8:30695381 C>G), RS1000407713 (8:30722498 G>A), RS1000415271 (8:30724129 T>C), RS1000504955 (8:30687162 G>A), RS1000511507 (8:30728527 G>A), RS1000609067 (8:30694512 C>A,T), RS1000635934 (8:30688630 G>A), RS1000692938 (8:30678875 C>A), RS1000704509 (8:30679030 T>G)

Disease associations

OMIM: gene MIM:138300 | disease phenotypes: MIM:618660

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic anemia due to glutathione reductase deficiency	Strong	Autosomal recessive

Mondo (1): hemolytic anemia due to glutathione reductase deficiency (MONDO:0019531)

Orphanet (1): Hemolytic anemia due to glutathione reductase deficiency (Orphanet:90030)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000518	Cataract
HP:0002904	Hyperbilirubinemia
HP:0004814	Fava bean-induced hemolytic anemia
HP:6000525	Reduced erythrocyte glutathione reductase activity

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2755 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,300,394 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	113,934
CHEMBL513	CARMUSTINE	4	148,550
CHEMBL590	MENADIONE	4	21,034
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL8085	LYSINE	2	988,081

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3594	Toxicity	3	carboplatin;taxanes	Ovarian Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3594	GSR	3	3.50	1	carboplatin;taxanes

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
carmustine	Inhibition	4.15	pIC50

Binding affinities (BindingDB)

6 measured of 9 human assays (9 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S(R),7R(S))-7-Hydroxybicyclo[2.2.1]heptan-2-yl nitrate	IC50	7130 nM
(Z)-2-butenedioate;10-(1-methyl-4-piperidinylidene)-5H-benzo[1,2]cyclohepta[3,4-b]thiophen-4-one	KI	8300 nM
4-Hydroxy-1,1-dioxo-1,2-dihydro-1lambda6-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide	KI	10100 nM
640/359	KI	32700 nM
CEFOPERAZONE	KI	245000 nM
Gadopentetic acid	KI	7.34e+07 nM

ChEMBL bioactivities

46 potent at pChembl≥5 of 114 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	2-(2-Amino-ethylamino)-N-(7-{2-[N’-(5-nitro-furan-2-carbonyl)-hydrazino]-2-oxo-ethyl}-naphthalen-2-yl)-acetamide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
8.39	IC50	4.1	nM	CHEMBL120147
6.68	Ki	211	nM	CHEMBL1824793
6.46	IC50	344	nM	CHEMBL1824793
6.23	IC50	590	nM	CHEMBL5425052
6.12	IC50	750	nM	CHEMBL135536
6.00	IC50	1000	nM	CHEMBL39225
6.00	IC50	1000	nM	CHEMBL287849
6.00	IC50	1000	nM	CHEMBL39137
6.00	IC50	1000	nM	CHEMBL135504
5.75	IC50	1800	nM	CHEMBL135287
5.70	IC50	2000	nM	CHEMBL39084
5.70	IC50	2000	nM	CHEMBL287955
5.64	IC50	2300	nM	CHEMBL5402846
5.60	IC50	2500	nM	CHEMBL39051
5.58	IC50	2600	nM	CHEMBL135287
5.57	IC50	2700	nM	CHEMBL135287
5.57	IC50	2700	nM	CHEMBL134615
5.52	IC50	3000	nM	CHEMBL290232
5.50	IC50	3200	nM	CHEMBL135287
5.46	IC50	3500	nM	CHEMBL39449
5.46	IC50	3500	nM	CHEMBL290422
5.43	Ki	3700	nM	CHEMBL135287
5.43	IC50	3700	nM	CHEMBL5401123
5.40	IC50	4000	nM	CHEMBL38899
5.38	Ki	4160	nM	CHEMBL1824791
5.34	Ki	4570	nM	CHEMBL1824792
5.30	IC50	5000	nM	CHEMBL224976
5.30	IC50	5000	nM	CHEMBL39270
5.17	IC50	6810	nM	CHEMBL1094857
5.16	IC50	7000	nM	CHEMBL415870
5.15	IC50	7130	nM	CHEMBL1094856
5.14	IC50	7170	nM	CHEMBL556671
5.12	IC50	7600	nM	CORULEOELLAGIC ACID
5.10	IC50	8000	nM	CHEMBL39829
5.10	IC50	8000	nM	CHEMBL38563
5.09	IC50	8100	nM	CARMUSTINE
5.09	IC50	8100	nM	CHEMBL561220
5.06	IC50	8710	nM	CHEMBL561901
5.06	IC50	8760	nM	CHEMBL5818041
5.05	Kd	8809	nM	CHEMBL3752910
5.05	ED50	8809	nM	CHEMBL3752910
5.02	IC50	9600	nM	CHEMBL5426441
5.00	IC50	1e+04	nM	MOLIBRESIB
5.00	IC50	9900	nM	CHEMBL92155

PubChem BioAssay actives

50 with measured affinity, of 345 total; 44 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N’-(2-naphthalen-2-ylacetyl)-5-nitrofuran-2-carbohydrazide	254839: Inhibitory concentration against human glutathione reductase	ic50	0.0041	uM
(2S)-2-[(4-nitrobenzoyl)amino]pentanedioic acid	617312: Competitive inhibition of human erythrocyte Glutathione reductase using GSSG substrate by Lineweaver-Burk plot analysis	ki	0.2110	uM
4-[4-[[2-fluoro-4-[(E)-3-(3-nitrophenyl)prop-2-enoyl]phenoxy]methyl]triazol-1-yl]butyl-triphenylphosphanium	1973368: Inhibition of glutathione reductase (unknown origin)	ic50	0.5900	uM
6-(8-hydroxy-3-methyl-1,4-dioxonaphthalen-2-yl)hexanoic acid	75300: In vitro inhibition of human Glutathione Reductase	ic50	0.7500	uM
Ketotifen	1803039: Activity Assay from Article 10.3109/14756366.2011.572879: “In vitro effects of some drugs on human erythrocyte glutathione reductase.”	ki	0.8000	uM
5-(8-hydroxy-3-methyl-1,4-dioxonaphthalen-2-yl)pentanoic acid	75300: In vitro inhibition of human Glutathione Reductase	ic50	1.0000	uM
10-(4-chlorophenyl)-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
10-(4-chlorophenyl)benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
10-(3,5-dichlorophenyl)-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
3-methyl-10-[3-(trifluoromethyl)phenyl]benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
10-(3,5-dichlorophenyl)benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
10-[3-(trifluoromethyl)phenyl]benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
10-(4-chlorophenyl)-8-fluoro-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
3-methyl-10-(2,3,4,5,6-pentafluorophenyl)benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	1.0000	uM
6-(3-methyl-1,4-dioxonaphthalen-2-yl)hexanoic acid	242621: Inhibitory concentration against human glutathione reductase in the absence of glucose-6-phosphate dehydrogenase (G6PDH)	ic50	1.8000	uM
3-methyl-10-phenylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	2.0000	uM
3-methyl-10-naphthalen-1-ylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	2.0000	uM
4-[(3,4-dichlorophenyl)methyl]-N-(4-fluorophenyl)-N-[[5-[2-(4-fluorophenyl)ethylcarbamoyl]furan-2-yl]methyl]-4-(3-phenylpropyl)piperazin-4-ium-1-carboxamide iodide	1993002: Inhibition of human glutathione reductase expressed in Escherichia coli cells using trypanothione as substrate preincubated for 3 mins followed NADPH addition by spectrophotometric analysis	ic50	2.3000	uM
8-azido-10-(4-chlorophenyl)-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	2.5000	uM
5-(3-methyl-1,4-dioxonaphthalen-2-yl)pentanoic acid	75300: In vitro inhibition of human Glutathione Reductase	ic50	2.7000	uM
3-methyl-10-pyridin-4-ylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	3.0000	uM
10-(2,3,4,5,6-pentafluorophenyl)benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	3.5000	uM
10-[3,5-bis(trifluoromethyl)phenyl]benzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	3.5000	uM
4-[(3,4-dichlorophenyl)methyl]-N-[[5-[2-(4-fluorophenyl)ethylcarbamoyl]furan-2-yl]methyl]-4-(3-phenylpropyl)piperazin-4-ium-1-carboxamide iodide	1993002: Inhibition of human glutathione reductase expressed in Escherichia coli cells using trypanothione as substrate preincubated for 3 mins followed NADPH addition by spectrophotometric analysis	ic50	3.7000	uM
10-anthracen-1-yl-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	4.0000	uM
(4-nitrophenyl) (2S)-6-[(2-chlorophenyl)methoxycarbonylamino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate	617313: Non-Competitive inhibition of human erythrocyte Glutathione reductase using GSSG substrate by Lineweaver-Burk plot analysis	ki	4.1600	uM
(2R)-2-[(4-nitrophenyl)methylamino]butan-1-ol	617312: Competitive inhibition of human erythrocyte Glutathione reductase using GSSG substrate by Lineweaver-Burk plot analysis	ki	4.5700	uM
(1E)-1-(2-chlorophenyl)penta-1,4-dien-3-one	282990: Inhibition of human glutathione reductase after 5 mins pre-incubation with NADPH in presence of 500 uM GSSG substrate	ic50	5.0000	uM
10-[3,5-bis(trifluoromethyl)phenyl]-3-methylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	5.0000	uM
Meloxicam	1803039: Activity Assay from Article 10.3109/14756366.2011.572879: “In vitro effects of some drugs on human erythrocyte glutathione reductase.”	ki	6.1000	uM
[(2R,7R)-7-hydroxy-2-bicyclo[2.2.1]heptanyl] nitrate	420294: Inhibition of human erythrocyte glutathione reductase	ic50	6.8100	uM
ethyl 2-[10-(3,5-dichlorophenyl)-2,4-dioxobenzo[g]pteridin-3-yl]acetate	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	7.0000	uM
[(2S,7R)-7-hydroxy-2-bicyclo[2.2.1]heptanyl] nitrate	420294: Inhibition of human erythrocyte glutathione reductase	ic50	7.1300	uM
(2,3-dihydroxy-4-nitrooxycyclohexyl) nitrate	420294: Inhibition of human erythrocyte glutathione reductase	ic50	7.1700	uM
3,5,6,10,12,13-hexahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),3,5,8(16),10,12-hexaene-7,14-dione	580672: Inhibition of human glutathione reductase by spectrophotometer	ic50	7.6000	uM
ethyl 2-[2,4-dioxo-10-[3-(trifluoromethyl)phenyl]benzo[g]pteridin-3-yl]acetate	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	8.0000	uM
3-methyl-10-pyridin-3-ylbenzo[g]pteridine-2,4-dione	75301: Inhibitory activity against human glutathione reductase in presence of 100 uM GSSG	ic50	8.0000	uM
Carmustine	1062975: Inhibition of human recombinant glutathione reductase using glutathione as substrate preincubated for 30 mins by colorimetric assay	ic50	8.1000	uM
(2,4-dihydroxy-5-nitrooxycyclohexyl) nitrate	420294: Inhibition of human erythrocyte glutathione reductase	ic50	8.1000	uM
(2,5-dihydroxy-4-nitrooxycyclohexyl) nitrate	420294: Inhibition of human erythrocyte glutathione reductase	ic50	8.7100	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148466: Binding affinity to human GSR incubated for 45 mins by Kinobead based pull down assay	kd	8.8085	uM
4-[3-(2-chlorophenothiazin-10-yl)propyl]-N-(4-fluorophenyl)-N-[[5-[2-(4-fluorophenyl)ethylcarbamoyl]furan-2-yl]methyl]piperazine-1-carboxamide	1993002: Inhibition of human glutathione reductase expressed in Escherichia coli cells using trypanothione as substrate preincubated for 3 mins followed NADPH addition by spectrophotometric analysis	ic50	9.6000	uM
N-[2-[(6-chloro-2-methoxyacridin-9-yl)amino]ethyl]naphthalene-2-sulfonamide	75303: Inhibitory concentration against human Glutathione reductase was determined	ic50	9.9000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178902: Inhibition of GSR (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

268 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, increases activity, decreases activity (+3 more)	15
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	8
bisphenol A	affects expression, affects cotreatment, increases expression, decreases expression, decreases methylation	7
Benzo(a)pyrene	affects cotreatment, increases activity, decreases reaction, decreases activity, increases expression (+1 more)	7
Carmustine	decreases activity, increases response to substance, decreases reaction, affects reaction	7
Cadmium Chloride	decreases expression, increases expression, decreases reaction, decreases activity	6
tert-Butylhydroperoxide	decreases reaction, increases activity, decreases methylation, increases expression	6
Resveratrol	affects cotreatment, increases expression, increases activity	5
Arsenic Trioxide	increases abundance, increases expression, decreases response to substance, affects cotreatment, decreases expression	5
Arsenic	increases expression, increases abundance, affects cotreatment	4
Cisplatin	affects cotreatment, increases expression, decreases activity, increases reaction	4
Dexamethasone	affects localization, increases expression, affects cotreatment	4
Quercetin	decreases reaction, increases activity, increases expression	4
Particulate Matter	increases abundance, decreases activity, decreases expression	4
bisphenol F	affects cotreatment, increases expression	3
sodium arsenate	increases abundance, increases expression, affects cotreatment, increases reduction, decreases expression (+1 more)	3
sulforaphane	decreases activity, increases expression	3
salvin	increases reaction, decreases expression, decreases reaction, increases expression	3
Aerosols	increases expression	3
Ascorbic Acid	affects cotreatment, affects metabolic processing, decreases reaction, increases activity, decreases activity	3
Vehicle Emissions	decreases activity, decreases expression, increases abundance, increases expression	3
Hydrogen Peroxide	decreases reaction, increases activity, affects expression	3
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	3
Paraquat	decreases activity, decreases reaction, increases expression, affects cotreatment	3
Plant Extracts	increases expression, decreases activity, decreases reaction, affects cotreatment	3
Valproic Acid	increases expression	3
protocatechualdehyde	decreases activity, decreases reaction	2
2-tert-butylhydroquinone	increases activity, decreases activity, decreases reaction	2
perfluorooctanoic acid	increases activity, increases expression	2
manganese chloride	decreases expression, increases abundance, increases expression, affects cotreatment	2

ChEMBL screening assays

114 unique, capped per target: 108 binding, 5 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023583	Binding	Activity at human recombinant glutathione reductase at pH 6.9	Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum. — Antimicrob Agents Chemother
CHEMBL2114855	Functional	PubChem BioAssay. qHTS Assay for Inhibitors of Mammalian Selenoprotein Thioredoxin Reductase 1 (TrxR1): Counter assay in Glutathione Reductase (GR). (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL5346005	Toxicity	Inhibition of human glutathione reductase expressed in Escherichia coli cells using trypanothione as substrate preincubated for 3 mins followed NADPH addition by spectrophotometric analysis	Fragment Merging, Growing, and Linking Identify New Trypanothione Reductase Inhibitors for Leishmaniasis. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8H1	Abcam HCT 116 GSR KO	Cancer cell line	Male
CVCL_B8WG	Abcam MCF-7 GSR KO	Cancer cell line	Female
CVCL_B9JB	Abcam A-549 GSR KO	Cancer cell line	Male
CVCL_SQ69	HAP1 GSR (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.