GSTA1

Summary

GSTA1 (glutathione S-transferase alpha 1, HGNC:4626) is a protein-coding gene on chromosome 6p12.2, encoding Glutathione S-transferase A1 (P08263). Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds.

This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2938 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 38 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_145740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4626
Approved symbol	GSTA1
Name	glutathione S-transferase alpha 1
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000243955
Ensembl biotype	protein_coding
OMIM	138359
Entrez	2938

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334575, ENST00000476213, ENST00000493331, ENST00000867629, ENST00000867630, ENST00000867631, ENST00000867632, ENST00000867633, ENST00000867634, ENST00000867635, ENST00000867636

RefSeq mRNA: 2 — MANE Select: NM_145740 NM_001319059, NM_145740

CCDS: CCDS4945

Canonical transcript exons

ENST00000334575 — 7 exons

Exon	Start	End
ENSE00002462346	52803785	52803816
ENSE00003464845	52794125	52794266
ENSE00003467843	52797586	52797637
ENSE00003638642	52799181	52799297
ENSE00003649176	52792856	52792987
ENSE00003659041	52796182	52796314
ENSE00003842469	52791371	52791980

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.5279 / max 1069.8387, expressed in 137 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73974	4.5279	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.86	gold quality
epithelium of bronchus	UBERON:0002031	99.86	gold quality
jejunal mucosa	UBERON:0000399	99.78	gold quality
right adrenal gland	UBERON:0001233	99.72	gold quality
right adrenal gland cortex	UBERON:0035827	99.61	gold quality
left adrenal gland cortex	UBERON:0035825	99.58	gold quality
adrenal tissue	UBERON:0018303	99.52	gold quality
epithelium of nasopharynx	UBERON:0001951	99.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.40	gold quality
bronchus	UBERON:0002185	99.39	gold quality
adrenal cortex	UBERON:0001235	99.34	gold quality
nasal cavity epithelium	UBERON:0005384	99.32	gold quality
left adrenal gland	UBERON:0001234	99.31	gold quality
adult organism	UBERON:0007023	99.23	gold quality
duodenum	UBERON:0002114	98.99	gold quality
ileal mucosa	UBERON:0000331	98.92	gold quality
renal glomerulus	UBERON:0000074	98.56	gold quality
right testis	UBERON:0004534	98.55	gold quality
gall bladder	UBERON:0002110	98.51	gold quality
right lobe of liver	UBERON:0001114	98.47	gold quality
kidney epithelium	UBERON:0004819	98.46	gold quality
metanephric glomerulus	UBERON:0004736	98.39	gold quality
liver	UBERON:0002107	98.13	gold quality
adrenal gland	UBERON:0002369	98.09	gold quality
left testis	UBERON:0004533	98.02	gold quality
islet of Langerhans	UBERON:0000006	97.90	gold quality
adult mammalian kidney	UBERON:0000082	97.86	gold quality
nephron tubule	UBERON:0001231	97.71	gold quality
testis	UBERON:0000473	97.20	gold quality
body of pancreas	UBERON:0001150	96.67	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	11528.24
E-MTAB-8495	yes	7693.47
E-MTAB-10553	yes	4355.17
E-GEOD-125970	yes	3687.68
E-GEOD-134144	yes	2650.94
E-MTAB-9906	yes	1636.43
E-HCAD-9	yes	1499.44
E-ENAD-27	yes	1003.41
E-HCAD-1	yes	25.90
E-GEOD-81547	yes	23.18
E-MTAB-5061	yes	20.88
E-GEOD-130148	yes	13.60
E-HCAD-31	yes	5.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, HNF1B, NFE2L2, TP53

miRNA regulators (miRDB)

28 targeting GSTA1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-198	98.70	67.32	920
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6069	97.45	65.88	357
HSA-MIR-5681B	94.82	69.30	514

Literature-anchored findings (GeneRIF, showing 40)

• low level of expression seen in prostatic intraepithelial neoplasia and prostate adenocarcinoma, suggesting lack of detoxification activity that may be associated with carcinogenesis (PMID:11550208)
• Polymorphism identified in the proximal promoter of GSTA1 correlate with its expression in the liver and is expected to be of significance for individual risk of cancer or individual response to chemotherapeutic agents. (PMID:11692074)
• Deletion of Glu alpha-carboxylate from the substrate glutathione causes a drastic loss in the catalytic efficiency of GST A1-1, probably due to a combination of lowered affinity for the thiol substrate and raised pKa of the active-site-bound thiol group. (PMID:11747461)
• ability of the two Alpha class subunit interfaces to adopt a functional heterodimeric structure (PMID:11851347)
• Thermodynamics of the ligandin function of human class Alpha glutathione transferase A1-1: energetics of organic anion ligand binding. (GSTA1-1) (PMID:11931663)
• expression of hGSTA1/2 and hGSTA4 steady-state mRNAs in second trimester prenatal livers (PMID:12093480)
• expressed at high levels in duodenum and small intestine and expression decreased from proximal to distal small intestine (PMID:12139976)
• Kinetic studies with completely glutathiolated GST A1-1 indicate that modification at cysteine-112 has no effect on catalytic turnover of the isoenzyme or the binding of nonsubstrate ligands. (PMID:12206662)
• X-ray Crystallography model of GSTA1 bound with S-hexyl glutathione bound reveals possible extended ligandin binding site. (PMID:12211029)
• Malignant lung tumors(squamous cell carcinoma and adenocarcinoma) had significantly increased levels of this enzyme. (PMID:12447480)
• presence of glutathione S-transferases A1-1 and P1-1 in seminal fluid suggests a role in the protection against (oxidative) damage of spermatozoa (PMID:12524083)
• dinitrosyl-diglutathionyl-iron complex, a natural carrier of nitric oxide, binds with extraordinary affinity to GSTA1-1, which is explained by molecular modeling and related to molecular evolution (PMID:12871945)
• Isoleucine-219 mutation to alanine results in a positional displacement of the carboxy-terminal region in GSTA1-1 having fewer interactions with the protein and, thus, diminished stability and reduction in catalytic function. (PMID:14690442)
• Addition of glutathione (GSH) causes glutathione transferase A1-1 to become a stable alpha-helix (PMID:15182170)
• The frequency of the GSTA1*B allele in a Japanese population was found to be 16.0%. (PMID:15202795)
• GSTA1 polymorphisms are associated with prostate cancer susceptibility, especially among smokers. (PMID:15616829)
• Disruption of the N-capping motif of helix 9 alters the conformational dynamics of the C-terminal region and, consequently, the features of the H-site to which hydrophobic substrates bind. (PMID:15757902)
• The frequency of GSTA1 *A/*B or *B/*B genotype was 24.3% in urothelial cancer cases, compared with 21.2% in the control groups (OR=1.22; 95%CI 0.87-1.72) after adjustment for age, gender and smoking status. (PMID:15797627)
• crystal structure; mobile C-terminal region in apo human GSTA1-1 is structured and does not undergo ligand-induced folding (PMID:15893769)
• communication between the two active sites of dimeric glutathione S-transferase A1-1 (PMID:15952767)
• Both Met51 and Phe52 in the intersubunit lock-and-key motif play important structural roles in maintaining the catalytic and ligandin functions and stability of the GST dimer. (PMID:16190865)
• distribution of hGSTA1 gene is polymorphic in Chinese people (PMID:16280386)
• glutathione S-transferase A1 (GSTA1) genotype as well as diet may have roles in development of breast cancer (PMID:16624829)
• results indicate that certain content in maotai liquor is able to induce GST A1 ARE transcriptional expression, which may provide protective effects for hepatic cells via an ERKs- and p38 K-dependent pathway (PMID:16786188)
• IL-1beta represses GSTA1 transcription via a mechanism involving overexpression of variant HNF-1C. (PMID:17021248)
• dinitrosyl-diglutathionyl-iron complex bound to Alpha class glutathione S-transferases with extraordinary high affinity in hepatocytes (PMID:17197702)
• GSTA1 polymorphisms is associated with dnan damage induced by tobacco smoke (PMID:17644396)
• Polymorphisms affecting GSTP1, GST alpha 1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in a population of white Spanish patients. (PMID:17716224)
• a possible use of ARNT2 and GST A1 as prognostic breast cancer biomarkers. (PMID:17899366)
• The aim of the present study is to investigate the influence of cytochromes P450 (CYP450) 1A1*2C and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to chronic myeloid leukaemia (CML). (PMID:18224491)
• The risk of hypertension was significantly increased in the GSTA1*B allele carriers having also the GSTM1 null genotype or both the GSTM1 and GSTT1 null genotypes. (PMID:18300949)
• Polymorphisms of glutathione S-transferase A1 and O1 and breast cancer among postmenopausal Danish women. (PMID:18414193)
• This is the first report to show that the GSTA1*B allele is a potential risk factor for smoking-related type 2 diabetes. (PMID:18430527)
• Keap1-dependent signaling pathway for the induction of the constitutive GST A1 expression during epithelial cell differentiati in Caco-2 cells. (PMID:18476723)
• Glutathione S-transferase A1 genetic variants reduce busulfan clearance in children undergoing hematopoietic cell transplantation. (PMID:18635758)
• Data show that GST-alpha expression is not seen in any cortex specimens from intractable epileptic patients and controls. (PMID:18644106)
• EdAG was identified as a metabolite of busulfan in a human liver cytosol and found to bind GSTA1-1 (PMID:18791061)
• Frequencies of polymorphic variants of RAD51, XRCC3, NQO1, GSTA1, GSTM1, GSTT1, CYP3A4 and XPD enzymes were similar in patients and controls. (PMID:19027952)
• Genotypic variants of CYBA rs4673 and GSTA1 rs3957357 were independent predictors of event free survival in diffuse large B-cell lymphoma treated with R-CHOP21 (PMID:19448608)
• Frequencies of normal alleles of GST genotypes were lower in patients with Down’s syndrome as compared to the controls. (PMID:19491810)

Cross-species orthologs

42 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstp1.1	ENSDARG00000103019
rattus_norvegicus	Gsta3l1	ENSRNOG00000024755
caenorhabditis_elegans		WBGENE00001749
caenorhabditis_elegans		WBGENE00001750
caenorhabditis_elegans		WBGENE00001751
caenorhabditis_elegans		WBGENE00001752
caenorhabditis_elegans		WBGENE00001753
caenorhabditis_elegans		WBGENE00001754
caenorhabditis_elegans		WBGENE00001755
caenorhabditis_elegans		WBGENE00001756
caenorhabditis_elegans		WBGENE00001757
caenorhabditis_elegans		WBGENE00001758
caenorhabditis_elegans		WBGENE00001759
caenorhabditis_elegans		WBGENE00001760
caenorhabditis_elegans		WBGENE00001761
caenorhabditis_elegans		WBGENE00001762
caenorhabditis_elegans		WBGENE00001764
caenorhabditis_elegans		WBGENE00001765
caenorhabditis_elegans		WBGENE00001766
caenorhabditis_elegans		WBGENE00001767
caenorhabditis_elegans		WBGENE00001769
caenorhabditis_elegans		WBGENE00001770
caenorhabditis_elegans		WBGENE00001771
caenorhabditis_elegans		WBGENE00001772
caenorhabditis_elegans	gst-25	WBGENE00001773
caenorhabditis_elegans		WBGENE00001774
caenorhabditis_elegans		WBGENE00001775
caenorhabditis_elegans		WBGENE00001776
caenorhabditis_elegans		WBGENE00001777
caenorhabditis_elegans		WBGENE00001779
caenorhabditis_elegans		WBGENE00001780
caenorhabditis_elegans		WBGENE00001781
caenorhabditis_elegans		WBGENE00001782
caenorhabditis_elegans		WBGENE00001783
caenorhabditis_elegans		WBGENE00001785
caenorhabditis_elegans		WBGENE00001786
caenorhabditis_elegans		WBGENE00001787
caenorhabditis_elegans		WBGENE00001789
caenorhabditis_elegans		WBGENE00018911
caenorhabditis_elegans		WBGENE00018912
caenorhabditis_elegans	W10C8.4	WBGENE00021127
caenorhabditis_elegans		WBGENE00021566

Paralogs (11): GSTP1 (ENSG00000084207), GSTM1 (ENSG00000134184), GSTM5 (ENSG00000134201), GSTM3 (ENSG00000134202), HPGDS (ENSG00000163106), GSTM4 (ENSG00000168765), GSTA4 (ENSG00000170899), GSTA3 (ENSG00000174156), GSTA5 (ENSG00000182793), GSTM2 (ENSG00000213366), GSTA2 (ENSG00000244067)

Protein

Protein identifiers

Glutathione S-transferase A1 — P08263 (reviewed: P08263)

Alternative names: 13-hydroperoxyoctadecadienoate peroxidase, Androst-5-ene-3,17-dione isomerase, GST HA subunit 1, GST class-alpha member 1, GST-epsilon, GSTA1-1, GTH1

All UniProt accessions (2): A0A140VJK4, P08263

UniProt curated annotations — full annotation on UniProt →

Function. Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid.

Subunit / interactions. Homodimer or heterodimer of GSTA1 and GSTA2.

Subcellular location. Cytoplasm.

Tissue specificity. Liver.

Activity regulation. The isomerase activity is inhibited by S-methylglutathione (GSMe).

Domain organisation. The C-terminal domain may form a component of the hydrophobic substrate-binding site, but in contrast appears not to be directly involved in GSH binding and is not absolutely essential for catalytic activity.

Similarity. Belongs to the GST superfamily. Alpha family.

RefSeq proteins (2): NP_001305988, NP_665683* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003080	GST_alpha	Family
IPR004045	Glutathione_S-Trfase_N	Domain
IPR004046	GST_C	Domain
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR050213	GST_superfamily	Family

Pfam: PF00043, PF02798

Enzyme classification (BRENDA):

• EC 2.5.1.18 — glutathione transferase (BRENDA: 178 organisms, 548 substrates, 680 inhibitors, 878 Km, 525 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
1-CHLORO-2,4-DINITROBENZENE	0.0003–223.6	289
GLUTATHIONE	0.0002–532.43	253
GSH	0.0003–37.4	62
REDUCED GLUTATHIONE	0.017–11.4	24
ETHACRYNIC ACID	0.0001–2.43	19
CUMENE HYDROPEROXIDE	0.038–14.3	10
(+)-2-BROMO-3-(4-NITROPHENYL)PROPANOIC ACID	0.023–0.417	8
MONOCHLOROBIMANE	0.004–0.25	8
4-CHLORO-7-NITROBENZO-2-OXA-1,3-DIAZOLE	0.324–3.866	7
1-IODOHEXANE	0.009–0.059	6
ALACHLOR	0.042–7.23	6
PHENETHYL ISOTHIOCYANATE	0.0065–0.14	6
STYRENE 7,8-OXIDE	0.064–0.365	6
1,2-DICHLORO-4-NITROBENZENE	0.27–1.4	5
1-CHLORO-2,3-DINITROBENZOATE	0.21–20.7	5

Catalyzed reactions (Rhea), 5 shown:

• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)
• androst-5-ene-3,17-dione = androst-4-ene-3,17-dione (RHEA:43936)
• (13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O (RHEA:48888)
• prostaglandin A2 + glutathione = prostaglandin A2-S-(R)-glutathione (RHEA:50796)
• prostaglandin J2 + glutathione = prostaglandin J2-S-(R)-glutathione (RHEA:50804)

UniProt features (42 total): helix 12, sequence conflict 5, strand 5, binding site 4, modified residue 3, sequence variant 3, mutagenesis site 3, chain 2, turn 2, domain 2, initiator methionine 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ATR	X-RAY DIFFRACTION	1.29
1K3Y	X-RAY DIFFRACTION	1.3
1K3L	X-RAY DIFFRACTION	1.5
6ATO	X-RAY DIFFRACTION	1.55
8BHC	X-RAY DIFFRACTION	1.56
5LD0	X-RAY DIFFRACTION	1.6
6ATP	X-RAY DIFFRACTION	1.7
1PL1	X-RAY DIFFRACTION	1.75
3KTL	X-RAY DIFFRACTION	1.75
3Q74	X-RAY DIFFRACTION	1.79
1K3O	X-RAY DIFFRACTION	1.8
1PL2	X-RAY DIFFRACTION	1.8
2R3X	X-RAY DIFFRACTION	1.8
1XWG	X-RAY DIFFRACTION	1.85
1LBK	X-RAY DIFFRACTION	1.86
3ZFB	X-RAY DIFFRACTION	1.86
8BHE	X-RAY DIFFRACTION	1.87
3ZFL	X-RAY DIFFRACTION	1.88
5JCU	X-RAY DIFFRACTION	1.93
1YDK	X-RAY DIFFRACTION	1.95
3I6A	X-RAY DIFFRACTION	1.98
1GSE	X-RAY DIFFRACTION	2
1PKW	X-RAY DIFFRACTION	2
6ATQ	X-RAY DIFFRACTION	2
7BIB	X-RAY DIFFRACTION	2.03
1USB	X-RAY DIFFRACTION	2.07
1PKZ	X-RAY DIFFRACTION	2.1
4HJ2	X-RAY DIFFRACTION	2.1
3L0H	X-RAY DIFFRACTION	2.13
6YAW	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08263-F1	97.57	0.99

Functional residue map

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

Ligand- & substrate-binding residues (4): 9; 45; 54–55; 67–68

Post-translational modifications (3): 2, 4, 1

Mutagenesis-validated functional residues (3):

Position	Phenotype
9	decreased isomerase activity.
71	no significant effect on enzyme activity. reduces protein stability.
216	confers ability to hydrolyze s-glutathionyl benzoate to glutathione and benzoic acid.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-189483	Heme degradation
R-HSA-9748787	Azathioprine ADME
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 151 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, REACTOME_METABOLISM_OF_PORPHYRINS, GOZGIT_ESR1_TARGETS_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, chr6p12

GO Biological Process (8): prostaglandin metabolic process (GO:0006693), glutathione metabolic process (GO:0006749), xenobiotic metabolic process (GO:0006805), epithelial cell differentiation (GO:0030855), linoleic acid metabolic process (GO:0043651), glutathione derivative biosynthetic process (GO:1901687), lipid metabolic process (GO:0006629), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (9): glutathione transferase activity (GO:0004364), glutathione peroxidase activity (GO:0004602), steroid Delta-isomerase activity (GO:0004769), fatty acid binding (GO:0005504), peroxidase activity (GO:0004601), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), transferase activity (GO:0016740), isomerase activity (GO:0016853)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Metabolism of porphyrins	1
Drug ADME	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
cellular anatomical structure	2
prostanoid metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
cell differentiation	1
epithelium development	1
long-chain fatty acid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
sulfur compound biosynthetic process	1
primary metabolic process	1
cellular detoxification	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
peroxidase activity	1
intramolecular oxidoreductase activity, transposing C=C bonds	1
lipid binding	1
monocarboxylic acid binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
binding	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTA1	SLCO6A1	Q86UG4	906
GSTA1	UGT1A6	P19224	753
GSTA1	UGT1A8	Q9HAW9	738
GSTA1	UGT1A1	P22309	736
GSTA1	UGT1A7	Q9HAW7	734
GSTA1	UGT1A10	Q9HAW8	734
GSTA1	UGT1A4	P22310	732
GSTA1	CILK1	Q9UPZ9	714
GSTA1	NQO1	P15559	701
GSTA1	GSTO1	P78417	666
GSTA1	GCLC	P48506	665
GSTA1	EPHX1	P07099	661
GSTA1	GPX3	P22352	632
GSTA1	GSTT2B	P0CG30	631
GSTA1	GSTO2	Q9H4Y5	622

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GSTA2	GSTA4	psi-mi:“MI:0914”(association)	0.920
GGTLC1	GSTA1	psi-mi:“MI:0915”(physical association)	0.590
GSTA1	GSTA4	psi-mi:“MI:0914”(association)	0.530
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.530
PPP2CB	GSTA1	psi-mi:“MI:0915”(physical association)	0.370
GSTA1	ST3GAL1	psi-mi:“MI:0915”(physical association)	0.370
YWHAE	GSTA1	psi-mi:“MI:0915”(physical association)	0.370
LSM3	GSTA1	psi-mi:“MI:0915”(physical association)	0.370
GSTA1	RPAIN	psi-mi:“MI:0915”(physical association)	0.370
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.350
GSTA5	EIF3F	psi-mi:“MI:0914”(association)	0.350
SSX2	GSTA1	psi-mi:“MI:0914”(association)	0.350
TMEM68	GSTA1	psi-mi:“MI:0914”(association)	0.350
USP51	GSTA1	psi-mi:“MI:0914”(association)	0.350
GSTA1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): GSTA3 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), GSTA3 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), GSTA1 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), GSTA1 (Affinity Capture-MS), GSTA1 (Co-purification), GSTA1 (Affinity Capture-MS), GSTA3 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1U8QXK4, A0A1U9YI21, B5BP46, C8VQ63, F4IA73, O15217, O74830, P08263, P09210, P30102, P32111, P34277, P34345, P42936, P43387, P46417, P46421, P46429, P49332, P50471, Q00717, Q2UPB2, Q4WB03, Q54VI4, Q55FF3, Q5E9G0, Q5M883, Q6AXY0, Q6NLB0, Q6NMS0, Q6Q882, Q7RTV2, Q86AU1, Q9CA57, Q9CAS6, Q9FUS6, Q9FUS9, Q9FUT0, Q9FUT1, Q9LQ48

Diamond homologs: O15217, O18879, O73888, P00502, P04903, P04904, P04906, P08263, P09210, P09211, P10648, P13745, P14942, P19157, P24472, P26624, P26697, P30115, P35661, P46088, P46418, P46424, P46425, P47954, P51781, P80031, P80894, P81706, P81942, Q08392, Q08393, Q08862, Q08863, Q16772, Q28035, Q28514, Q54YN2, Q556G3, Q5E9G0, Q5R8R5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NFE2L2	“down-regulates quantity by repression”	GSTA1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	GSTA1	“transcriptional regulation”
GSTA1	up-regulates	Proliferation
GSTA1	down-regulates	Apoptosis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

638 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52792983:AAGAC:A	acceptor_gain	1.0000
6:52792984:AGAC:A	acceptor_gain	1.0000
6:52792986:AC:A	acceptor_gain	1.0000
6:52792987:CC:C	acceptor_gain	1.0000
6:52792988:C:CC	acceptor_gain	1.0000
6:52792988:C:CG	acceptor_loss	1.0000
6:52792989:T:C	acceptor_loss	1.0000
6:52794120:CTTA:C	donor_gain	1.0000
6:52794121:TTA:T	donor_loss	1.0000
6:52794122:TA:T	donor_loss	1.0000
6:52794123:A:AC	donor_gain	1.0000
6:52794124:C:CA	donor_gain	1.0000
6:52794124:CT:C	donor_gain	1.0000
6:52794124:CTT:C	donor_gain	1.0000
6:52794124:CTTT:C	donor_gain	1.0000
6:52794124:CTTTT:C	donor_gain	1.0000
6:52794262:CAATC:C	acceptor_gain	1.0000
6:52794263:AATC:A	acceptor_gain	1.0000
6:52794264:ATC:A	acceptor_gain	1.0000
6:52794265:TC:T	acceptor_gain	1.0000
6:52794265:TCCTG:T	acceptor_loss	1.0000
6:52794266:CC:C	acceptor_gain	1.0000
6:52794266:CCTG:C	acceptor_loss	1.0000
6:52794267:C:CC	acceptor_gain	1.0000
6:52796180:A:AC	donor_gain	1.0000
6:52796181:C:CC	donor_gain	1.0000
6:52796181:CAGGG:C	donor_gain	1.0000
6:52796191:T:A	donor_gain	1.0000
6:52796204:T:A	donor_gain	1.0000
6:52796314:TCT:T	acceptor_loss	1.0000

AlphaMissense

1474 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52791936:A:C	F197L	0.989
6:52791936:A:T	F197L	0.989
6:52791938:A:G	F197L	0.989
6:52797635:A:C	F30L	0.989
6:52797635:A:T	F30L	0.989
6:52797637:A:G	F30L	0.989
6:52796298:G:C	F52L	0.988
6:52796298:G:T	F52L	0.988
6:52796300:A:G	F52L	0.988
6:52799207:A:G	W21R	0.988
6:52799207:A:T	W21R	0.988
6:52792940:G:C	S154R	0.975
6:52792940:G:T	S154R	0.975
6:52792942:T:G	S154R	0.975
6:52796253:C:A	Q67H	0.974
6:52796253:C:G	Q67H	0.974
6:52796281:A:T	V58D	0.974
6:52792923:A:G	L160P	0.971
6:52799209:C:G	R20P	0.971
6:52799219:C:T	E17K	0.969
6:52794247:C:G	G98R	0.967
6:52791915:C:A	R204S	0.966
6:52791915:C:G	R204S	0.966
6:52799203:A:G	L22P	0.966
6:52799243:A:G	Y9H	0.963
6:52796227:G:T	A76D	0.961
6:52796300:A:T	F52I	0.961
6:52799228:C:G	G14R	0.960
6:52792933:C:G	D157H	0.959
6:52791937:A:G	F197S	0.958

dbSNP variants (sampled 300 via entrez): RS1000736745 (6:52797560 C>G,T), RS1000768383 (6:52797833 A>T), RS1000916103 (6:52802563 C>T), RS1000997845 (6:52792807 C>G,T), RS1001348549 (6:52792445 A>C), RS1001402223 (6:52799868 C>G,T), RS1001436368 (6:52800159 A>G), RS1001663724 (6:52794938 CTT>C), RS1002185317 (6:52803664 G>C,T), RS1002409943 (6:52798999 C>T), RS1002441091 (6:52799203 A>G), RS1002685152 (6:52803383 C>T), RS1003072429 (6:52801078 A>G), RS1003103768 (6:52801338 A>G,T), RS1003926827 (6:52798524 T>C)

Disease associations

OMIM: gene MIM:138359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004603_27	Platelet count	3.000000e-14
GCST004607_143	Plateletcrit	4.000000e-16
GCST010083_310	Hemoglobin levels	1.000000e-20
GCST011345_7	Triglyceride levels	1.000000e-09
GCST90002383_451	Hematocrit	3.000000e-22
GCST90002384_62	Hemoglobin	6.000000e-26
GCST90002400_586	Plateletcrit	5.000000e-29
GCST90002402_700	Platelet count	1.000000e-25
GCST90011900_187	Serum alkaline phosphatase levels	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004509	hemoglobin measurement
EFO:0004530	triglyceride measurement
EFO:0004348	hematocrit
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3409 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,004 (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
CHEMBL456	ETHACRYNIC ACID	4	20,004

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3957356	Efficacy	3	cyclophosphamide	Lupus Nephritis
rs3957357	Efficacy	3	doxorubicin	Sarcoma
rs3957357	Metabolism/PK	3	busulfan	Transplantation
rs3957357	Toxicity	3	cisplatin;cyclophosphamide	Anemia;Ovarian Neoplasms
rs3957357	Efficacy	3	cyclophosphamide;doxorubicin;prednisone;rituximab;vincristine	Lymphoma;Large B-Cell;Diffuse

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3957356	GSTA1	3	2.25	1	cyclophosphamide
rs3957357	GSTA1, GSTA6P	3	1.75	4	cisplatin;cyclophosphamide;doxorubicin;cyclophosphamide;doxorubicin;prednisone;rituximab;vincristine;busulfan
rs1051775	GSTA1		0.00	0

Binding affinities (BindingDB)

107 measured of 107 human assays (107 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-benzyl-N-[2-(dimethylamino)ethyl]-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	0.6 nM	US-9296757: Substituted benzothienopyrimidines
N,N-bis(2-methoxyethyl)-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	0.7 nM	US-9296757: Substituted benzothienopyrimidines
N-butyl-N-(cyanomethyl)-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	1 nM	US-9296757: Substituted benzothienopyrimidines
N-ethyl-N-(2-methoxyethyl)-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	1 nM	US-9296757: Substituted benzothienopyrimidines
N-butyl-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-methyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	1.9 nM	US-9296757: Substituted benzothienopyrimidines
N-(2-methoxyethyl)-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	2 nM	US-9296757: Substituted benzothienopyrimidines
N-ethyl-4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propan-2-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	3 nM	US-9296757: Substituted benzothienopyrimidines
4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propan-2-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	4 nM	US-9296757: Substituted benzothienopyrimidines
4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N,N-dimethyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	4 nM	US-9296757: Substituted benzothienopyrimidines
N-benzyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	9 nM	US-9296757: Substituted benzothienopyrimidines
N-benzyl-N-[2-(dimethylamino)ethyl]-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	9 nM	US-9296757: Substituted benzothienopyrimidines
N-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]-N’,N’-dimethylethane-1,2-diamine	IC50	11 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-[[3-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	11 nM	US-9296757: Substituted benzothienopyrimidines
1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]azetidin-3-ol	IC50	12 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
[1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]piperidin-3-yl]methanol	IC50	13 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
[(3R)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-yl]methanol	IC50	14 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
(3R)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]piperidin-3-ol	IC50	15 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
(3S)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol	IC50	15 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
(3R)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol	IC50	15 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
ethyl 4-[(5-methoxy-2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxylate	IC50	15 nM	US-9296757: Substituted benzothienopyrimidines
1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol	IC50	17 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
3-(1-benzofuran-2-yl)-N-(2-pyridin-2-ylethyl)imidazo[1,2-b]pyridazin-6-amine	IC50	17 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
[(2S)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-2-yl]methanol	IC50	19 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
N-(2-methoxyethyl)-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	19 nM	US-9296757: Substituted benzothienopyrimidines
[(3S)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-yl]methanol	IC50	20 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
N-butyl-N-(cyanomethyl)-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	20 nM	US-9296757: Substituted benzothienopyrimidines
N-butyl-N-methyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	21 nM	US-9296757: Substituted benzothienopyrimidines
[(2R)-1-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-2-yl]methanol	IC50	22 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
3-(1-benzofuran-2-yl)-N-(pyridin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-amine	IC50	23 nM	US-9284319: Heterocyclyl aminoimidazopyridazines
N-ethyl-N-(2-methoxyethyl)-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	24 nM	US-9296757: Substituted benzothienopyrimidines
N-[(3-fluorophenyl)methyl]-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	25 nM	US-9296757: Substituted benzothienopyrimidines
N-methyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-(oxolan-2-ylmethyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	27 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine-2-carbonyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	27 nM	US-9296757: Substituted benzothienopyrimidines
N-(2-hydroxyethyl)-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propan-2-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	28 nM	US-9296757: Substituted benzothienopyrimidines
N,N-bis(2-methoxyethyl)-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	30 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-(3-methoxypiperidine-1-carbonyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	30 nM	US-9296757: Substituted benzothienopyrimidines
N-methyl-N-[1-[4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	32 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-(2,6-dimethylmorpholine-4-carbonyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	32 nM	US-9296757: Substituted benzothienopyrimidines
1-[4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carbonyl]piperidine-3-carbonitrile	IC50	32 nM	US-9296757: Substituted benzothienopyrimidines
4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-phenyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	33 nM	US-9296757: Substituted benzothienopyrimidines
N-(4-hydroxybutyl)-N-methyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	34 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-[3-(dimethylamino)pyrrolidine-1-carbonyl]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	34 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-[4-(cyclopropylmethyl)piperazine-1-carbonyl]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	34 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-[3-(2-hydroxyethyl)-4-methylpiperazine-1-carbonyl]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	34 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-[2-(hydroxymethyl)pyrrolidine-1-carbonyl]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	35 nM	US-9296757: Substituted benzothienopyrimidines
4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-N-propan-2-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	36 nM	US-9296757: Substituted benzothienopyrimidines
N-[2-(dimethylamino)ethyl]-N-methyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	36 nM	US-9296757: Substituted benzothienopyrimidines
6-[[7-(4-ethylpiperazine-1-carbonyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]amino]-3H-1,3-benzothiazol-2-one	IC50	36 nM	US-9296757: Substituted benzothienopyrimidines
2-methyl-N-[[4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-7-yl]methyl]propanamide	IC50	37 nM	US-9296757: Substituted benzothienopyrimidines
N-(2-cyanoethyl)-N-ethyl-4-[(2-oxo-3H-1,3-benzothiazol-6-yl)amino]-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine-7-carboxamide	IC50	38 nM	US-9296757: Substituted benzothienopyrimidines

ChEMBL bioactivities

38 potent at pChembl≥5 of 46 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.86	IC50	13.7	nM	CHEMBL211727
7.84	IC50	14.3	nM	CHEMBL211916
7.62	IC50	24	nM	CHEMBL212685
7.49	IC50	32.7	nM	CHEMBL212097
7.41	IC50	39.3	nM	CHEMBL209755
7.28	IC50	52.1	nM	CHEMBL379437
7.00	IC50	98.9	nM	CHEMBL216505
6.89	IC50	130	nM	CHEMBL5169380
6.89	IC50	130	nM	CHEMBL5178537
6.80	IC50	160	nM	CHEMBL5178537
6.75	IC50	180	nM	CHEMBL3310889
6.75	IC50	180	nM	CHEMBL3310888
6.75	IC50	180	nM	CHEMBL3310886
6.75	IC50	180	nM	CHEMBL3310887
6.75	IC50	180	nM	CHEMBL5289853
6.62	IC50	240	nM	CHEMBL3310888
6.55	IC50	280	nM	CHEMBL5169380
6.48	IC50	330	nM	CHEMBL3310887
6.47	IC50	340	nM	CHEMBL5174343
6.44	Ki	360	nM	CHEMBL3310888
6.42	Ki	380	nM	CHEMBL3310887
6.37	IC50	430	nM	CHEMBL5199600
6.08	Ki	840	nM	CHEMBL58135
5.86	IC50	1370	nM	CHEMBL5184218
5.83	Ki	1470	nM	CHEMBL3310886
5.77	Ki	1700	nM	CHEMBL558948
5.77	Ki	1700	nM	CHEMBL556598
5.77	Ki	1700	nM	CHEMBL557211
5.76	Ki	1750	nM	CHEMBL3310889
5.75	IC50	1770	nM	CHEMBL3310886
5.73	IC50	1870	nM	CHEMBL5203780
5.54	IC50	2910	nM	CHEMBL5203780
5.30	IC50	5000	nM	ETHACRYNIC ACID
5.28	IC50	5200	nM	CHEMBL5184218
5.24	Ki	5800	nM	CHEMBL58507
5.09	Ki	8100	nM	CHEMBL558948
5.09	Ki	8100	nM	CHEMBL556598
5.09	Ki	8100	nM	CHEMBL557211

PubChem BioAssay actives

38 with measured affinity, of 140 total; 24 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
3-[[3-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]propanoylamino]methyl]-5-[[3-[[2-[2,3-dichloro-4-(2-methylprop-2-enoyl)phenoxy]acetyl]amino]propanoylamino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0137	uM
3-[[4-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]butanoylamino]methyl]-5-[[4-[[2-[2,3-dichloro-4-(2-methylprop-2-enoyl)phenoxy]acetyl]amino]butanoylamino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0143	uM
3,5-bis[[[2-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]acetyl]amino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0240	uM
3,5-bis[[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0327	uM
3-[[6-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]hexanoylamino]methyl]-5-[[6-[[2-[2,3-dichloro-4-(2-methylprop-2-enoyl)phenoxy]acetyl]amino]hexanoylamino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0393	uM
3-[[8-[[2-[2,3-dichloro-4-(1-hydroxy-2-methylidenebutyl)phenoxy]acetyl]amino]octanoylamino]methyl]-5-[[9-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]nonanoylamino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0521	uM
3-[[4-[4-[4-[[2-(4-but-1-en-2-yl-2,3-dichlorophenoxy)acetyl]amino]butanoylamino]butanoylamino]butanoylamino]methyl]-5-[[4-[4-[4-[[2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetyl]amino]butanoylamino]butanoylamino]butanoylamino]methyl]benzamide	266616: Inhibition of GST A1-1	ic50	0.0989	uM
(26,28-dihydroxy-25,27-dioctoxy-17-phosphonocarbonylpentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaene-5-carbonyl)phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	0.1300	uM
(25,27-didodecoxy-26,28-dihydroxy-17-phosphonocarbonylpentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaene-5-carbonyl)phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	0.1300	uM
(2-hydroxyphenyl)-(2-hydroxy-5-phenylphenyl)methanone	1956800: Inhibition of recombinant human GSTA1-1	ic50	0.1800	uM
(5-bromo-2-hydroxyphenyl)-(2-hydroxyphenyl)methanone	1956800: Inhibition of recombinant human GSTA1-1	ic50	0.1800	uM
N-[bis(2-hydroxyphenyl)methylideneamino]benzamide	1956800: Inhibition of recombinant human GSTA1-1	ic50	0.1800	uM
N-[(Z)-[(5-bromo-2-hydroxyphenyl)-(2-hydroxyphenyl)methylidene]amino]acetamide	1182536: Inhibition of human GSTA1 activity assessed as conjugation between CDNB and GSH	ic50	0.1800	uM
N-[(E)-[(5-bromo-2-hydroxyphenyl)-(2-hydroxyphenyl)methylidene]amino]acetamide	1956800: Inhibition of recombinant human GSTA1-1	ic50	0.1800	uM
(25,27-dibutoxy-26,28-dihydroxy-17-phosphonocarbonylpentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaene-5-carbonyl)phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	0.3400	uM
(26,28-dihydroxy-17-phosphonocarbonyl-25,27-dipropoxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaene-5-carbonyl)phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	0.4300	uM
2-amino-5-[[1-(carboxymethylamino)-3-hexylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75272: Inhibitory activity was measured on recombinant human Glutathione-S-transferase A1 enzyme	ki	0.8400	uM
[26,28-dihydroxy-17-[hydroxy(diphosphono)methyl]-25,27-dipropoxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaene-5-carbonyl]phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	1.3700	uM
(4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-(benzenesulfonamido)-5-oxopentanoic acid	428441: Inhibition of human GSTA1-1 expressed in Escherichia coli BL21 (DE3) by 1-chloro-2,4-dinitrobenzene competitive assay	ki	1.7000	uM
(4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-(benzenesulfonamido)-5-oxopentanoic acid	428441: Inhibition of human GSTA1-1 expressed in Escherichia coli BL21 (DE3) by 1-chloro-2,4-dinitrobenzene competitive assay	ki	1.7000	uM
(4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-4-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-(benzenesulfonamido)-5-oxopentanoic acid	428441: Inhibition of human GSTA1-1 expressed in Escherichia coli BL21 (DE3) by 1-chloro-2,4-dinitrobenzene competitive assay	ki	1.7000	uM
(26,28-dihydroxy-25,27-dipropoxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaene-5-carbonyl)phosphonic acid	1896235: Inhibition of recombinant human GSTA1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis	ic50	1.8700	uM
Ethacrynic Acid	266616: Inhibition of GST A1-1	ic50	5.0000	uM
2-amino-5-[[1-[[carboxy(phenyl)methyl]amino]-3-hexylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75272: Inhibitory activity was measured on recombinant human Glutathione-S-transferase A1 enzyme	ki	5.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Glutathione	affects binding, decreases abundance, decreases reaction, affects cotreatment, affects metabolic processing (+1 more)	11
Busulfan	affects abundance, affects metabolic processing, affects response to substance, affects cotreatment, decreases response to substance	8
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	5
Cyclosporine	affects cotreatment, affects expression, decreases expression	5
sulforaphane	decreases reaction, increases expression, decreases expression	4
dibenzo(a,l)pyrene	decreases expression, increases expression, affects cotreatment, affects metabolic processing, decreases activity (+2 more)	4
Acetaminophen	decreases expression, increases secretion, increases expression, affects cotreatment, increases reaction (+1 more)	4
Dinitrochlorobenzene	increases metabolic processing, affects cotreatment, affects metabolic processing, affects binding	4
Phenobarbital	decreases expression, decreases reaction, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases response to substance	4
Aflatoxin B1	affects expression, affects binding, decreases expression	4
2-(acetoxyamino)-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects metabolic processing, decreases activity, increases response to substance	3
Quercetin	affects cotreatment, decreases expression, increases expression	3
Rifampin	decreases reaction, increases expression, affects cotreatment	3
5-androstene-3,17-dione	affects metabolic processing, increases metabolic processing	2
bisphenol A	increases response to substance, affects expression, increases expression	2
oltipraz	decreases expression, decreases reaction, increases secretion	2
hexylglutathione	affects binding	2
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	2
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression, affects response to substance, affects cotreatment, increases expression	2
N-acetylsphingosine	decreases expression, increases reaction, increases secretion	2
Arsenic Trioxide	increases expression, increases reaction	2
Ascorbic Acid	affects binding, affects cotreatment, increases expression, decreases expression	2
Butyrates	increases expression	2
Cadmium	increases expression, increases response to substance, decreases expression, increases abundance	2
Chenodeoxycholic Acid	affects cotreatment, decreases expression	2
Chlorambucil	decreases response to substance, increases reaction, decreases activity, affects cotreatment, affects metabolic processing	2
Cisplatin	affects cotreatment, affects expression, decreases response to substance	2
Coffee	increases expression, affects response to substance, affects reaction	2

ChEMBL screening assays

44 unique, capped per target: 31 binding, 13 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1033244	Binding	Specific activity of human recombinant Glutathione S-transferase A1 at 50 uM by spectrophotometric analysis in presence of glutathione	Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs. — Bioorg Med Chem
CHEMBL1743222	ADMET	Substrates for human cytosolic glutathione transferase GSTA1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Clinical trials (associated diseases)

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