GSTM1

Summary

GSTM1 (glutathione S-transferase mu 1, HGNC:4632) is a protein-coding gene on chromosome 1p13.3, encoding Glutathione S-transferase Mu 1 (P09488). Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene.

Source: NCBI Gene 2944 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 37 total
• Druggable target: yes
• MANE Select transcript: NM_000561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4632
Approved symbol	GSTM1
Name	glutathione S-transferase mu 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MU, H-B
Ensembl gene	ENSG00000134184
Ensembl biotype	protein_coding
OMIM	138350
Entrez	2944

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000309851, ENST00000349334, ENST00000369819, ENST00000369823, ENST00000476065, ENST00000483399, ENST00000490021, ENST00000490171, ENST00000876522, ENST00000876523, ENST00000876524, ENST00000876525, ENST00000876526, ENST00000876527

RefSeq mRNA: 2 — MANE Select: NM_000561 NM_000561, NM_146421

CCDS: CCDS809, CCDS810

Canonical transcript exons

ENST00000309851 — 8 exons

Exon	Start	End
ENSE00001715778	109690271	109690366
ENSE00001716973	109690454	109690564
ENSE00001753103	109688170	109688245
ENSE00001825142	109693206	109693745
ENSE00002579583	109687817	109687909
ENSE00003484138	109689225	109689325
ENSE00003512826	109689048	109689129
ENSE00003588409	109688673	109688737

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9024 / max 891.0039, expressed in 920 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4445	11.0030	893
4446	6.8994	878

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
smooth muscle tissue	UBERON:0001135	96.40	gold quality
mucosa of stomach	UBERON:0001199	94.18	gold quality
mucosa of transverse colon	UBERON:0004991	93.96	gold quality
apex of heart	UBERON:0002098	91.17	gold quality
left uterine tube	UBERON:0001303	87.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.19	gold quality
duodenum	UBERON:0002114	83.30	gold quality
adenohypophysis	UBERON:0002196	83.20	gold quality
right lobe of liver	UBERON:0001114	83.16	gold quality
right ovary	UBERON:0002118	82.87	gold quality
liver	UBERON:0002107	82.41	gold quality
endocervix	UBERON:0000458	80.73	gold quality
left adrenal gland cortex	UBERON:0035825	80.06	gold quality
ovary	UBERON:0000992	79.79	gold quality
myometrium	UBERON:0001296	79.50	gold quality
muscle tissue	UBERON:0002385	79.50	gold quality
thoracic mammary gland	UBERON:0005200	79.40	gold quality
metanephros cortex	UBERON:0010533	79.01	gold quality
left ovary	UBERON:0002119	78.59	gold quality
uterine cervix	UBERON:0000002	78.26	gold quality
esophagus mucosa	UBERON:0002469	78.19	gold quality
skeletal muscle tissue	UBERON:0001134	78.07	gold quality
left adrenal gland	UBERON:0001234	78.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.78	gold quality
ascending aorta	UBERON:0001496	77.57	gold quality
gastrocnemius	UBERON:0001388	77.35	gold quality
esophagus	UBERON:0001043	77.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.05	gold quality
muscle of leg	UBERON:0001383	77.01	gold quality
superior frontal gyrus	UBERON:0002661	76.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	923.76
E-MTAB-6911	no	53.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ETS1, HMGA1, MYB, PARP1, PAX5, SPI1, TBP

miRNA regulators (miRDB)

30 targeting GSTM1, 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-6876-5P	100.00	67.68	2126
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-4278	95.28	65.49	351
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 33)

• GSTM1 activity might be related to the metabolism of 1-hydroxypyrene and 2-naphthol. (PMID:11641039)
• polymorphisms associated with idiopathic Parkinson’s disease (PMID:11688992)
• different genotype combinations of p53 and GSTM1 increase the risk of developing specific histological subtypes of NSCLC. (PMID:11751390)
• patients with carcinoma of the breast and inheritance of a combined gene deletion of GSTM1 and GSTT1 might bear an increased risk to develop a secondary therapy-induced hematologic neoplasia (PMID:11792413)
• Loss of glutathione s-transferase mu phenotype is associated with colorectal adenocarcinoma (PMID:11809532)
• the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTM1 genotype (PMID:11815259)
• Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes (PMID:11844594)
• Glutathione-S-transferase M1 genotype in patients with hepatocellular carcinoma (PMID:11859714)
• Polymorphisms of glutathione S-transferase M1 and male infertility in Taiwanese patients with varicocele (PMID:11870126)
• we investigated the relationship between the levels of aromatic DNA adducts in breast tissues and polymorphisms of the drug-metabolizing genes CYP1A1, NAT2, and GSTM1 in 166 women having breast cancer (PMID:11872636)
• Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. (PMID:11920399)
• GSTM1 genotype may modulate association between urinary 1-hydroxypyrene and glycophorin a mutation in workers exposed to PAHs; should be controlled for in environmental exposure studies (PMID:11936216)
• Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. GSTm enzyme positivity rate of the lung cancer patient group (39%) was significantly lower than the control group. (PMID:11939169)
• polymorphism related to chronic lymphocytic leukemia (PMID:12010828)
• polymorphism of and susceptibility to oral cancer in an Indian population (PMID:12016153)
• effect of genotype on sister chromatid exchange induction by styrene in cultured human lymphocytes (PMID:12016165)
• Childhood acute lymphoblastic leukemia was not associated with the GSTM1-null genotype or the double-null genotype in blacks or whites, in contrast to previous reports. (PMID:12070010)
• association beeteen polymorphism and survival in colorectal cancer (PMID:12072547)
• association of colorectal cancer with meat consumption modified by GSTM1 genotype (PMID:12074508)
• Polymorphisms that determine the activity of glutathione transferase GSTM1 appear to significantly influence cutaneous inflammatory reactions after exposure to UV light. (PMID:12083949)
• protective effect mediated by the presence of GSTM1 genes in pediatric non-Hodgkin’s lymphoma. (PMID:12091121)
• There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction. (PMID:12117698)
• Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals (PMID:12139976)
• An association between GSTM1 genotypes and ALL-L1 susceptibility was found in northern Portuguese children. Full loss of GSTM1 activity is an ALL risk factor but having one functional allele confers some protection. (PMID:12145701)
• certain null GST genotypes may be associated with an elevated risk of breast cancer and the association may be modified by charred meat intake and cigarette smoking (PMID:12150456)
• effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk (PMID:12151353)
• The deficient genotypes for GSTM1 and GSTP1 seem thus to be important risk modifiers for lung cancer, especially in combination. (PMID:12189190)
• In two workers accidently exposed to styrene the relative proportions of diastereoisomers of mercapturic acid were influenced by GSTM1 polymorphism. (PMID:12191879)
• Relationship between GSTM1 polymorphism and susceptibility to colon cancer (PMID:12210502)
• Women with a GSTM1-null genotype may have an increased risk of breast cancer. (PMID:12296511)
• analysis of GSTM1 polymorphisms in Bronchial asthma patients and healthy people in Russia (PMID:12325261)
• Deletions have a negative prognostic value in adult acute myeloid leukemia (PMID:12351375)
• association between carcinogen-DNA damage, enzyme genotypes and risk of lung cancer (PMID:12376472)

Cross-species orthologs

48 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstp1.1	ENSDARG00000103019
mus_musculus	Gstm3	ENSMUSG00000004038
mus_musculus	Gstm2	ENSMUSG00000040562
mus_musculus	Gstm1	ENSMUSG00000058135
mus_musculus	Gstm6	ENSMUSG00000068762
rattus_norvegicus	Gstm1	ENSRNOG00000029726
rattus_norvegicus	Gstm5l	ENSRNOG00000060939
rattus_norvegicus		ENSRNOG00000071330
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), GSTM5 (ENSG00000134201), GSTM3 (ENSG00000134202), HPGDS (ENSG00000163106), GSTM4 (ENSG00000168765), GSTA4 (ENSG00000170899), GSTA3 (ENSG00000174156), GSTA5 (ENSG00000182793), GSTM2 (ENSG00000213366), GSTA1 (ENSG00000243955), GSTA2 (ENSG00000244067)

Protein

Protein identifiers

Glutathione S-transferase Mu 1 — P09488 (reviewed: P09488)

Alternative names: GST HB subunit 4, GST class-mu 1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4

All UniProt accessions (7): B9ZVX7, E7EWW9, P09488, H3BQT3, H3BRM6, X5D932, X5DR03

UniProt curated annotations — full annotation on UniProt →

Function. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). Participates in the formation of novel hepoxilin regioisomers.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Liver (at protein level).

Polymorphism. There are two alleles; GSTM1A and GSTM1B which differ in position 173. The sequence shown is that of allele GSTM1A.

Similarity. Belongs to the GST superfamily. Mu family.

Isoforms (2)

UniProt ID	Names	Canonical?
P09488-1	1	yes
P09488-2	2

RefSeq proteins (2): NP_000552, NP_666533 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003081	GST_mu	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), 6 shown:

• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)
• 11(S)-hydroxy-14(S),15(S)-epoxy-(5Z,8Z,12E)-eicosatrienoate + glutathione = (11S,15S)-dihydroxy-14(R)-S-glutathionyl-(5Z,8Z,12E)-eicosatrienoate (RHEA:50260)
• prostaglandin A2 + glutathione = prostaglandin A2-S-(R)-glutathione (RHEA:50796)
• prostaglandin A2 + glutathione = prostaglandin A2-S-(S)-glutathione (RHEA:50800)
• prostaglandin J2 + glutathione = prostaglandin J2-S-(R)-glutathione (RHEA:50804)
• prostaglandin J2 + glutathione = prostaglandin J2-S-(S)-glutathione (RHEA:50808)

UniProt features (42 total): helix 9, strand 7, mutagenesis site 6, binding site 6, turn 3, modified residue 2, sequence variant 2, domain 2, sequence conflict 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7BEU	X-RAY DIFFRACTION	1.59
1XW6	X-RAY DIFFRACTION	1.9
1XWK	X-RAY DIFFRACTION	2.3
1YJ6	X-RAY DIFFRACTION	2.5
8VOU	X-RAY DIFFRACTION	2.55
1GTU	X-RAY DIFFRACTION	2.68
2F3M	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09488-F1	98.29	1.00

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 (6): 7–8; 43–46; 50; 59–60; 72–73; 116

Post-translational modifications (2): 34, 210

Mutagenesis-validated functional residues (6):

Position	Phenotype
7	reduces catalytic activity 100-fold.
108	reduces catalytic activity by half.
108	changes the properties of the enzyme toward some substrates.
109	reduces catalytic activity by half.
116	reduces catalytic activity 10-fold.
116	slight increase of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-9748787	Azathioprine ADME
R-HSA-9753281	Paracetamol ADME

MSigDB gene sets: 215 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, MODULE_255, GNF2_GSTM1, GNF2_HPN, MODULE_317, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, MODULE_66, MODULE_118, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS

GO Biological Process (8): prostaglandin metabolic process (GO:0006693), glutathione metabolic process (GO:0006749), nitrobenzene metabolic process (GO:0018916), xenobiotic catabolic process (GO:0042178), hepoxilin biosynthetic process (GO:0051122), cellular detoxification of nitrogen compound (GO:0070458), glutathione derivative biosynthetic process (GO:1901687), lipid metabolic process (GO:0006629)

GO Molecular Function (6): glutathione transferase activity (GO:0004364), enzyme binding (GO:0019899), protein homodimerization activity (GO:0042803), glutathione binding (GO:0043295), transferase activity (GO:0016740), identical protein binding (GO:0042802)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Drug ADME	2
Phase II - Conjugation of compounds	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
prostanoid metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
benzene-containing compound metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
long-chain fatty acid biosynthetic process	1
cellular response to stress	1
detoxification of nitrogen compound	1
cellular detoxification	1
sulfur compound biosynthetic process	1
primary metabolic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
identical protein binding	1
protein dimerization activity	1
anion binding	1
modified amino acid binding	1
oligopeptide binding	1
sulfur compound binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTM1	SPP1	P10451	981
GSTM1	AP4M1	O00189	922
GSTM1	CYP1A1	P04798	919
GSTM1	AP5M1	Q9H0R1	915
GSTM1	SLCO6A1	Q86UG4	892
GSTM1	AP1M1	Q9BXS5	855
GSTM1	EPHX1	P07099	849
GSTM1	GSTZ1	O43708	841
GSTM1	NAT2	P11245	772
GSTM1	CYP2E1	P05181	771
GSTM1	GSTT2B	P0CG30	770
GSTM1	AP2M1	P20172	724
GSTM1	NQO1	P15559	720
GSTM1	AP3M2	P53677	711
GSTM1	MAP3K5	Q99683	701

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MAP3K5	GSTM1	psi-mi:“MI:0915”(physical association)	0.400
GSTM1	GSTM3	psi-mi:“MI:0915”(physical association)	0.370
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
GSTM5	GSTM1	psi-mi:“MI:0914”(association)	0.350
GSTM2	GSTM1	psi-mi:“MI:0914”(association)	0.350
GSTM1		psi-mi:“MI:0915”(physical association)	0.000
GSTM1	spr	psi-mi:“MI:0915”(physical association)	0.000
	GSTM1	psi-mi:“MI:0915”(physical association)	0.000
GSTM1	gntR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), MAP3K5 (Affinity Capture-Western), GSTM1 (Reconstituted Complex), GSTM1 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PR19, A6QQZ0, O09131, O65857, O76483, O88741, P09488, P0CG29, P0CG30, P21266, P28161, P28342, P30109, P30568, P30713, P42760, P46409, P46430, P46439, P46440, P48774, P57108, P78417, Q01579, Q03013, Q03425, Q03662, Q4V8E6, Q5BK56, Q5R8E8, Q61133, Q64471, Q84TK0, Q8R5I6, Q8TB36, Q9BEA9, Q9BEB0, Q9C6C8, Q9D4P7, Q9FE46

Diamond homologs: M1RIR6, O35543, O35660, P00502, P04905, P08009, P08010, P08515, P09488, P10649, P15626, P15964, P16413, P19639, P20136, P21266, P28161, P30112, P30116, P31670, P31671, P35661, P46409, P46419, P46427, P46436, P46439, P48774, P51781, P56598, P86214, Q00285, Q03013, Q5BK56, Q5R8E8, Q80W21, Q8JFZ2, Q8R5I6, Q9BEA9, Q9BEB0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MYB	“up-regulates quantity by expression”	GSTM1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1411 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109688671:A:AG	acceptor_gain	1.0000
1:109688672:G:GG	acceptor_gain	1.0000
1:109688738:G:GG	donor_gain	1.0000
1:109689125:CCTGT:C	donor_gain	1.0000
1:109689126:CTGT:C	donor_gain	1.0000
1:109689128:GT:G	donor_gain	1.0000
1:109689130:G:GG	donor_gain	1.0000
1:109689130:GT:G	donor_loss	1.0000
1:109689131:T:TG	donor_loss	1.0000
1:109689132:G:GG	donor_loss	1.0000
1:109689134:GT:G	donor_gain	1.0000
1:109689215:T:TA	acceptor_gain	1.0000
1:109689216:G:A	acceptor_gain	1.0000
1:109689222:CAG:C	acceptor_loss	1.0000
1:109689223:AG:A	acceptor_gain	1.0000
1:109689223:AGGT:A	acceptor_gain	1.0000
1:109689224:G:GT	acceptor_gain	1.0000
1:109689224:GG:G	acceptor_gain	1.0000
1:109689224:GGT:G	acceptor_gain	1.0000
1:109689224:GGTG:G	acceptor_gain	1.0000
1:109689321:AATTT:A	donor_gain	1.0000
1:109689322:ATTT:A	donor_gain	1.0000
1:109689323:TTT:T	donor_gain	1.0000
1:109689323:TTTGT:T	donor_loss	1.0000
1:109689324:TT:T	donor_gain	1.0000
1:109689325:TG:T	donor_loss	1.0000
1:109689326:G:GG	donor_gain	1.0000
1:109689326:GTGA:G	donor_loss	1.0000
1:109689327:TGAG:T	donor_loss	1.0000
1:109689328:GAGTG:G	donor_loss	1.0000

AlphaMissense

1457 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109688696:T:A	W46R	0.983
1:109688696:T:C	W46R	0.983
1:109687895:T:A	W8R	0.974
1:109687895:T:C	W8R	0.974
1:109687897:G:C	W8C	0.970
1:109687897:G:T	W8C	0.970
1:109690466:G:C	D157H	0.965
1:109690469:T:C	F158L	0.965
1:109690471:T:A	F158L	0.965
1:109690471:T:G	F158L	0.965
1:109687892:T:C	Y7H	0.964
1:109690331:T:C	F141L	0.963
1:109690333:T:A	F141L	0.963
1:109690333:T:G	F141L	0.963
1:109687907:G:A	G12R	0.961
1:109687907:G:C	G12R	0.961
1:109689112:C:A	A81D	0.961
1:109688729:T:C	F57L	0.960
1:109688731:T:A	F57L	0.960
1:109688731:T:G	F57L	0.960
1:109689049:T:C	L60P	0.959
1:109687889:G:T	G6W	0.958
1:109690467:A:C	D157A	0.958
1:109687908:G:A	G12E	0.957
1:109688698:G:C	W46C	0.956
1:109688698:G:T	W46C	0.956
1:109689115:G:C	R82P	0.956
1:109687904:C:A	R11S	0.954
1:109689049:T:A	L60Q	0.953
1:109690468:T:A	D157E	0.953

dbSNP variants (sampled 300 via entrez): RS1012880758 (1:109689410 C>G,T), RS1019715646 (1:109687712 C>T), RS1023808626 (1:109689744 A>C), RS1030746528 (1:109690955 A>G), RS1038446815 (1:109693786 C>T), RS1055860922 (1:109686767 C>A), RS1056806 (1:109690525 C>T), RS1065410 (1:109688217 T>C), RS1065411 (1:109690516 G>A,C,T), RS10857795 (1:109688145 G>A,C,T), RS10857796 (1:109692410 A>G), RS11101983 (1:109690625 T>C,G), RS111384689 (1:109688776 A>G), RS111436983 (1:109690435 T>C), RS111471552 (1:109688447 G>A)

Disease associations

OMIM: gene MIM:138350 | 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
GCST000842_10	Bladder cancer	5.000000e-31
GCST006585_2491	Blood protein levels	7.000000e-07
GCST90002393_42	Monocyte count	3.000000e-16
GCST90002395_314	Mean platelet volume	3.000000e-13
GCST90002397_766	Mean spheric corpuscular volume	1.000000e-09
GCST90002402_485	Platelet count	2.000000e-14
GCST90013405_3	Liver enzyme levels (alanine transaminase)	4.000000e-21
GCST90013663_99	Alanine aminotransferase levels	7.000000e-22
GCST90013664_59	Aspartate aminotransferase levels	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0004309	platelet count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2081 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
GSTM1 non-null, GSTM1 null	Toxicity	3	cisplatin	Deafness;Ototoxicity;Testicular Neoplasms
GSTM1 non-null, GSTM1 null	Efficacy,Toxicity	3	bleomycin;dacarbazine;doxorubicin;vinblastine
GSTM1 non-null, GSTM1 null	Toxicity	3	clozapine
GSTM1 non-null, GSTM1 null	Toxicity	3	nevirapine	HIV infectious disease;Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
GSTM1 non-null, GSTM1 null	Efficacy	3	cisplatin;oxaliplatin;Platinum compounds	Neoplasms
GSTM1 non-null, GSTM1 null	Toxicity	3	sulfamethoxazole / trimethoprim	Acquired Immunodeficiency Syndrome
GSTM1 non-null, GSTM1 null	Toxicity	4	Drugs For Treatment Of Tuberculosis;ethambutol;isoniazid;pyrazinamide;rifampin;streptomycin	Tuberculosis
rs3754446	Metabolism/PK	3	busulfan	Leukemia;Myeloid;Acute

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3754446	GSTM1, GSTM5	3	0.00	1	busulfan

Binding affinities (BindingDB)

221 measured of 223 human assays (224 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(5Z)-3-[2-(1H-indol-3-yl)ethyl]-2-(4-methoxyphenyl)imino-5-[(5-morpholin-4-ylfuran-2-yl)methylidene]-1,3-thiazolidin-4-one	EC50	26.9 nM
(5Z)-3-[2-(1H-indol-3-yl)ethyl]-5-[(5-morpholin-4-ylfuran-2-yl)methylidene]-2-phenylimino-1,3-thiazolidin-4-one	EC50	69.7 nM
(E)-2-(4-bromophenyl)-3-(2,5-dimethoxy-4-pyrrolidin-1-yl-phenyl)prop-2-enenitrile	EC50	74.5 nM
(5Z)-5-(2,5-dimethoxy-4-pyrrolidino-benzylidene)-3-(3-methoxypropyl)-2-phenylimino-thiazolidin-4-one	EC50	110 nM
MLS000728818	EC50	151 nM
1-(3,4-dihydro-2H-quinolin-1-yl)-2-[[3-(3-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]sulfanyl]ethanone	EC50	160 nM
2,5-bis(chloranyl)-3-(4-methylpiperazin-1-yl)-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	160 nM
2-chloranyl-3-[[4-(diethylamino)phenyl]amino]naphthalene-1,4-dione	EC50	170 nM
5-bromo-2-furaldehyde (1,1-dioxido-1,2-benzisothiazol-3-yl)(methyl)hydrazone	EC50	184 nM
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
(2Z)-1-ethyl-2-[(E)-3-(1-ethyl-2-benzo[e][1,3]benzoxazol-1-iumyl)prop-2-enylidene]benzo[e][1,3]benzoxazole;4-methylbenzenesulfonate	EC50	223 nM
(4E)-4-[[4-[ethyl(isopropyl)amino]anilino]methylene]-2-p-anisyl-isoquinoline-1,3-quinone	EC50	249 nM
2,6,7-trihydroxy-9-(2,4,5-trimethoxyphenyl)-3-xanthenone	EC50	258 nM
6,7-dimethoxy-4-[2-(4-methylphenyl)ethylamino]-1H-quinazoline-2-thione	EC50	334 nM
(2E)-1-phenyl-3-[4-(3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)phenyl]prop-2-en-1-one	EC50	340 nM
9-(4-methylphenyl)-5-{[3-(4-morpholinyl)propyl]amino}-8H-thieno[2’,3’:4,5]pyrimido[2,1-a]phthalazin-8-one	EC50	346 nM
5-(3-pyridinylmethylamino)-8-quinazolino[2,3-a]phthalazinone	EC50	348 nM
3-[(2-amino-3-thiophen-2-ylsulfonyl-1-pyrrolo[3,2-b]quinoxalinyl)iminomethyl]phenol	EC50	355 nM
4-(1H-imidazol-5-yl)-2,6-dinitro-aniline	EC50	391 nM
MLS000711688	EC50	481 nM
4-[2-[(6,7-dimethoxy-2-sulfanylidene-1H-quinazolin-4-yl)amino]ethyl]benzenesulfonamide	EC50	540 nM
5-[(3-chlorobenzoyl)amino]-2-[(E)-2-(3,5-dimethylanilino)vinyl]-6-keto-pyran-3-carboxylic acid methyl ester	EC50	567 nM
3-amino-2-(4-bromobenzoyl)-6-keto-7H-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester	EC50	574 nM
(5Z)-3-butyl-5-[(2E,4E)-5-phenylazanylpenta-2,4-dienylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	EC50	576 nM
3-(3-chloro-4-methoxybenzyl)-4-imino-6,7-dimethoxy-3,4-dihydro-2(1H)-quinazolinethione	EC50	602 nM
1-[(3,4-dimethoxyphenyl)methylideneamino]-3-thiophen-2-ylsulfonyl-2-pyrrolo[3,2-b]quinoxalinamine	EC50	612 nM
(4E)-2-methoxy-4-[[(6-methyl-1-phenyl-4-pyrazolo[3,4-d]pyrimidinyl)hydrazo]methylidene]-1-cyclohexa-2,5-dienone	EC50	638 nM
10-oxo-N-(thien-2-ylmethyl)-10H-pyrido[1,2-a]thieno[3,2-d]pyrimidine-5-carboxamide	EC50	664 nM
4-[[4-(2-methyl-3-imidazo[1,2-a]pyrimidinyl)-2-thiazolyl]amino]phenol;hydrobromide	EC50	670 nM
1-(2,1,3-benzothiadiazol-4-yl)-3-[(3,4-dimethoxyphenyl)methylideneamino]urea	EC50	682 nM
(5Z)-5-{[4-(dimethylamino)phenyl]imino}-1-(3-hydroxypropyl)-4-methyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile	EC50	760 nM
(2-methoxyphenyl)-[4-(2-methylimidazo[1,2-a]pyrimidin-3-yl)thiazol-2-yl]amine;hydrobromide	EC50	820 nM
(4E)-4-[[2-[2-(3,5-dimethylpyrazol-1-yl)-6-methyl-pyrimidin-4-yl]hydrazinyl]methylidene]-3-oxidanyl-cyclohexa-2,5-dien-1-one	EC50	831 nM
MLS000591719	EC50	950 nM
3,4,5-trihydroxybenzoic acid [(3R,4S,5S,6S)-3,4,5,6-tetragalloyloxytetrahydropyran-2-yl]methyl ester	EC50	951 nM
(5E)-2-(4-hydroxyanilino)-5-(4-hydroxy-3,5-dimethoxy-benzylidene)-2-thiazolin-4-one	EC50	974 nM
(m-anisylideneamino)-([1,2,4]triazolo[3,4-a]phthalazin-6-yl)amine	EC50	980 nM
1-(3-chlorophenyl)-3-(2-pyridin-3-ylpyrimidin-4-yl)urea	EC50	1110 nM
6-(3,4-Dimethoxy-phenyl)-3-furan-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine	EC50	1210 nM
(3E)-2-amino-3-[(3-methoxyphenyl)hydrazinylidene]-5,6,7,8-tetrahydropyrazolo[5,1-b]quinazolin-9-one	EC50	1220 nM
3-(2-{(E)-[1-(4-chlorophenyl)-2,5-dioxoimidazolidin-4-ylidene]methyl}-1H-pyrrol-1-yl)benzoic acid	IC50	1230 nM
1-(1-pyrrolidinyl)-2-[(3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thio]ethanone	EC50	1300 nM
4-(cycloheptylamino)-6,7-dimethoxy-1H-quinazoline-2-thione	EC50	1320 nM
MLS000516682	EC50	1330 nM
3-(2-furanyl)-5-[(E)-2-(4-nitrophenyl)ethenyl]-2-phenyl-3,4-dihydropyrazole	EC50	1340 nM
(5Z)-5-(2,5-dimethoxy-4-pyrrolidino-benzylidene)-3-(2-methoxyethyl)-2-phenylimino-thiazolidin-4-one	EC50	1390 nM
2-(4-Phenyl-thiazol-2-yl)-benzo[f]chromen-3-ylideneamine	EC50	1400 nM
2-amino-3-[(4-hydroxyphenyl)diazenyl]-7-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one	EC50	1400 nM
4-[2-[1-(1,3-benzodioxol-5-yl)ethylidene]hydrazinyl]-3-nitro-benzenesulfonamide	EC50	1400 nM
1-[(5-nitro-2-oxidanylidene-indol-3-yl)amino]-3-propan-2-yl-thiourea	EC50	1430 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 14 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Ki	2000	nM	CHEMBL58135
5.68	Ki	2100	nM	CHEMBL301229
5.50	Ki	3200	nM	CHEMBL1938641
5.33	Ki	4700	nM	CHEMBL1938641

PubChem BioAssay actives

4 with measured affinity, of 55 total; 3 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
2-amino-5-[[1-(carboxymethylamino)-3-hexylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75274: Inhibitory activity was measured on recombinant human Glutathione S-transferase Mu 1	ki	2.0000	uM
2-amino-5-[[1-(2-carboxyethylamino)-3-[(4-methylphenyl)methylsulfanyl]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75274: Inhibitory activity was measured on recombinant human Glutathione S-transferase Mu 1	ki	2.1000	uM
[(3S,4R,5R)-3-decoxy-4,5-dihydroxy-6-oxocyclohexen-1-yl]methyl acetate	642147: Competitive inhibition of human GSTM1 using GSH as substrate by Lineweaver-Burk plot analysis	ki	3.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Glutathione	affects binding, decreases reaction, decreases abundance, affects cotreatment, affects metabolic processing (+1 more)	11
Benzo(a)pyrene	increases mutagenesis, increases reaction, affects activity, affects methylation, affects response to substance (+6 more)	9
Pesticides	affects response to substance, increases abundance, increases response to substance	8
Arsenic	decreases response to substance, affects metabolic processing, affects response to substance, affects abundance, affects methylation	7
Benzene	increases response to substance, affects metabolic processing, affects abundance, increases metabolic processing, affects response to substance (+1 more)	7
Ozone	affects response to substance, increases reaction, increases response to substance, decreases expression, decreases reaction (+4 more)	7
Busulfan	affects cotreatment, affects metabolic processing, increases response to substance, affects abundance, affects response to substance	6
Mercury	decreases expression, increases abundance, affects abundance, affects response to substance, affects cotreatment	6
Polycyclic Aromatic Hydrocarbons	affects secretion, affects response to substance, affects metabolic processing, decreases activity, increases response to substance	6
Cisplatin	affects cotreatment, decreases response to substance, increases expression, affects response to substance	5
Styrene	affects response to substance, increases reaction, increases response to substance, affects metabolic processing, affects reaction	5
styrene oxide	affects metabolic processing, decreases response to substance	4
sulforaphane	affects response to substance, affects metabolic processing, decreases reaction, increases expression	4
Dinitrochlorobenzene	affects binding, affects metabolic processing, increases glutathionylation	4
Particulate Matter	increases phosphorylation, decreases response to substance, decreases expression, increases abundance, affects response to substance (+2 more)	4
S-phenyl-N-acetylcysteine	affects abundance, affects reaction, affects cotreatment	3
Arsenic Trioxide	decreases response to substance, increases expression	3
Air Pollutants	decreases expression, increases abundance, affects response to substance, decreases reaction, increases degradation (+1 more)	3
Azathioprine	affects response to substance, affects metabolic processing	3
Cadmium	decreases response to substance, increases expression, increases response to substance, decreases expression, increases abundance (+1 more)	3
Hydrocarbons, Chlorinated	affects response to substance, increases abundance	3
Lead	decreases methylation, affects cotreatment, increases expression, increases reaction, increases response to substance (+1 more)	3
Tretinoin	decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, affects cotreatment, affects metabolic processing, decreases activity	3
Acrylamide	affects metabolic processing, affects chemical synthesis, decreases expression, affects cotreatment	3
methyleugenol	decreases activity, decreases expression	2
bisphenol A	decreases expression, increases response to substance	2
decabromobiphenyl ether	increases expression, decreases expression	2
benzo(k)fluoranthene	decreases expression, affects cotreatment	2
phenanthrene	increases metabolic processing, increases reaction, affects metabolic processing	2

ChEMBL screening assays

14 unique, capped per target: 12 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1033246	Binding	Specific activity of human recombinant Glutathione S-transferase Mu 1 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
CHEMBL1743227	ADMET	Substrates for human cytosolic glutathione transferase GSTM1	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.