GSTA2

Summary

GSTA2 (glutathione S-transferase alpha 2, HGNC:4627) is a protein-coding gene on chromosome 6p12.2, encoding Glutathione S-transferase A2 (P09210). Catalyzes the conjugation of glutathione to a large variety of electrophilic compounds.

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes 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 some drugs. 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-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation.

Source: NCBI Gene 2939 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_000846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4627
Approved symbol	GSTA2
Name	glutathione S-transferase alpha 2
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000244067
Ensembl biotype	protein_coding
OMIM	138360
Entrez	2939

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000493422, ENST00000873253, ENST00000873254, ENST00000873255, ENST00000873256, ENST00000873257, ENST00000873258, ENST00000873259, ENST00000873260, ENST00000873261, ENST00000873262

RefSeq mRNA: 1 — MANE Select: NM_000846 NM_000846

CCDS: CCDS4944

Canonical transcript exons

ENST00000493422 — 7 exons

Exon	Start	End
ENSE00001838236	52750087	52750699
ENSE00002430705	52752854	52752995
ENSE00002436406	52751577	52751708
ENSE00002443554	52763444	52763475
ENSE00002460854	52757861	52757977
ENSE00002511182	52754943	52755075
ENSE00002528254	52756258	52756309

Expression profiles

Bgee: expression breadth broad, 91 present calls, max score 98.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.8511 / max 2488.5416, expressed in 121 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73973	3.8511	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.68	gold quality
duodenum	UBERON:0002114	98.45	gold quality
pancreas	UBERON:0001264	97.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.01	gold quality
gall bladder	UBERON:0002110	96.97	gold quality
islet of Langerhans	UBERON:0000006	96.05	gold quality
liver	UBERON:0002107	95.32	gold quality
adult mammalian kidney	UBERON:0000082	94.85	gold quality
right lobe of liver	UBERON:0001114	94.26	gold quality
right testis	UBERON:0004534	91.68	gold quality
left testis	UBERON:0004533	90.70	gold quality
testis	UBERON:0000473	90.43	gold quality
trachea	UBERON:0003126	87.25	gold quality
kidney	UBERON:0002113	86.18	gold quality
vastus lateralis	UBERON:0001379	83.68	gold quality
small intestine	UBERON:0002108	82.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.41	gold quality
quadriceps femoris	UBERON:0001377	80.54	gold quality
right adrenal gland	UBERON:0001233	76.56	gold quality
epithelium of bronchus	UBERON:0002031	76.54	gold quality
metanephros cortex	UBERON:0010533	75.96	gold quality
metanephric glomerulus	UBERON:0004736	75.28	gold quality
right adrenal gland cortex	UBERON:0035827	74.11	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.03	gold quality
left adrenal gland	UBERON:0001234	72.34	gold quality
cerebellar vermis	UBERON:0004720	71.67	gold quality
left adrenal gland cortex	UBERON:0035825	71.31	gold quality
cortex of kidney	UBERON:0001225	71.23	gold quality
adrenal gland	UBERON:0002369	69.76	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	5465.45
E-MTAB-5061	yes	1479.62
E-ENAD-27	yes	635.08
E-GEOD-125970	yes	367.47
E-MTAB-10553	yes	38.86
E-GEOD-81547	yes	23.74
E-MTAB-9388	yes	12.06
E-HCAD-31	yes	5.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, HNF1A, IRF6, NCOR2, NR1H4, NR3C1, PPARG, ZNF384

miRNA regulators (miRDB)

36 targeting GSTA2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-1262	98.17	66.52	757

Literature-anchored findings (GeneRIF, showing 14)

• Polymorphism identified in the proximal promoter of GSTA2 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)
• transmutation into an efficient steroid isomerase (PMID:12023294)
• 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)
• Overexpression of GSTA2 by transient transfection protected Colo 320HSR cells against both cycle arrest and apoptosis following exposure to HN2. (PMID:15778998)
• no association was observed between individual GSTA2 polymorphisms and haplotypes and individual susceptibility to breast cancer. (PMID:19639209)
• it is unlikely that glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 participate in breast cancer susceptibility. (PMID:19859803)
• The 3D structures of human GSTs A2-2 and A3-3 in complex with Delta(4)-androstene-3-17-dione, were solved. (PMID:20083122)
• studied the five known allelic variants of human glutathione transferase A2-2 (GST A2-2) (EC 2.5.1.18), abundantly expressed in liver and efficiently catalyzing the bioactivation of azathioprine to release 6-mercaptopurine (PMID:20434437)
• Even with typical substrates, the astonishing concentration of glutathione transferase present in hepatocytes, causes an unusual “inverted” kinetics whereby the classical trends of v versus E and v versus S are reversed (PMID:21163259)
• Single nucleotide polymorphism in GSTA2 is associated with low-stage non-small cell lung cancer. (PMID:21792076)
• By direct resequencing of the 5’-flanking region, all the exons, and their flanking introns for 107 patients, 29 and 27 variants were identified in GSTA1 and GSTA2, respectively. (PMID:21844655)
• Data indicate that steroidogenic factor 1 (SF-1) and glutathione S-transferase A (GSTA) family genes (hGSTA1-hGSTA4) are involved in steroidogenesis. (PMID:23650189)
• the GSTA2 S112T polymorphism is predictive of transplant outcome in patients receiving busulfan in the preparative regimen, at least in association with cyclophosphamide. (PMID:24056816)

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), GSTA1 (ENSG00000243955)

Protein

Protein identifiers

Glutathione S-transferase A2 — P09210 (reviewed: P09210)

Alternative names: GST HA subunit 2, GST class-alpha member 2, GST-gamma, GSTA2-2, GTH2

All UniProt accessions (2): A0A140VKE2, P09210

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conjugation of glutathione to a large variety of electrophilic compounds.

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

Subcellular location. Cytoplasm.

Tissue specificity. Liver.

Similarity. Belongs to the GST superfamily. Alpha family.

RefSeq proteins (1): NP_000837* (*=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), 1 shown:

• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)

UniProt features (41 total): helix 11, strand 6, sequence conflict 5, sequence variant 4, binding site 4, turn 3, modified residue 2, domain 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2VCT	X-RAY DIFFRACTION	2.1
4ACS	X-RAY DIFFRACTION	2.1
2WJU	X-RAY DIFFRACTION	2.3
1AGS	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09210-F1	97.70	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 (2): 2, 4

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9748787	Azathioprine ADME

MSigDB gene sets: 107 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_545, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, chr6p12, MARTINEZ_RB1_TARGETS_DN, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_AMIDE_METABOLIC_PROCESS, TGCTGAY_UNKNOWN, HSIAO_LIVER_SPECIFIC_GENES

GO Biological Process (3): glutathione metabolic process (GO:0006749), xenobiotic metabolic process (GO:0006805), epithelial cell differentiation (GO:0030855)

GO Molecular Function (3): glutathione transferase activity (GO:0004364), protein binding (GO:0005515), transferase activity (GO:0016740)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Interleukin-12 signaling	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
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
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
binding	1
catalytic activity	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTA2	GSTZ1	O43708	812
GSTA2	SLCO6A1	Q86UG4	788
GSTA2	UGT1A8	Q9HAW9	643
GSTA2	GCLC	P48506	635
GSTA2	MEP1A	Q16819	619
GSTA2	NQO1	P15559	604
GSTA2	GSTT2B	P0CG30	603
GSTA2	SULT2A1	Q06520	600
GSTA2	MEP1B	Q16820	586
GSTA2	GSTO1	P78417	581
GSTA2	GSTM1	P09488	547
GSTA2	GCLM	P48507	529
GSTA2	UGT1A6	P19224	522
GSTA2	GSTA1	P08263	505
GSTA2	NFE2L2	Q16236	502

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GSTA2	GSTA4	psi-mi:“MI:0915”(physical association)	0.920
GSTA2	GSTA4	psi-mi:“MI:0914”(association)	0.920
GSTA4	GSTA2	psi-mi:“MI:0915”(physical association)	0.920
GSTA2	GSTA5	psi-mi:“MI:0915”(physical association)	0.740
GIN1	GSTA2	psi-mi:“MI:0915”(physical association)	0.400
NUSAP1	GAPDHS	psi-mi:“MI:0914”(association)	0.350
STEEP1	GSTA2	psi-mi:“MI:0914”(association)	0.350
GSTA2	GSTA4	psi-mi:“MI:0915”(physical association)	0.000
GSTA2	GSTA5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): GSTA4 (Two-hybrid), GSTA5 (Affinity Capture-MS), GSTA3 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), GSTA2 (Affinity Capture-MS), GSTA4 (Two-hybrid), GSTA5 (Affinity Capture-MS), GSTA3 (Affinity Capture-MS), GSTA4 (Affinity Capture-MS), ATG4C (Affinity Capture-MS), GSTA2 (Affinity Capture-MS), GSTA2 (Two-hybrid), GSTA2 (Two-hybrid), GSTA2 (Affinity Capture-MS), ATG4C (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

799 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52751620:T:TA	donor_gain	1.0000
6:52751708:CCTG:C	acceptor_loss	1.0000
6:52751709:C:CC	acceptor_gain	1.0000
6:52751709:CTGG:C	acceptor_loss	1.0000
6:52752849:CTTA:C	donor_gain	1.0000
6:52752850:TTA:T	donor_loss	1.0000
6:52752851:TA:T	donor_loss	1.0000
6:52752852:A:AC	donor_gain	1.0000
6:52752852:ACTTT:A	donor_loss	1.0000
6:52752853:C:CG	donor_gain	1.0000
6:52752853:CT:C	donor_gain	1.0000
6:52752853:CTT:C	donor_gain	1.0000
6:52752853:CTTT:C	donor_gain	1.0000
6:52752853:CTTTT:C	donor_gain	1.0000
6:52752933:C:CC	acceptor_gain	1.0000
6:52752991:CAATC:C	acceptor_gain	1.0000
6:52752994:TC:T	acceptor_gain	1.0000
6:52752994:TCC:T	acceptor_loss	1.0000
6:52752995:CC:C	acceptor_gain	1.0000
6:52752995:CCTG:C	acceptor_loss	1.0000
6:52752996:C:A	acceptor_loss	1.0000
6:52752996:C:CC	acceptor_gain	1.0000
6:52754941:A:AC	donor_gain	1.0000
6:52754942:C:CC	donor_gain	1.0000
6:52754942:CAGGG:C	donor_gain	1.0000
6:52754952:T:TA	donor_gain	1.0000
6:52754965:T:A	donor_gain	1.0000
6:52755073:CAT:C	acceptor_gain	1.0000
6:52755075:TCTTT:T	acceptor_loss	1.0000
6:52755076:C:CC	acceptor_gain	1.0000

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52755059:G:C	F52L	0.988
6:52755059:G:T	F52L	0.988
6:52755061:A:G	F52L	0.988
6:52757887:A:G	W21R	0.988
6:52757887:A:T	W21R	0.988
6:52750655:A:C	F197L	0.987
6:52750655:A:T	F197L	0.987
6:52750657:A:G	F197L	0.987
6:52756307:A:C	F30L	0.986
6:52756307:A:T	F30L	0.986
6:52756309:A:G	F30L	0.986
6:52757889:C:G	R20P	0.977
6:52751644:A:G	L160P	0.976
6:52755042:A:T	V58D	0.976
6:52755014:C:A	Q67H	0.972
6:52755014:C:G	Q67H	0.972
6:52751661:G:C	S154R	0.971
6:52751661:G:T	S154R	0.971
6:52751663:T:G	S154R	0.971
6:52752976:C:G	G98R	0.971
6:52751654:C:G	D157H	0.967
6:52754988:G:T	A76D	0.965
6:52751656:G:T	A156D	0.964
6:52755060:A:G	F52S	0.964
6:52755061:A:T	F52I	0.964
6:52750634:C:A	R204S	0.963
6:52750634:C:G	R204S	0.963
6:52755048:G:T	P56Q	0.963
6:52750695:A:G	L184P	0.962
6:52754989:C:G	A76P	0.962

dbSNP variants (sampled 300 via entrez): RS1000887948 (6:52756680 G>T), RS1001021046 (6:52752278 G>A), RS1001236861 (6:52756431 C>A,T), RS1001293061 (6:52763701 C>A), RS1001555471 (6:52759274 A>G), RS1001692608 (6:52754201 T>C), RS1001704044 (6:52754332 A>G), RS1001858198 (6:52749834 A>G), RS1001899923 (6:52759020 A>C), RS1002290843 (6:52750085 C>G,T), RS1002395634 (6:52749688 C>T), RS1002527268 (6:52752015 C>T), RS1003069815 (6:52751842 T>C), RS1003244918 (6:52764816 C>T), RS1003345257 (6:52755095 A>T)

Disease associations

OMIM: gene MIM:138360 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST008058_254	Estimated glomerular filtration rate	5.000000e-13
GCST008059_186	Estimated glomerular filtration rate	2.000000e-12
GCST008074_136	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-08
GCST008074_143	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-12
GCST008076_47	Triglyceride levels	9.000000e-07
GCST008078_45	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-07
GCST008079_132	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-06
GCST008079_71	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-07
GCST008083_11	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-10
GCST008083_94	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9.000000e-14
GCST008084_170	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-08
GCST008084_52	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-07
GCST008087_25	Triglyceride levels in current drinkers	3.000000e-08
GCST010083_310	Hemoglobin levels	1.000000e-20
GCST010083_362	Hemoglobin levels	2.000000e-16
GCST010241_331	Apolipoprotein A1 levels	3.000000e-08
GCST010244_237	Triglyceride levels	7.000000e-18
GCST011345_7	Triglyceride levels	1.000000e-09
GCST90002404_263	Red cell distribution width	2.000000e-16
GCST90016666_2	Liver volume	1.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2241 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2180314	GSTA2		0.00	0

ChEMBL bioactivities

3 potent at pChembl≥5 of 16 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	IC50	5	nM	CHEMBL405395
5.39	IC50	4100	nM	CHEMBL174893
5.08	IC50	8400	nM	CHEMBL359933

PubChem BioAssay actives

3 with measured affinity, of 49 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
(4S)-4-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1H-indol-3-yl)propanoyl]amino]-5-[[1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]cyclopropyl]amino]-5-oxopentanoic acid	75154: Inhibition of p53 binding to Glutathione S-transferase 2 (hdm2-GST)	ic50	0.0050	uM
2-amino-5-[[1-(carboxymethylamino)-1-oxo-3-(5-oxohexan-3-ylsulfanyl)propan-2-yl]amino]-5-oxopentanoic acid	75153: The compound was tested for it’s inhibitory activity against Onchocerca volvulus Glutathione S-transferase 2	ic50	4.1000	uM
2-amino-5-[[1-(carboxymethylamino)-1-oxo-3-(2-oxoheptan-4-ylsulfanyl)propan-2-yl]amino]-5-oxopentanoic acid	75153: The compound was tested for it’s inhibitory activity against Onchocerca volvulus Glutathione S-transferase 2	ic50	8.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
cumene hydroperoxide	decreases metabolic processing, increases metabolic processing	3
Dinitrochlorobenzene	increases metabolic processing, decreases metabolic processing	3
Aflatoxin B1	decreases expression, decreases methylation	3
Azathioprine	affects response to substance, affects metabolic processing	2
Butyrates	increases expression	2
Diethylhexyl Phthalate	affects cotreatment, increases expression	2
Glutathione	affects metabolic processing, affects cotreatment, increases metabolic processing	2
Lipid Peroxides	affects metabolic processing, decreases response to substance, decreases abundance	2
tert-Butylhydroperoxide	increases metabolic processing, decreases metabolic processing	2
bisphenol F	affects cotreatment, decreases expression	1
perfluorodecanesulfonic acid	increases expression	1
bismuth tripotassium dicitrate	decreases expression	1
testosterone enanthate	affects cotreatment, decreases expression	1
alternariol	affects localization	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
diisononyl phthalate	affects cotreatment, increases expression	1
hydroxyhydroquinone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
lead nitrate	affects cotreatment, increases expression	1
alternariol monomethyl ether	affects localization	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
4-nitrophenol	increases metabolic processing	1
nonylphenol	increases expression	1
butylbenzyl phthalate	affects cotreatment, increases expression	1
4-vinylpyridine	decreases metabolic processing	1
iprodione	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743223	ADMET	Substrates for human cytosolic glutathione transferase GSTA2	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL1941296	Binding	Inhibition of human GSTA2 using GSH as substrate after 3 mins by spectrophotometry	Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery