GSTT2B

Summary

GSTT2B (glutathione S-transferase theta 2B, HGNC:33437) is a protein-coding gene on chromosome 22q11.23, encoding Glutathione S-transferase theta-2B (P0CG30). Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.

The protein encoded by this gene, glutathione S-transferase (GST) theta 2B (GSTT2B), is a member of a superfamily of proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. Human GSTs can be divided into five main classes: alpha, mu, pi, theta, and zeta. The theta class includes GSTT1, GSTT2, and GSTT2B. GSTT2 and GSTT2B are nearly identical to each other, and share 55% amino acid identity with GSTT1. All three genes may play a role in human carcinogenesis. The GSTT2B gene is a pseudogene in some populations.

Source: NCBI Gene 653689 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001080843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33437
Approved symbol	GSTT2B
Name	glutathione S-transferase theta 2B
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	GSTT2P
Ensembl gene	ENSG00000133433
Ensembl biotype	protein_coding
Entrez	653689

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000290765, ENST00000404172, ENST00000895419, ENST00000932445, ENST00000964515

RefSeq mRNA: 2 — MANE Select: NM_001080843 NM_001080843, NM_001363804

CCDS: CCDS33617, CCDS87010

Canonical transcript exons

ENST00000290765 — 5 exons

Exon	Start	End
ENSE00001727999	23958285	23958458
ENSE00001734445	23958551	23958701
ENSE00001749600	23960294	23960381
ENSE00001833725	23961020	23961195
ENSE00001883656	23957414	23957932

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.33.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9431 / max 37.6472, expressed in 529 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191349	0.9431	529

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.33	gold quality
right adrenal gland cortex	UBERON:0035827	94.58	gold quality
right adrenal gland	UBERON:0001233	94.03	gold quality
adrenal tissue	UBERON:0018303	94.02	gold quality
left adrenal gland	UBERON:0001234	93.51	gold quality
apex of heart	UBERON:0002098	92.85	gold quality
adrenal gland	UBERON:0002369	92.02	gold quality
left adrenal gland cortex	UBERON:0035825	91.80	gold quality
fundus of stomach	UBERON:0001160	90.92	gold quality
right lobe of liver	UBERON:0001114	90.43	gold quality
adenohypophysis	UBERON:0002196	89.60	gold quality
stromal cell of endometrium	CL:0002255	89.57	gold quality
prostate gland	UBERON:0002367	88.91	gold quality
pituitary gland	UBERON:0000007	88.78	gold quality
left coronary artery	UBERON:0001626	88.48	gold quality
right frontal lobe	UBERON:0002810	88.26	gold quality
right atrium auricular region	UBERON:0006631	88.12	gold quality
right ovary	UBERON:0002118	88.06	gold quality
left ovary	UBERON:0002119	87.87	gold quality
hypothalamus	UBERON:0001898	87.86	gold quality
body of stomach	UBERON:0001161	87.81	gold quality
amygdala	UBERON:0001876	87.76	gold quality
temporal lobe	UBERON:0001871	87.70	gold quality
primary visual cortex	UBERON:0002436	87.67	gold quality
anterior cingulate cortex	UBERON:0009835	87.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.60	gold quality
body of pancreas	UBERON:0001150	87.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.38	gold quality
ascending aorta	UBERON:0001496	87.25	gold quality
right lobe of thyroid gland	UBERON:0001119	87.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting GSTT2B, 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-25-3P	99.98	74.60	1817
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-28-5P	96.16	66.12	579

Literature-anchored findings (GeneRIF, showing 4)

• study describes a previously uncharacterized 38-kilo-base (kb) long deletion polymorphism of GSTT2B located within a 61-kb DNA inverted repeat (PMID:19424424)
• results suggest that the presence of the recently described GSTT2B deletion may have a protective effect on the risk of OSCC in the Mixed Ancestry South African population (PMID:22216261)
• Results GSTT2B insertion allele was associated with an increased risk of being small for gestational age indicate that (PMID:22676722)
• The data highlights that GSTT2B copy number variant is not associated with the investigated complex diseases in Italian patients. (PMID:26207597)

Cross-species orthologs

42 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstr	ENSDARG00000042620
danio_rerio	gstt2	ENSDARG00000095464
mus_musculus	Gstt2	ENSMUSG00000033318
rattus_norvegicus	Gstt2	ENSRNOG00000052415
drosophila_melanogaster	GstD1	FBGN0001149
drosophila_melanogaster	GstD2	FBGN0010038
drosophila_melanogaster	GstD3	FBGN0010039
drosophila_melanogaster	GstD4	FBGN0010040
drosophila_melanogaster	GstD5	FBGN0010041
drosophila_melanogaster	GstD6	FBGN0010042
drosophila_melanogaster	GstD7	FBGN0010043
drosophila_melanogaster	GstD8	FBGN0010044
drosophila_melanogaster	GstE12	FBGN0027590
drosophila_melanogaster	Clic	FBGN0030529
drosophila_melanogaster	GstT3	FBGN0031117
drosophila_melanogaster	GstE13	FBGN0033381
drosophila_melanogaster	GstE1	FBGN0034335
drosophila_melanogaster	GstE11	FBGN0034354
drosophila_melanogaster	GstO3	FBGN0035904
drosophila_melanogaster	GstO2	FBGN0035906
drosophila_melanogaster	GstO1	FBGN0035907
drosophila_melanogaster	GstD9	FBGN0038020
drosophila_melanogaster	GstD10	FBGN0042206
drosophila_melanogaster	GstT1	FBGN0050000
drosophila_melanogaster	GstT2	FBGN0050005
drosophila_melanogaster	GstE9	FBGN0063491
drosophila_melanogaster	GstE8	FBGN0063492
drosophila_melanogaster	GstE7	FBGN0063493
drosophila_melanogaster	GstE6	FBGN0063494
drosophila_melanogaster	GstE5	FBGN0063495
drosophila_melanogaster	GstE4	FBGN0063496
drosophila_melanogaster	GstE3	FBGN0063497
drosophila_melanogaster	GstE2	FBGN0063498
drosophila_melanogaster	GstE10	FBGN0063499
drosophila_melanogaster	se	FBGN0086348
caenorhabditis_elegans	exc-4	WBGENE00001365
caenorhabditis_elegans		WBGENE00001371
caenorhabditis_elegans	gst-43	WBGENE00001791
caenorhabditis_elegans		WBGENE00001792
caenorhabditis_elegans		WBGENE00015337
caenorhabditis_elegans		WBGENE00021817
caenorhabditis_elegans		WBGENE00043097

Paralogs (14): GSTO2 (ENSG00000065621), GSTT2 (ENSG00000099984), GSTZ1 (ENSG00000100577), GDAP1 (ENSG00000104381), CLIC5 (ENSG00000112782), GDAP1L1 (ENSG00000124194), GSTO1 (ENSG00000148834), CLIC2 (ENSG00000155962), CLIC6 (ENSG00000159212), CLIC4 (ENSG00000169504), CLIC3 (ENSG00000169583), CLIC1 (ENSG00000213719), EEF1G (ENSG00000254772), GSTT4 (ENSG00000276950)

Protein

Protein identifiers

Glutathione S-transferase theta-2B — P0CG30 (reviewed: P0CG30)

Alternative names: Glutathione S-transferase theta-2

All UniProt accessions (3): P0CG30, G9J6Q5, Q6ICJ4

UniProt curated annotations — full annotation on UniProt →

Function. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a sulfatase activity.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed at low levels in liver. In lung, expressed at low levels in ciliated bronchiolar cells, alveolar macrophages and alveolar type II cells.

Similarity. Belongs to the GST superfamily. Theta family.

RefSeq proteins (2): NP_001074312, NP_001350733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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
IPR040075	GST_N_Theta	Domain
IPR040077	GST_C_Theta	Domain
IPR040079	Glutathione_S-Trfase	Family
IPR051369	GST_Theta	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 (34 total): helix 13, strand 6, turn 4, binding site 4, sequence conflict 2, domain 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4MPG	X-RAY DIFFRACTION	1.95
1LJR	X-RAY DIFFRACTION	3.2
2LJR	X-RAY DIFFRACTION	3.2
3LJR	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CG30-F1	98.16	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): 40–41; 53–54; 66–67; 104–107

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation

MSigDB gene sets: 25 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, GOBP_AMIDE_METABOLIC_PROCESS, REACTOME_GLUTATHIONE_CONJUGATION, GOBP_GLUTATHIONE_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_METABOLIC_PROCESS, REACTOME_PHASE_II_CONJUGATION_OF_COMPOUNDS, MIR4306, MIR6739_5P, MIR6733_5P, MIR3153, MIR4778_5P, MIR520G_3P_MIR520H, MIR6873_5P, MIR4688

GO Biological Process (1): glutathione metabolic process (GO:0006749)

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

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phase II - Conjugation of compounds	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
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2103 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTT2B	HPGDS	O60760	888
GSTT2B	GSTP1	P09211	791
GSTT2B	FBLN1	P23142	772
GSTT2B	GSTM1	P09488	770
GSTT2B	GSTK1	Q9Y2Q3	747
GSTT2B	GSTO2	Q9H4Y5	741
GSTT2B	GSTO1	P78417	670
GSTT2B	GSTM2	P28161	669
GSTT2B	GSTA4	O15217	652
GSTT2B	GSTM3	P21266	649
GSTT2B	GSTM4	Q03013	643
GSTT2B	SLCO6A1	Q86UG4	643
GSTT2B	GSTA1	P08263	631
GSTT2B	GSTZ1	O43708	630
GSTT2B	GSTM5	P46439	622

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CFTR	GSTT2B	psi-mi:“MI:0915”(physical association)	0.510
GSTT2B	SIRT2	psi-mi:“MI:0914”(association)	0.350
GSTT1	ENSA	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): GSTP1 (Co-fractionation), GSTP1 (Co-fractionation), GSTT2 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), NMD3 (Affinity Capture-MS), CARD9 (Affinity Capture-MS), SIRT2 (Affinity Capture-MS), GSTT2B (Affinity Capture-MS), MOCS2 (Affinity Capture-MS), GSTT2 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), NMD3 (Affinity Capture-MS), CARD9 (Affinity Capture-MS), SIRT2 (Affinity Capture-MS), NFRKB (Co-fractionation)

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: A0A1U8QXK4, A0A6J4B5J2, A2Q127, C8VQ63, P0CG29, P0CG30, P12261, P26641, P26642, P29547, P29694, P36008, P40921, P42936, Q00717, Q29387, Q3SZV3, Q4R7H5, Q4WB03, Q5Z627, Q68FR6, Q6PE25, Q6YW46, Q90YC0, Q9D8N0, Q9FUM1, Q9VG98, Q9ZRI7, S0EHD0, W7MMJ0, A0A1W2PR19, O76483, O77473, P20135, P30711, P30713, P46430, P57108, Q01579, Q03425

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1066 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23957753:AG:A	donor_gain	1.0000
22:23957929:CCGG:C	acceptor_gain	1.0000
22:23957930:CGGC:C	acceptor_gain	1.0000
22:23958454:AACAC:A	acceptor_gain	1.0000
22:23958455:ACAC:A	acceptor_gain	1.0000
22:23958456:CAC:C	acceptor_gain	1.0000
22:23958456:CACC:C	acceptor_gain	1.0000
22:23958457:ACC:A	acceptor_loss	1.0000
22:23958458:CCT:C	acceptor_loss	1.0000
22:23958459:C:CC	acceptor_gain	1.0000
22:23958459:CTGAT:C	acceptor_loss	1.0000
22:23958460:T:C	acceptor_loss	1.0000
22:23958462:A:AC	acceptor_gain	1.0000
22:23958547:TCAC:T	donor_loss	1.0000
22:23958548:CACCT:C	donor_loss	1.0000
22:23958697:CCGAG:C	acceptor_gain	1.0000
22:23958698:CGAG:C	acceptor_gain	1.0000
22:23958698:CGAGC:C	acceptor_gain	1.0000
22:23958700:AG:A	acceptor_gain	1.0000
22:23958700:AGCT:A	acceptor_loss	1.0000
22:23958702:C:CA	acceptor_loss	1.0000
22:23958702:C:CC	acceptor_gain	1.0000
22:23958872:T:TA	donor_gain	1.0000
22:23960318:T:A	donor_gain	1.0000
22:23960377:CTGCC:C	acceptor_gain	1.0000
22:23960378:TGCC:T	acceptor_gain	1.0000
22:23960380:CC:C	acceptor_gain	1.0000
22:23960381:CC:C	acceptor_gain	1.0000
22:23960382:C:CC	acceptor_gain	1.0000
22:23961015:CCCA:C	donor_loss	1.0000

AlphaMissense

1574 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23958342:G:C	F156L	0.978
22:23958342:G:T	F156L	0.978
22:23958344:A:G	F156L	0.978
22:23961089:G:T	R15S	0.969
22:23961090:G:C	S14R	0.963
22:23961090:G:T	S14R	0.963
22:23961092:T:G	S14R	0.963
22:23958652:A:G	W84R	0.961
22:23958652:A:T	W84R	0.961
22:23958701:G:C	S67R	0.961
22:23958701:G:T	S67R	0.961
22:23960295:T:G	S67R	0.961
22:23960359:G:C	F45L	0.961
22:23960359:G:T	F45L	0.961
22:23960361:A:G	F45L	0.961
22:23958360:G:C	F150L	0.959
22:23958360:G:T	F150L	0.959
22:23958362:A:G	F150L	0.959
22:23961088:C:G	R15P	0.958
22:23957879:C:A	W193C	0.948
22:23957879:C:G	W193C	0.948
22:23957881:A:G	W193R	0.945
22:23957881:A:T	W193R	0.945
22:23961070:G:T	A21D	0.945
22:23960303:A:G	L64S	0.944
22:23958601:A:G	W101R	0.943
22:23958601:A:T	W101R	0.943
22:23958313:T:A	D166V	0.940
22:23961055:A:G	I26T	0.939
22:23960347:G:C	N49K	0.938

dbSNP variants (sampled 300 via entrez): RS1003287663 (22:23958251 G>A), RS1003626883 (22:23957892 C>T), RS1006732496 (22:23959350 C>T), RS1007215800 (22:23959966 C>T), RS1007761328 (22:23957135 C>G), RS1017654543 (22:23958925 T>C), RS1021931656 (22:23958622 G>A,C), RS1026501187 (22:23957663 G>C,T), RS1027636699 (22:23959682 A>G), RS1027708348 (22:23960026 G>A), RS1029936962 (22:23958809 G>C), RS1033793744 (22:23958267 C>A), RS1037866466 (22:23957140 C>G,T), RS1037897466 (22:23958093 G>T), RS1039545819 (22:23959970 TCTC>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001277_19	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-09
GCST90011898_167	Alanine aminotransferase levels	2.000000e-09
GCST90011900_16	Serum alkaline phosphatase levels	8.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	1
Acetylglucosamine	increases expression	1
Ivermectin	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TB	Abcam HeLa GSTT2B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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