GSTO2

Summary

GSTO2 (glutathione S-transferase omega 2, HGNC:23064) is a protein-coding gene on chromosome 10q25.1, encoding Glutathione S-transferase omega-2 (Q9H4Y5). Exhibits glutathione-dependent thiol transferase activity.

The protein encoded by this gene is an omega class glutathione S-transferase (GST). GSTs are involved in the metabolism of xenobiotics and carcinogens. Four transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 119391 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 35 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.24 (unconstrained)
• MANE Select transcript: NM_183239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23064
Approved symbol	GSTO2
Name	glutathione S-transferase omega 2
Location	10q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000065621
Ensembl biotype	protein_coding
OMIM	612314
Entrez	119391

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000338595

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 3, TSL 5: 1

ENST00000338595, ENST00000369707, ENST00000450629, ENST00000467629, ENST00000473401, ENST00000477078, ENST00000498052, ENST00000912037, ENST00000912038, ENST00000912039, ENST00001119643, ENST00001129040, ENST00001136395

RefSeq mRNA: 4 — MANE Select: NM_183239 NM_001191013, NM_001191014, NM_001191015, NM_183239

CCDS: CCDS53574, CCDS53575, CCDS7556

Canonical transcript exons

ENST00000338595 — 7 exons

Exon	Start	End
ENSE00001388955	104274685	104274949
ENSE00001601180	104275226	104275334
ENSE00003327182	104269184	104269269
ENSE00003632446	104299128	104304950
ENSE00003654920	104297578	104297684
ENSE00003666141	104277894	104278116
ENSE00003674529	104279370	104279471

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 93.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8268 / max 136.3565, expressed in 1278 samples.

Highest expression (Bgee): body of pancreas, upper arm skin, pancreas, islet of Langerhans, skin of abdomen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GSTO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 80 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	4.8e-114	-0.99	10:104279427:A:G
Skin Sun Exposed Lower leg	eqtl	2.1e-110	+0.52	10:104275555:C:G
Skin Not Sun Exposed Suprapubic	sqtl	6.6e-100	-1.06	10:104279427:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.8e-96	+0.60	10:104273681:T:C
Thyroid	sqtl	6.4e-73	-1.00	10:104275555:C:G
Esophagus Mucosa	sqtl	9.5e-72	-1.03	10:104279427:A:G
Testis	sqtl	2.7e-59	-0.77	10:104273681:T:C
Pancreas	sqtl	3.4e-57	-1.14	10:104279427:A:G
Pituitary	sqtl	7.0e-54	-1.17	10:104273681:T:C
Brain Cerebellar Hemisphere	eqtl	1.2e-47	-0.95	10:104275555:C:G
Brain Cerebellum	eqtl	5.9e-47	-0.98	10:104275555:C:G
Brain Anterior cingulate cortex BA24	eqtl	9.6e-38	-0.79	10:104273681:T:C
Brain Frontal Cortex BA9	eqtl	8.3e-37	-0.85	10:104275555:C:G
Artery Aorta	sqtl	4.2e-36	-0.90	10:104275555:C:G
Nerve Tibial	eqtl	7.5e-36	-0.44	10:104275555:C:G
Brain Caudate basal ganglia	sqtl	2.9e-35	-1.11	10:104273681:T:C
Brain Nucleus accumbens basal ganglia	sqtl	7.9e-35	-1.08	10:104275555:C:G
Brain Cortex	eqtl	4.2e-33	-0.83	10:104275555:C:G
Cells Cultured fibroblasts	eqtl	1.8e-29	+1.64	10:104267428:A:T
Brain Caudate basal ganglia	eqtl	9.5e-29	-0.42	10:104275555:C:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
106883	6.5846	1005
106882	3.9498	766
106880	1.1455	711
106881	0.0781	21
106879	0.0446	3
106878	0.0242	9

Top tissues by expression

showing 100 of 247 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	93.05	gold quality
upper arm skin	UBERON:0004263	92.41	gold quality
pancreas	UBERON:0001264	91.37	gold quality
islet of Langerhans	UBERON:0000006	91.29	gold quality
skin of abdomen	UBERON:0001416	91.26	gold quality
right testis	UBERON:0004534	91.22	gold quality
right uterine tube	UBERON:0001302	91.11	gold quality
left testis	UBERON:0004533	91.04	gold quality
skin of leg	UBERON:0001511	90.59	gold quality
adenohypophysis	UBERON:0002196	90.49	gold quality
pituitary gland	UBERON:0000007	90.18	gold quality
zone of skin	UBERON:0000014	89.98	gold quality
testis	UBERON:0000473	88.69	gold quality
pancreatic ductal cell	CL:0002079	88.20	silver quality
ileal mucosa	UBERON:0000331	87.91	gold quality
upper leg skin	UBERON:0004262	87.44	gold quality
sperm	CL:0000019	87.33	gold quality
esophagus mucosa	UBERON:0002469	86.98	gold quality
metanephros cortex	UBERON:0010533	86.27	gold quality
corpus epididymis	UBERON:0004359	86.11	gold quality
right lobe of thyroid gland	UBERON:0001119	85.99	gold quality
left lobe of thyroid gland	UBERON:0001120	85.73	gold quality
thyroid gland	UBERON:0002046	85.54	gold quality
mucosa of transverse colon	UBERON:0004991	85.17	gold quality
prostate gland	UBERON:0002367	85.00	gold quality
minor salivary gland	UBERON:0001830	84.95	gold quality
adult organism	UBERON:0007023	84.85	gold quality
rectum	UBERON:0001052	84.57	gold quality
mouth mucosa	UBERON:0003729	84.26	gold quality
skin of hip	UBERON:0001554	84.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.91	gold quality
body of stomach	UBERON:0001161	83.83	gold quality
lower esophagus mucosa	UBERON:0035834	83.81	gold quality
adult mammalian kidney	UBERON:0000082	83.63	gold quality
oviduct epithelium	UBERON:0004804	83.60	gold quality
saliva-secreting gland	UBERON:0001044	83.44	gold quality
pigmented layer of retina	UBERON:0001782	83.21	gold quality
cortex of kidney	UBERON:0001225	82.45	gold quality
nucleus accumbens	UBERON:0001882	82.44	gold quality
stomach	UBERON:0000945	82.34	gold quality
duodenum	UBERON:0002114	82.18	gold quality
metanephros	UBERON:0000081	81.94	gold quality
vagina	UBERON:0000996	81.76	gold quality
kidney	UBERON:0002113	81.76	gold quality
esophagus squamous epithelium	UBERON:0006920	81.64	gold quality
gingival epithelium	UBERON:0001949	81.60	gold quality
left ovary	UBERON:0002119	81.56	gold quality
bronchial epithelial cell	CL:0002328	81.46	gold quality
seminal vesicle	UBERON:0000998	81.27	gold quality
caudate nucleus	UBERON:0001873	81.22	gold quality
gingiva	UBERON:0001828	81.05	gold quality
prefrontal cortex	UBERON:0000451	80.70	gold quality
putamen	UBERON:0001874	80.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.60	gold quality
bronchus	UBERON:0002185	80.52	gold quality
fallopian tube	UBERON:0003889	80.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.83	gold quality
ventricular zone	UBERON:0003053	79.13	gold quality
endometrium	UBERON:0001295	79.10	gold quality
ovary	UBERON:0000992	79.03	gold quality
anterior cingulate cortex	UBERON:0009835	79.02	gold quality
transverse colon	UBERON:0001157	78.62	gold quality
oral cavity	UBERON:0000167	78.53	gold quality
kidney epithelium	UBERON:0004819	78.32	silver quality
mammalian vulva	UBERON:0000997	78.15	gold quality
hypothalamus	UBERON:0001898	78.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.92	gold quality
amygdala	UBERON:0001876	77.72	gold quality
forebrain	UBERON:0001890	77.51	gold quality
right frontal lobe	UBERON:0002810	77.48	gold quality
caput epididymis	UBERON:0004358	77.42	gold quality
jejunal mucosa	UBERON:0000399	77.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.34	gold quality
colonic mucosa	UBERON:0000317	77.03	gold quality
cauda epididymis	UBERON:0004360	76.91	gold quality
right ovary	UBERON:0002118	76.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.89	gold quality
neocortex	UBERON:0001950	76.80	gold quality
frontal cortex	UBERON:0001870	76.71	gold quality
right adrenal gland	UBERON:0001233	76.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.33	gold quality
small intestine	UBERON:0002108	76.14	gold quality
adrenal tissue	UBERON:0018303	76.14	gold quality
stromal cell of endometrium	CL:0002255	76.05	gold quality
ganglionic eminence	UBERON:0004023	75.95	gold quality
left adrenal gland cortex	UBERON:0035825	75.95	gold quality
right adrenal gland cortex	UBERON:0035827	75.87	gold quality
nipple	UBERON:0002030	75.78	gold quality
brain	UBERON:0000955	75.75	gold quality
amniotic fluid	UBERON:0000173	75.69	gold quality
esophagus	UBERON:0001043	75.64	gold quality
female reproductive system	UBERON:0000474	75.35	gold quality
descending thoracic aorta	UBERON:0002345	75.31	gold quality
left adrenal gland	UBERON:0001234	75.29	gold quality
cerebral cortex	UBERON:0000956	75.15	gold quality
adrenal cortex	UBERON:0001235	74.76	gold quality
adrenal gland	UBERON:0002369	74.75	gold quality
epithelium of mammary gland	UBERON:0003244	74.68	gold quality
tonsil	UBERON:0002372	74.56	gold quality
mammary duct	UBERON:0001765	74.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.36

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	20.8
Postcentral gyrus	tissue	17.5
Hippocampus	tissue	14.2	low
Locus coeruleus	tissue	13.4
Pituitary gland	tissue	9.8
Choroid plexus	tissue	9.6
Testis	tissue	9.3	medium
Skin 1	tissue	6.2	low
Retina	tissue	5.6
Pancreas	tissue	5.3	medium
Breast	tissue	4.9	medium
Stomach 1	tissue	4.9	medium
Parathyroid gland	tissue	4.7	medium
Epididymis	tissue	4.6	high
Fallopian tube	tissue	4.1	high
Prostate	tissue	4.0	high
Kidney	tissue	3.9	medium
Thyroid gland	tissue	3.8	medium
Vagina	tissue	3.3	medium
Seminal vesicle	tissue	3.0	medium
Rectum	tissue	2.9	medium
Cerebellum	tissue	2.8	not detected
Cervix	tissue	2.7	high
Colon	tissue	2.7	medium
Small intestine	tissue	2.7	medium
Duodenum	tissue	2.7	medium
Ovary	tissue	2.6	not detected
Salivary gland	tissue	2.5	medium
Esophagus	tissue	2.3	low
Endometrium 1	tissue	2.1	high
Thymus	tissue	2.0
Bone marrow	tissue	1.9	medium
Olfactory bulb	tissue	1.7
Adrenal gland	tissue	1.6	medium
Prefrontal cortex	tissue	1.5
Cerebral cortex	tissue	1.5	low
Urinary bladder	tissue	1.5	medium
Retrosplenial and cingulate cortex	tissue	1.5
Insular cortex	tissue	1.5
Amygdala	tissue	1.4
Skeletal muscle	tissue	1.3	not detected
Motor cortex	tissue	1.3
Lung	tissue	1.3	medium
Liver	tissue	1.3	medium
Hippocampal formation	tissue	1.3
Retrosplenial cortex	tissue	1.3
Tongue	tissue	1.2
Frontal cortex	tissue	1.2
Gallbladder	tissue	1.2	high
Spinal cord	tissue	1.2
Corpus callosum	tissue	1.2
Entorhinal cortex	tissue	1.2
Caudate putamen	tissue	1.2
Somatosensory cortex	tissue	1.2
Temporal cortex	tissue	1.2
Smooth muscle	tissue	1.1	medium
Basal ganglia	tissue	1.1	low
Putamen	tissue	1.1
Medulla oblongata	tissue	1.1
Superior colliculi	tissue	1.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior insular cortex (19.5), Parieto-temporal junction (white matter) (19.4), Stria terminalis, bed nucleus (19.3), Caudate nucleus (19.2), Transversal temporal gyrus, posterior (19.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GSTO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

12 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-2277-3P	91.94	62.27	299

Functional genomics

gnomAD constraint: pLI 1.03e-05, LOEUF 1.24, missense Z 0.236 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000338595 — one region, missense o/e 1.00.

Literature-anchored findings (GeneRIF, showing 40)

• Our results do not confirm an association between PD and frequency of the polymorphisms investigated: hGSTO1*A140D, & hGSTO1*E155del. (PMID:15159516)
• no association either with age-at-onset in AD cases or with disease risk in the case-control cohort but haplotype analysis revealed a modest association of one haplotype with AD risk (p = 0.04) (PMID:15917099)
• molecular cloning; GSTO2 was ubiquitously expressed at a low level, with a higher expression in pancreas and prostate (PMID:15942673)
• a glutathione S-transferase omega 2 gene polymorphism may havea role in ovarian cancer (PMID:16761626)
• Differences in expression at the protein level of the major splice variant of GSTO2 suggests that this enzyme is less active in human cells compared with chimpanzee cells. (PMID:17978102)
• GSTO2 DD genotype was associated with decreased risk as compared to GSTO2 NN genotype (OR = 0.21, 95% CI: 0.05-0.92, P = 0.038) (PMID:18398695)
• These results suggest a possible effect of the GSTO1 and 2 locus on age of onset of FALS. (PMID:18427999)
• GSTO1*A140D polymorphism is significantly associated with susceptibility to childhood acute lymphoblastic leukemia. (PMID:18941778)
• Report GSTO2 gene polymorphisms in worldwide populations. (PMID:18986335)
• The genetic polymorphism of GSTT1, GSTM1 and GSTO2 N412D in three Iranian populations was detected. (PMID:19430957)
• The Asn142Asp polymorphism in GSTO2 and the GSTO1-140Asp/GSTO2-142Asp haplotype were associated with increased risk of COPD. GSTO2 is a candidate gene for COPD, but is not associated with FEV(1). (PMID:19513904)
• polymorphisms in GSTO1 or GSTO2 do not appear to contribute to the large individual variability in arsenic metabolism or susceptibility to arsenicosis. (PMID:19635583)
• Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma was found. (PMID:19686770)
• Genetic polymorphisms in GSTM1, GSTO2, XRCC1 at codons 194 and 399 may act additively for developing breast cancer (PMID:19731014)
• it is unlikely that glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 participate in breast cancer susceptibility. (PMID:19859803)
• 142Asp allozyme could modulate arsenic biotransformation and thereby arsenic toxicity (PMID:20045512)
• This study provides the allele frequencies of GSTO polymorphism in a sample consisting of 116 apparently healthy individuals of both sexes from Rome (Central Italy). (PMID:20113212)
• the frequencies of GSTA1 (glutathione S-transferase alpha 1), GSTM1(GST mu 1 ), GSTO2(GST omega 2) and GSTT1(GST theta 1) genotypes found in asthmatic patients differ from those of controls (PMID:20367187)
• Subjects who had the GSTO2 homozygous D142 genotype were found to have an increased risk of asthma (PMID:20374258)
• Has a role in the risk of Urothelial carcinogenesis (PMID:21094982)
• GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives. (PMID:21113667)
• CYP2D6 (rs16947) and GSTO2 (rs156697) polymorphisms are independent factors influencing complete remission rates of the first induction chemotherapy in de novo AML patients. (PMID:21518482)
• GSTA1 and the GSTO2 are asthma susceptible genes involved in increasing the risk of asthma development in the Italian population (PMID:22040239)
• Found that rs156697 minor allele of GSTO2 associates with increased risk in the older ADs with age-at-diagnosis > 80 years. The minor alleles of GSTO1 rs4925 and GSTO2 rs156697 associate with lower brain levels of GSTO2, but not GSTO1. (PMID:22494505)
• crystal structures of human GSTO2-2, stabilized through site-directed mutagenesis and determined at 1.9 A resolution in the presence and absence of glutathione (PMID:22522127)
• The polymorphisms of GSTM1 and GSTO2 along with the work place influence may act additively for developing cataract. (PMID:22876127)
• Variants in human GSTO2 could increase disease risk susceptibility and could act as a risk factor for hypothyroidism in Italian patients. (PMID:23079717)
• The frequencies of GSTO1 and GSTO2 genotypes were not significantly different between head and neck squamous cell carcinoma cases and controls. (PMID:23086268)
• No significant association between GSTO2 polymorphism and acute renal graft rejection. (PMID:23649768)
• The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects, suggesting a role of inefficient ascorbate regeneration in cataract development. (PMID:23927022)
• GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer. (PMID:24040330)
• The GSTA1*-69T and GSTO2*D142 variants are both associated with a significantly increased risk of asthma. (PMID:24471578)
• The present study found that rs3740400 in As3MT and rs156697 in GSTO2 were strongly associated with the arsenic species (%iAs, %MMA and MMA/iAs and DMA/MMA ratios) in urine of the occupationally exposed workers and they may influence methylation capacity. (PMID:25491248)
• Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking. (PMID:25716313)
• No significant association has been found between childhood Pre-B acute lymphoblastic leukemia and GSTO1 A140D and GSTO2 N142D polymorphisms. (PMID:25726706)
• we for the first time provided evidence supporting the prognostic role of GSTO2 in the progression of TACE-treated hepatocellular carcinoma (PMID:25835968)
• GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for hepatocellular carcinoma patients. (PMID:25892883)
• GSTO2 genetic polymorphisms are not associated with the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. (PMID:26103006)
• GSTO2 genetic polymorphisms are associated with the progression of HBV infection. (PMID:27221910)
• The GSTO2 rs2297235 “AG” genotype is associated to SCA2 but failed to show any association with clinical markers, with the exception of a potential association with the age at disease onset. (PMID:28017238)

Cross-species orthologs

42 orthologs

Organism	Symbol	Gene ID
danio_rerio	gstr	ENSDARG00000042620
danio_rerio	gstt2	ENSDARG00000095464
mus_musculus	Gsto2	ENSMUSG00000025069
rattus_norvegicus	Gsto2	ENSRNOG00000069697
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): GSTT2 (ENSG00000099984), GSTZ1 (ENSG00000100577), GDAP1 (ENSG00000104381), CLIC5 (ENSG00000112782), GDAP1L1 (ENSG00000124194), GSTT2B (ENSG00000133433), GSTO1 (ENSG00000148834), CLIC2 (ENSG00000155962), CLIC6 (ENSG00000159212), CLIC4 (ENSG00000169504), CLIC3 (ENSG00000169583), CLIC1 (ENSG00000213719), EEF1G (ENSG00000254772), GSTT4 (ENSG00000276950)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915464) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased bone mineral density	1
abnormal vibrissa morphology	1
increased heart weight	1
increased bone mineral content	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Nicotiana tabacum	Q03663	94.2%	Diamond
Sus scrofa	Q9N1F5	81.7%	Diamond
Solanum tuberosum	P32111	75.2%	Diamond
Caenorhabditis briggsae	A8XT16	65.4%	Diamond
Glycine max	P32110	56.0%	Diamond
Aplysia californica	P81124	41.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ITPRIP-AS1	ncRNA	101927472
LINC02620	ncRNA	101927523
CFAP58	protein-coding	159686
ITPRIP	protein-coding	85450
MIR609	ncRNA	693194
CFAP43	protein-coding	80217
GSTO1	protein-coding	9446
CFAP58-DT	ncRNA	100505869
MIR4482	ncRNA	100616323

Protein

Protein identifiers

Glutathione S-transferase omega-2 — Q9H4Y5 (reviewed: Q9H4Y5)

Alternative names: Glutathione S-transferase omega 2-2, Glutathione-dependent dehydroascorbate reductase, Monomethylarsonic acid reductase

All UniProt accessions (1): Q9H4Y5

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).

Tissue specificity. Expressed in a range of tissues, including the liver, kidney, skeletal muscle and prostate. Strongest expression in the testis.

Similarity. Belongs to the GST superfamily. Omega family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H4Y5-1	1	yes
Q9H4Y5-2	2
Q9H4Y5-3	3

RefSeq proteins (4): NP_001177942, NP_001177943, NP_001177944, NP_899062* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004045	Glutathione_S-Trfase_N	Domain
IPR005442	GST_omega	Family
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
IPR050983	GST_Omega/HSP26	Family

Pfam: PF13417

Enzyme classification (BRENDA)

• EC 1.8.5.1 — glutathione dehydrogenase (ascorbate) (BRENDA: 48 organisms, 27 substrates, 37 inhibitors, 140 Km, 68 kcat entries)
• EC 2.5.1.18 — glutathione transferase (BRENDA: 178 organisms, 548 substrates, 680 inhibitors, 878 Km, 525 kcat entries)

Substrate kinetics (BRENDA)

82 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
DEHYDROASCORBATE	0.019–2.5	73
GSH	0.0003–37.4	62
GLUTATHIONE	0.04–12.71	42
REDUCED GLUTATHIONE	0.017–11.4	24
ETHACRYNIC ACID	0.0001–2.43	19
GSH	0.69–5.2	17
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

Catalyzed reactions (Rhea)

• methylarsonate + 2 glutathione + H(+) = methylarsonous acid + glutathione disulfide + H2O (RHEA:15969)
• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)
• L-dehydroascorbate + 2 glutathione = glutathione disulfide + L-ascorbate (RHEA:24424)

UniProt features (36 total): helix 16, strand 6, binding site 3, domain 2, sequence variant 2, splice variant 2, chain 1, mutagenesis site 1, sequence conflict 1, turn 1, active site 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
3Q18	Human Glutathione Transferase O2	X-RAY DIFFRACTION	1.7
3Q19	Human Glutathione Transferase O2	X-RAY DIFFRACTION	1.9
3QAG	Human Glutathione Transferase O2 with glutathione -new crystal form	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4Y5-F1	97.33	0.98

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
32	nucleophile

Ligand- & substrate-binding residues (3)

Position	Role
59	glutathione
72	glutathione
85–86	glutathione

Mutagenesis-validated functional residues (1)

Position	Phenotype
34	abolishes dhar activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-211859	Biological oxidations	—
R-HSA-156590	Glutathione conjugation	—
R-HSA-1430728	Metabolism	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	—
R-HSA-156580	Phase II - Conjugation of compounds	—
R-HSA-196836	Vitamin C (ascorbate) metabolism	—

MSigDB gene sets: 95 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, TGACCTY_ERR1_Q2, CHANDRAN_METASTASIS_DN, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, YGACNNYACAR_UNKNOWN, GOBP_L_ASCORBIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_ARSENIC_CONTAINING_SUBSTANCE, GOBP_DETOXIFICATION, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, REACTOME_GLUTATHIONE_CONJUGATION, GOBP_GLUTATHIONE_METABOLIC_PROCESS

GO Biological Process (5): glutathione metabolic process (GO:0006749), xenobiotic metabolic process (GO:0006805), L-ascorbic acid metabolic process (GO:0019852), cellular response to arsenic-containing substance (GO:0071243), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (7): glutathione transferase activity (GO:0004364), oxidoreductase activity (GO:0016491), identical protein binding (GO:0042802), glutathione dehydrogenase (ascorbate) activity (GO:0045174), methylarsonate reductase activity (GO:0050610), 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

5 top-level categories:

Category	Pathways
Metabolism	2
Phase II - Conjugation of compounds	1
Metabolism of water-soluble vitamins and cofactors	1
Biological oxidations	1
Metabolism of vitamins and cofactors	1

GO top-level categories

22 GO namespaces:

Category	Terms
catalytic activity	2
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
monosaccharide metabolic process	1
carboxylic acid metabolic process	1
lactone metabolic process	1
response to arsenic-containing substance	1
cellular response to chemical stimulus	1
cellular detoxification	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein binding	1
glutathione disulfide oxidoreductase activity	1
antioxidant activity	1
oxidoreductase activity, acting on a sulfur group of donors, quinone or similar compound as acceptor	1
oxidoreductase activity, acting on phosphorus or arsenic in donors, disulfide as acceptor	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
L-ascorbic acid metabolic process	BP	direct assay
cellular response to arsenic-containing substance	BP	direct assay
xenobiotic metabolic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
glutathione dehydrogenase (ascorbate) activity	MF	direct assay
identical protein binding	MF	physical interaction
oxidoreductase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,410 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSTO2	HPGDS	O60760	793
GSTO2	GLRX	P35754	681
GSTO2	GSTP1	P09211	660
GSTO2	GSTM1	P09488	647
GSTO2	SLCO6A1	Q86UG4	639
GSTO2	GSTA1	P08263	628
GSTO2	AS3MT	Q9HBK9	593
GSTO2	GSTT2B	P0CG30	572
GSTO2	MGST1	P10620	570
GSTO2	GSTK1	Q9Y2Q3	567
GSTO2	GSTM5	P46439	562
GSTO2	GSTM2	P28161	542
GSTO2	GSTA3	Q16772	537
GSTO2	GSTM3	P21266	529
GSTO2	CYP46A1	Q9Y6A2	488

IntAct

Human interaction partners of GSTO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
TFAP2A	physical association	0.720	10
GCA	physical association	0.560	3
HOXC8	physical association	0.560	3
INCA1	physical association	0.560	3
KLHL10	physical association	0.560	3
MUM1	physical association	0.560	3
NTAQ1	physical association	0.560	3
PFDN5	physical association	0.560	3
POLR1C	physical association	0.560	3
SMARCC1	physical association	0.560	3
SAV1	physical association	0.370	1
GPX4	association	0.350	1
GSTO1	association	0.350	1

BioGRID (35 interactions; top human partners by supporting records): TFAP2A (Two-hybrid; 3 records), C10orf88 (Affinity Capture-MS; 2 records), EDRF1 (Affinity Capture-MS; 2 records), RBM12 (Affinity Capture-MS; 2 records), AGO2 (Affinity Capture-RNA), CNDP2 (Co-fractionation), CREBBP (Two-hybrid), FKBP1A (Co-fractionation), GCA (Two-hybrid), GPX4 (Affinity Capture-MS), GSTO1 (Affinity Capture-MS), HINT1 (Co-fractionation), HOXC8 (Two-hybrid), INCA1 (Two-hybrid), IQCF5 (Cross-Linking-MS (XL-MS))

Disease & clinical

Genetic variants

Variant evidence for GSTO2: 37 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 736):

Position(s)	Effect	Δscore	Sites
10:104269303	donor_gain	1.0000
10:104275212–104275213	acceptor_gain	1.0000	2
10:104277883	acceptor_gain	1.0000
10:104277892	acceptor_gain	1.0000
10:104275216	acceptor_gain	0.9900
10:104275224–104275225	acceptor_loss	0.9900	6
10:104275335–104275336	donor_loss	0.9900	5
10:104277892–104277893	acceptor_loss	0.9900	4
10:104269270–104269271	donor_loss	0.9800	5
10:104277893	acceptor_loss	0.9800

AlphaMissense

460 missense substitutions predicted likely pathogenic (of 1,601 scored), across 133 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D175	8	0.929	0.956
W62	7	0.942	0.989
F31	7	0.924	0.984
F226	7	0.887	0.983
W203	7	0.882	0.954
W179	7	0.873	0.976
R37	7	0.863	0.966
W181	7	0.839	0.970
F165	7	0.815	0.969
C32	7	0.814	0.956
D239	7	0.786	0.850
K45	6	0.934	0.979
E76	6	0.885	0.941
P180	6	0.841	0.935
P73	6	0.832	0.931
P60	6	0.826	0.941
M207	6	0.816	0.866
E183	6	0.790	0.861
M29	6	0.779	0.933
K59	6	0.777	0.954

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	9.01e-05

Disease associations

OMIM: gene MIM:612314 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST012489_83	Heel bone mineral density x serum urate levels interaction	4e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2161 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases expression, affects metabolic processing, affects reaction, affects response to substance, increases metabolic processing (+3 more)	8
sodium arsenite	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenate	increases abundance, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
flutriafol	decreases reaction, increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	increases abundance, increases expression	1
Acetylcysteine	increases expression, decreases reaction	1
Amiodarone	increases expression	1
Cacodylic Acid	affects abundance, affects metabolic processing	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Environmental Pollutants	affects response to substance	1
Estradiol	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743233	ADMET	Substrates for human cytosolic glutathione transferase GSTO2	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.