GPX1

Summary

GPX1 (glutathione peroxidase 1, HGNC:4553) is a protein-coding gene on chromosome 3p21.31, encoding Glutathione peroxidase 1 (P07203). Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis.

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Other studies indicate that H2O2 is also essential for growth-factor mediated signal transduction, mitochondrial function, and maintenance of thiol redox-balance; therefore, by limiting H2O2 accumulation, glutathione peroxidases are also involved in modulating these processes. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is the most abundant, is ubiquitously expressed and localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. It is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. This gene contains an in-frame GCG trinucleotide repeat in the coding region, and three alleles with 4, 5 or 6 repeats have been found in the human population. The allele with 4 GCG repeats has been significantly associated with breast cancer risk in premenopausal women. Alternatively spliced transcript variants have been found for this gene. Pseudogenes of this locus have been identified on chromosomes X and 21.

Source: NCBI Gene 2876 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gluthathione peroxidase deficiency (Limited, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 66 total
• Phenotypes (HPO): 4
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4553
Approved symbol	GPX1
Name	glutathione peroxidase 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000233276
Ensembl biotype	protein_coding
OMIM	138320
Entrez	2876

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 nonsense_mediated_decay

ENST00000419349, ENST00000419783, ENST00000496791, ENST00000643797, ENST00000646881, ENST00000703795, ENST00000703796, ENST00000703797, ENST00000704356, ENST00000704374, ENST00000704375, ENST00000704376, ENST00000704377, ENST00000704378

RefSeq mRNA: 5 — MANE Select: NM_000581 NM_000581, NM_001329455, NM_001329502, NM_001329503, NM_201397

CCDS: CCDS43091, CCDS54582, CCDS87077, CCDS87078, CCDS87079

Canonical transcript exons

ENST00000419783 — 2 exons

Exon	Start	End
ENSE00003989945	49357176	49357747
ENSE00003991546	49358027	49358353

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1659 / max 269.4716, expressed in 1660 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42246	16.5683	1647
42244	9.0148	1556
42245	5.0465	1555
42241	1.3689	731
42242	0.5717	223
42243	0.4823	287
42247	0.1133	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.69	gold quality
leukocyte	CL:0000738	99.66	gold quality
granulocyte	CL:0000094	99.47	gold quality
blood	UBERON:0000178	99.47	gold quality
right adrenal gland	UBERON:0001233	99.42	gold quality
left adrenal gland cortex	UBERON:0035825	99.41	gold quality
right adrenal gland cortex	UBERON:0035827	99.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.40	gold quality
left adrenal gland	UBERON:0001234	99.39	gold quality
right lung	UBERON:0002167	99.33	gold quality
spleen	UBERON:0002106	99.28	gold quality
omental fat pad	UBERON:0010414	99.27	gold quality
adipose tissue	UBERON:0001013	99.21	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.18	gold quality
right lobe of liver	UBERON:0001114	99.09	gold quality
metanephros cortex	UBERON:0010533	99.09	gold quality
upper lobe of left lung	UBERON:0008952	99.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.06	gold quality
left coronary artery	UBERON:0001626	98.99	gold quality
mucosa of stomach	UBERON:0001199	98.90	gold quality
right coronary artery	UBERON:0001625	98.89	gold quality
endocervix	UBERON:0000458	98.86	gold quality
adult mammalian kidney	UBERON:0000082	98.83	gold quality
adrenal gland	UBERON:0002369	98.80	gold quality
esophagus mucosa	UBERON:0002469	98.80	gold quality
cortex of kidney	UBERON:0001225	98.79	gold quality
descending thoracic aorta	UBERON:0002345	98.79	gold quality
placenta	UBERON:0001987	98.78	gold quality
prostate gland	UBERON:0002367	98.78	gold quality
ectocervix	UBERON:0012249	98.74	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 40.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	18897.03
E-MTAB-10432	yes	14896.80
E-MTAB-9221	yes	14317.64
E-CURD-122	yes	14293.42
E-MTAB-8207	yes	11297.22
E-HCAD-4	yes	9472.05
E-HCAD-10	yes	6015.53
E-CURD-98	yes	5313.06
E-GEOD-135922	yes	4980.26
E-GEOD-134144	yes	4950.59
E-MTAB-8495	yes	4435.33
E-HCAD-9	yes	3766.17
E-MTAB-10042	yes	3164.26
E-MTAB-6701	yes	2797.39
E-CURD-120	yes	2792.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A, TFAP2C, TP53

miRNA regulators (miRDB)

12 targeting GPX1, 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-1296-3P	99.72	64.04	636
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-877-5P	94.62	66.30	710
HSA-MIR-4655-3P	82.43	62.92	60

Literature-anchored findings (GeneRIF, showing 40)

• role in the inflammatory response in a model of stroke in GPX1 transgenic mice (PMID:11823528)
• protects from CD95-induced apoptosis in cultured breast cancer cells (PMID:12221075)
• Malignant lung tumors (squamous cell carcinoma and adenocarcinoma) had significantly increased levels of this enzyme. (PMID:12447480)
• Results indicate that glutathione peroxidase 1-sensitive reactive oxygen species play an important role in regulation of cell death during cerebral ischemia-reperfusion as well as in brain inflammatory reactions. (PMID:12531513)
• A characteristic polyalanine sequence polymorphism in exon 1 of hgpx1 produces three alleles with five, six or seven alanine (ALA) repeats in this sequence. (PMID:12655278)
• GPx-1 activity condition can downregulate basal 20S proteasome activity (PMID:12751788)
• GPX1 was measured in the blood from patients with diabetes mellitus, insulin-dependent. (PMID:12787913)
• The GPx-1 Leu-containing codon 198 allele was more frequently seen in breast cancer than the Pro-containing one. LOH at this locus occurred in ~36% of the breast tumors. GPx-1 allelic identity & LOH have a role as factors in breast cancer development. (PMID:12810669)
• GPX1 overexpression delays cell growth and protects them from GSH and H(2)O(2) toxicity (PMID:12829378)
• PU.1 directly regulated the expression of only the glutathione peroxidase gene through binding sites in the promoter and a 3’ regulatory region. (PMID:12832449)
• c-Abl and Arg associate with glutathione peroxidase 1 (GPx1), and this interaction is regulated by intracellular oxidant levels. The c-Abl and Arg SH3 domains bind directly to a proline-rich site in GPx1 at amino acids 132-145. (PMID:12893824)
• GPX1 inhibits 5-lipoxygenase in human blood cells (PMID:12893830)
• Normal pregnancy is associated with increased glutathione peroxidase activity and insulin resistance. Potential link among antioxidant defenses, insulin resistance, and dietary fat intake. (PMID:14671197)
• Genetic manipulation of islet beta cells to increase expression of Gpx-1 may protect them from oxidative injury associated with the transplantation procedure. (PMID:14962293)
• High glutathione peroxidase activity in human alveolar macrophages limits the effectiveness of H2O2 to act as a mediator of inflammatory gene expression. (PMID:14962975)
• No statistically significant differences for GPx-1, phospholipid hydroperoxide glutathione peroxidase, and glutathione reductase were encountered between normal values and those of asthenozoospermic patients. (PMID:15149466)
• Akt and P70S6K phosphorylation and Gadd45 levels are modulated by GPx-1 in tumor cells (PMID:15203190)
• The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer. (PMID:15247771)
• the immature brain has limited GPX activity and is more susceptible to oxidative damage and may explain the paradoxical effect seen in ischemic neonatal brain when SOD1 is overexpressed. (PMID:15295091)
• There is no evidence between GPX1 polymorphism and the risk of basal cell carcinoma. (PMID:15298967)
• GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia. (PMID:15318035)
• functional variants in the GPx-1 gene are associated with increased intima-media thickness of carotid arteries and risk of cardiovascular and peripheral vascular diseases in type 2 diabetic patients. (PMID:15331559)
• The functional polymorphism (Pro198Leu) in he GPX1 gene might be associated with openness to experience among the personality traits. (PMID:15990458)
• overexpressing an antioxidant gene such as GPX1 in endothelial cells is able to change the basal mRNA and protein Bax levels without affecting those of p53 and Bcl-2 (PMID:16132718)
• glutathione peroxidase-1 activity is decreased by aminoglycosides through interference with selenocysteine incorporation (PMID:16354666)
• NF-kappaB is upregulated in the Gpx1(-/-) mouse, and this upregulation contributes to the increased cell death seen in the Gpx1(-/-) after middle cerebral artery occlusion. (PMID:16627788)
• associations between several smoking variables and alcohol intake and lung cancer risk among GPX1(TT) carriers than among GPX1(CC) and GPX1(CT) carriers (PMID:16797832)
• Polymorphisms in the GPX-1 and MnSOD genes may have a role in development of breast cancer (PMID:16945136)
• We have been able to correlate embryo morphology on day 3 with the sperm expression of GPX family members. (PMID:16979635)
• Role for selenium in risk of lung cancer and independent regulation of GPX1 in a tumor cell line. (PMID:17052796)
• These findings suggest that GPx-1 inhibits UVA-induced AP-2alpha expression by suppressing the accumulation of H(2)O(2). (PMID:17097614)
• Systemic activity of the enzymatic antioxidants (CuZn/SOD, MnSOD, GSH-Px, and CAT) as well as level of lipid peroxidation determined by MDA may not be increased in the course of immune-inflammatory processes associated with chronic idiopathic urticaria. (PMID:17171548)
• the C –> T polymorphism of GPX1 genotype was independently associated with in-stent restenosis in a Japanese population (PMID:17275003)
• Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage (PMID:17625244)
• The presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in type 2 diabetes. (PMID:17825092)
• study shows the well-documented CAT exon 9 T/C & GPX 1 codon 200 polymorphisms may not be associated with Gujarat vitiligo patients; results suggest presence of novel SNPs in Gujarat vitiligo population (PMID:17850515)
• docosahexaenoic acid sensitizes breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response (PMID:18267129)
• T-Allel of GPX1(Pro200Leu)plays a protective role in early onset lung cancer susceptibility (PMID:18298806)
• found a positive association between the studied GPX1 polymorphism and lobar PICH in a Polish population. (PMID:18417962)
• No significant risk for GPX1 in colorectal adenoma. (PMID:18483336)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpx9	ENSDARG00000003077
mus_musculus	Gpx1	ENSMUSG00000063856
rattus_norvegicus	Gpx1	ENSRNOG00000048812
caenorhabditis_elegans		WBGENE00007516
caenorhabditis_elegans		WBGENE00007517
caenorhabditis_elegans		WBGENE00011045
caenorhabditis_elegans	gpx-8	WBGENE00018850
caenorhabditis_elegans		WBGENE00022377

Paralogs (7): GPX7 (ENSG00000116157), GPX8 (ENSG00000164294), GPX4 (ENSG00000167468), GPX2 (ENSG00000176153), GPX6 (ENSG00000198704), GPX3 (ENSG00000211445), GPX5 (ENSG00000224586)

Protein

Protein identifiers

Glutathione peroxidase 1 — P07203 (reviewed: P07203)

Alternative names: Cellular glutathione peroxidase, Phospholipid-hydroperoxide glutathione peroxidase GPX1

All UniProt accessions (11): P07203, A0A2R8Y6B6, A0A7I2UQ36, A0A7I2YMD7, A0A994J430, A0A994J4E2, A0A994J4K6, A0A994J4L4, A0A994J702, A0A994J707, A0A994J7E8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis. Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides. In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway.

Subunit / interactions. Homotetramer. Interacts with MIEN1.

Subcellular location. Cytoplasm. Mitochondrion.

Tissue specificity. Expressed in platelets (at protein level).

Post-translational modifications. During periods of oxidative stress, Sec-49 may react with a superoxide radical, irreversibly lose hydroselenide and be converted to dehydroalanine.

Similarity. Belongs to the glutathione peroxidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07203-1	1	yes
P07203-2	2

RefSeq proteins (5): NP_000572, NP_001316384, NP_001316431, NP_001316432, NP_958799 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000889	Glutathione_peroxidase	Family
IPR029759	GPX_AS	Active_site
IPR029760	GPX_CS	Conserved_site
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF00255

Enzyme classification (BRENDA):

• EC 1.11.1.9 — glutathione peroxidase (BRENDA: 58 organisms, 96 substrates, 65 inhibitors, 63 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
H2O2	0.0023–19.08	19
GSH	0.033–11.1	18
CUMENE HYDROPEROXIDE	0.006–7.8	6
TERT-BUTYL HYDROPEROXIDE	0.059–7.9	6
GLUTATHIONE	0.022–1.73	4
CUMENE PEROXIDE	0.09–0.42	2
L-ALPHA-PHOSPHATIDYLCHOLINE HYDROPEROXIDE	0.026–9.7	2
LINOLENIC ACID HYDROPEROXIDE	0.007–3.8	2
CHOLESTEROL 5ALPHA-HYDROPEROXIDE	0.004	1
CHOLESTEROL 7ALPHA-HYDROPEROXIDE	0.011	1
CHOLESTEROL 7BETA-HYDROPEROXIDE	0.003	1
TERT-BUTYLHYDROPEROXIDE	0.024	1

Catalyzed reactions (Rhea), 12 shown:

• 2 glutathione + H2O2 = glutathione disulfide + 2 H2O (RHEA:16833)
• a hydroperoxy polyunsaturated fatty acid + 2 glutathione = a hydroxy polyunsaturated fatty acid + glutathione disulfide + H2O (RHEA:19057)
• (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + glutathione disulfide + H2O (RHEA:48620)
• (13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O (RHEA:48888)
• (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + glutathione disulfide + H2O (RHEA:50708)
• tert-butyl hydroperoxide + 2 glutathione = tert-butanol + glutathione disulfide + H2O (RHEA:69412)
• cumene hydroperoxide + 2 glutathione = 2-phenylpropan-2-ol + glutathione disulfide + H2O (RHEA:69651)
• (9S)-hydroperoxy-(10E,12Z)-octadecadienoate + 2 glutathione = (9S)-hydroxy-(10E,12Z)-octadecadienoate + glutathione disulfide + H2O (RHEA:76687)
• (12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 glutathione = (12R)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + glutathione disulfide + H2O (RHEA:76691)
• (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + 2 glutathione = (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + glutathione disulfide + H2O (RHEA:76695)
• (5S)-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + glutathione disulfide + H2O (RHEA:76699)
• (12S)-hydroperoxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate + 2 glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate + glutathione disulfide + H2O (RHEA:76703)

UniProt features (39 total): helix 10, modified residue 9, strand 7, sequence variant 5, splice variant 2, chain 1, active site 1, site 1, sequence conflict 1, turn 1, non-standard amino acid 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2F8A	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

No AlphaFold model available for P07203 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (2): 49; 49 (subject to oxidation and hydroselenide loss to dehydroalanine)

Post-translational modifications (9): 148, 197, 201, 34, 88, 88, 114, 114, 148

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2142688	Synthesis of 5-eicosatetraenoic acids
R-HSA-2142712	Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-2142770	Synthesis of 15-eicosatetraenoic acid derivatives
R-HSA-3299685	Detoxification of Reactive Oxygen Species

MSigDB gene sets: 508 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, MODULE_93, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_REGULATION_OF_MAMMARY_GLAND_EPITHELIAL_CELL_PROLIFERATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_EPITHELIAL_CELL_DEVELOPMENT

GO Biological Process (55): temperature homeostasis (GO:0001659), endothelial cell development (GO:0001885), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), triglyceride metabolic process (GO:0006641), glutathione metabolic process (GO:0006749), sensory perception of sound (GO:0007605), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), response to xenobiotic stimulus (GO:0009410), response to symbiotic bacterium (GO:0009609), UV protection (GO:0009650), response to hormone (GO:0009725), response to selenium ion (GO:0010269), response to gamma radiation (GO:0010332), arachidonate metabolic process (GO:0019369), lipoxygenase pathway (GO:0019372), response to estradiol (GO:0032355), response to lipopolysaccharide (GO:0032496), response to hydroperoxide (GO:0033194), response to vitamin E (GO:0033197), regulation of mammary gland epithelial cell proliferation (GO:0033599), cellular response to oxidative stress (GO:0034599), response to nicotine (GO:0035094), epigenetic regulation of gene expression (GO:0040029), vasodilation (GO:0042311), response to hydrogen peroxide (GO:0042542), hydrogen peroxide catabolic process (GO:0042744), skeletal muscle tissue regeneration (GO:0043403), blood vessel endothelial cell migration (GO:0043534), fat cell differentiation (GO:0045444), myoblast differentiation (GO:0045445), cell redox homeostasis (GO:0045454), fibroblast proliferation (GO:0048144), skeletal muscle fiber development (GO:0048741), neuron apoptotic process (GO:0051402), myoblast proliferation (GO:0051450), response to folic acid (GO:0051593), biological process involved in interaction with symbiont (GO:0051702), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), heart contraction (GO:0060047), angiogenesis involved in wound healing (GO:0060055)

GO Molecular Function (7): glutathione peroxidase activity (GO:0004602), SH3 domain binding (GO:0017124), phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066), protein tyrosine kinase binding (GO:1990782), peroxidase activity (GO:0004601), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), Lewy body (GO:0097413)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Arachidonate metabolism	3
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxygen-containing compound	4
response to chemical	3
icosanoid metabolic process	2
response to lipid	2
peroxidase activity	2
cellular anatomical structure	2
cytoplasm	2
multicellular organismal-level homeostasis	1
epithelial cell development	1
endothelial cell differentiation	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
acylglycerol metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
sensory perception of mechanical stimulus	1
intrinsic apoptotic signaling pathway	1
response to symbiont	1
response to bacterium	1
response to UV	1
response to endogenous stimulus	1
response to ionizing radiation	1
long-chain fatty acid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
fatty acid metabolic process	1
response to molecule of bacterial origin	1
response to oxidative stress	1
response to vitamin	1
mammary gland epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
protein domain specific binding	1
protein kinase binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
binding	1
catalytic activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

61 interactions, top by confidence:

A	B	Type	Score
AAGAB	AP2A2	psi-mi:“MI:0914”(association)	0.670
rep	GPX1	psi-mi:“MI:0914”(association)	0.660
GPX1	rep	psi-mi:“MI:0915”(physical association)	0.660
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
IGFBP4	CETN3	psi-mi:“MI:0914”(association)	0.530
CFTR	GPX1	psi-mi:“MI:0915”(physical association)	0.520
	GPX1	psi-mi:“MI:0407”(direct interaction)	0.440
	GPX1	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
GPX1	FGL2	psi-mi:“MI:0915”(physical association)	0.400
VAX2	GPX1	psi-mi:“MI:0915”(physical association)	0.400
GPX1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
ARHGAP11B	RPN1	psi-mi:“MI:0914”(association)	0.350
G	GPX1	psi-mi:“MI:0914”(association)	0.350
rep	GPX1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
TMIGD1	DDX39A	psi-mi:“MI:0914”(association)	0.350
DNAJB3	MEIS1	psi-mi:“MI:0914”(association)	0.350
MRM1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
RNF4	KPNA3	psi-mi:“MI:0914”(association)	0.350
MINDY2	SLC27A2	psi-mi:“MI:0914”(association)	0.350
TICAM1	INPPL1	psi-mi:“MI:0914”(association)	0.350
HOXB6	AHCYL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Proximity Label-MS), GPX1 (Affinity Capture-MS), GPX1 (Affinity Capture-MS), NAGK (Negative Genetic), GPX1 (Negative Genetic), OXT (Negative Genetic), SRC (Negative Genetic), GPX1 (Negative Genetic), TSPO (Negative Genetic)

ESM2 similar proteins: A6QLU8, O18994, O46607, O70325, O75715, P00435, P04041, P07203, P11352, P11909, P18283, P21765, P22352, P23764, P28714, P36968, P36969, P36970, P37141, P46412, P83645, P97346, Q0EF98, Q0EF99, Q0EFA0, Q32QL6, Q4AEG9, Q4AEH0, Q4AEH1, Q4AEH2, Q4AEH3, Q4AEH4, Q4AEH5, Q4AEH7, Q4AEH8, Q4AEH9, Q4AEI0, Q4AEI1, Q4AEI2, Q4AEI3

Diamond homologs: A1KV41, A6QLY2, G9JJU2, O02621, O04922, O08368, O18994, O22448, O22850, O23814, O23968, O23970, O24031, O24296, O32770, O46607, O48646, O49069, O59858, O62327, O70325, O75715, P00435, P04041, P06610, P07203, P0A0T4, P0A0T5, P0C2T0, P11352, P11909, P18283, P21765, P22352, P28714, P30708, P30710, P35666, P36014, P36968

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	GPX1	phosphorylation
ABL2	“up-regulates activity”	GPX1	phosphorylation
PPARGC1A	up-regulates	GPX1

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	0
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

205 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49357747:CCTAC:C	acceptor_loss	0.9900
3:49357748:C:CC	acceptor_gain	0.9900
3:49357748:C:T	acceptor_loss	0.9900
3:49357749:T:A	acceptor_loss	0.9900
3:49358021:GCGCA:G	donor_loss	0.9900
3:49358022:CGCA:C	donor_loss	0.9900
3:49358023:GCAC:G	donor_loss	0.9900
3:49358024:CACC:C	donor_loss	0.9900
3:49358025:A:C	donor_loss	0.9900
3:49358026:C:G	donor_loss	0.9900
3:49358062:C:CT	donor_gain	0.9900
3:49358063:C:CT	donor_gain	0.9900
3:49357745:CTC:C	acceptor_gain	0.9800
3:49357743:TTCTC:T	acceptor_gain	0.9700
3:49357746:TC:T	acceptor_gain	0.9700
3:49357747:CC:C	acceptor_gain	0.9700
3:49358038:A:AC	donor_gain	0.9500
3:49358039:C:CC	donor_gain	0.9500
3:49358449:T:TA	donor_gain	0.9200
3:49357751:C:CT	acceptor_gain	0.9100
3:49357929:T:A	donor_gain	0.9000
3:49358025:A:AC	donor_gain	0.8900
3:49358026:C:CC	donor_gain	0.8900
3:49358454:AG:A	donor_gain	0.8600
3:49357752:A:T	acceptor_gain	0.8400
3:49357744:TCTC:T	acceptor_gain	0.8100
3:49357745:CTCC:C	acceptor_gain	0.8100
3:49357746:TCCT:T	acceptor_gain	0.8100
3:49358455:G:C	donor_gain	0.7900
3:49358500:T:TA	donor_gain	0.7900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000444187 (3:49358421 C>A,T), RS1000612014 (3:49358259 G>A,T), RS1000738694 (3:49358627 A>G), RS1002388962 (3:49358119 G>A,T), RS1003362206 (3:49357290 TC>T), RS1004018221 (3:49358405 T>C), RS1004153945 (3:49358543 G>C,T), RS1004253459 (3:49358733 G>A,C), RS1006363504 (3:49359672 C>G), RS1006517702 (3:49360022 G>C), RS1006683422 (3:49357826 CTA>C), RS1007956020 (3:49358338 G>C), RS1009335994 (3:49358404 G>A,T), RS1010298035 (3:49359588 T>C), RS1013390476 (3:49359528 ACTTT>A)

Disease associations

OMIM: gene MIM:138320 | disease phenotypes: MIM:614164

GenCC curated gene-disease

Disease	Classification	Inheritance
gluthathione peroxidase deficiency	Limited	Autosomal recessive

Mondo (1): gluthathione peroxidase deficiency (MONDO:0013601)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003265	Neonatal hyperbilirubinemia
HP:0004863	Compensated hemolytic anemia
HP:0020082	Heinz bodies

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000879_45	Crohn’s disease	6.000000e-17
GCST001725_77	Inflammatory bowel disease	1.000000e-47
GCST002548_9	Ulcerative colitis	8.000000e-07
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005316_110	Intelligence (MTAG)	5.000000e-24
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST008357_20	Mood instability	4.000000e-11
GCST009524_221	Household income (MTAG)	5.000000e-22
GCST010083_170	Hemoglobin levels	6.000000e-11
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008475	mood instability measurement
EFO:0009695	household income
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2163186 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1050450	GPX1		0.00	0

Binding affinities (BindingDB)

2 measured of 4 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
640/359	KI	32700 nM
CEFOPERAZONE	KI	245000 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 21 total; 1 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-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178708: Inhibition of GPX1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Hydrogen Peroxide	affects abundance, decreases activity, increases expression, decreases expression, affects cotreatment (+4 more)	10
Selenium	affects response to substance, affects activity, decreases expression, increases activity, increases expression	10
Sodium Selenite	decreases reaction, increases activity, increases expression	9
Particulate Matter	increases abundance, increases expression, decreases expression	8
Doxorubicin	affects reaction, increases activity, increases expression, decreases reaction, increases abundance	7
Tobacco Smoke Pollution	decreases methylation, increases expression, increases reaction, affects expression, decreases expression	6
methylmercuric chloride	increases expression, decreases response to substance, decreases expression	5
bisphenol A	affects cotreatment, increases expression, decreases activity, decreases expression	5
sodium arsenite	decreases expression, decreases reaction, increases reaction, affects response to substance, affects cotreatment (+2 more)	5
Ascorbic Acid	affects cotreatment, increases expression, decreases expression, decreases reaction, increases abundance	5
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	5
ochratoxin A	affects activity, affects cotreatment, decreases expression, increases acetylation, increases expression (+1 more)	4
Resveratrol	increases activity, increases expression	4
Cisplatin	increases acetylation, decreases reaction, increases reaction, affects expression, affects cotreatment (+2 more)	4
Lipopolysaccharides	affects cotreatment, decreases expression, increases expression, increases reaction	4
Paraquat	decreases expression, increases expression, affects cotreatment, decreases reaction	4
Selenomethionine	affects expression, increases activity, increases expression, affects response to substance	4
Tretinoin	decreases expression, increases expression	4
cumene hydroperoxide	decreases response to substance, increases reduction	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Arsenic	affects expression, affects cotreatment, increases expression, decreases expression, increases abundance	3
Vehicle Emissions	decreases expression, increases abundance, increases expression	3
Quercetin	affects cotreatment, increases expression, decreases reaction	3
Vitamin E	affects cotreatment, increases expression, decreases activity, decreases reaction	3
1-Methyl-4-phenylpyridinium	decreases expression, decreases reaction, increases activity, increases reaction	3
Aflatoxin B1	increases expression, increases methylation	3
Palmitic Acid	affects cotreatment, affects expression, decreases expression, increases activity, increases expression (+1 more)	3
selenomethylselenocysteine	increases activity, increases expression	2
arsenite	affects binding, decreases reaction, increases reaction, increases expression	2
epigallocatechin gallate	affects cotreatment, increases expression, decreases expression	2

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2166444	Binding	Inhibition of glutathione peroxidase 1 in human bortezomib-resistant DOGUM cells assessed as decrease in bortezomib resistance ratio at 25 uM after 72 hrs by MTT assay	Identification of a glutathione peroxidase inhibitor that reverses resistance to anticancer drugs in human B-cell lymphoma cell lines. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2Y6	Abcam HEK293T GPX1 KO	Transformed cell line	Female
CVCL_SQ50	HAP1 GPX1 (-) 1	Cancer cell line	Male
CVCL_SQ51	HAP1 GPX1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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