GPX1 glutathione peroxidase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GPX1provided by HGNC
Official Full Name: glutathione peroxidase 1provided by HGNC
Primary source: HGNC:HGNC:4553
See related: Ensembl:ENSG00000233276 MIM:138320; AllianceGenome:HGNC:4553
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GPXD; GSHPX1
Summary: 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. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in fat (RPKM 212.4), spleen (RPKM 100.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (49357176..49358353, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (49386555..49387726, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (49394609..49395786, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.
Title: Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.
Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma.
Title: Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma.
Variation of the genes encoding antioxidant enzymes SOD2 (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male infertility: a genetic association study and in silico analysis.
Title: Variation of the genes encoding antioxidant enzymes SOD2 (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male infertility: a genetic association study and in silico analysis.
The mRNA expression of genes encoding selected antioxidant enzymes and thioredoxin, and the concentrations of their protein products in gingival crevicular fluid and saliva during periodontitis.
Title: The mRNA expression of genes encoding selected antioxidant enzymes and thioredoxin, and the concentrations of their protein products in gingival crevicular fluid and saliva during periodontitis.
Polyalanine polymorphism in the signal peptide of Glutathione peroxidase 1 (GPX1) gene & its association with osteoporosis.
Title: Polyalanine polymorphism in the signal peptide of Glutathione peroxidase 1 (GPX1) gene & its association with osteoporosis.
Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness.
Title: Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness.
Genetic polymorphism impact superoxide dismutase and glutathione peroxidase activity in charcoal workers.
Title: Genetic polymorphism impact superoxide dismutase and glutathione peroxidase activity in charcoal workers.
The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer.
Title: The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer.
Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma.
Title: Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma.
Salvianolic acid B inhibits myocardial I/R-induced ROS generation and cell apoptosis by regulating the TRIM8/GPX1 pathway.
Title: Salvianolic acid B inhibits myocardial I/R-induced ROS generation and cell apoptosis by regulating the TRIM8/GPX1 pathway.

Submit: New GeneRIF Correction See all GeneRIFs (280)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Gluthathione peroxidase deficiency MedGen: C0398747 OMIM: 614164 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1) protect neuronal cells from HIV-1 gp120-induced programmed cell death	PubMed
Tat	tat	Exposure to HIV-1 clade B Tat protein has a greater inhibition of GSS, GPx1, SOD1, and CAT expression compared with exposure to clade C Tat protein in monocyte-derived immature dendritic cells	PubMed
	tat	HIV-1 Tat increases catalase and glutathione peroxidase 1 (GPX1) activities in human cardiac myocyte	PubMed
	tat	Cotransduction with both SOD1 and GPx1 significantly prevents Tat-mediated increases in intracellular Ca2+ fluxes	PubMed
	tat	HIV-1 induced neuron apoptosis is protected by transduction with antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase (GPx1)	PubMed
	tat	HIV-1 Tat causes a greater than 50% decrease in intracellular reduced glutathione (GSH), leading to the extracellular appearance of acidic FGF-1, an effect that is partially mediated through modulation of GSH biosynthetic enzymes	PubMed
	tat	Expression of HIV-1 Tat in HeLa cells downregulates cytoplasmic glutathione peroxidase while upregulating phospholipid hydroperoxide glutathione peroxidase, thereby deregulating intracellular oxidant/antioxidant balance and amplifying UV sensitivity	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:181197 (e-PCR)
- UniSTS:155171

SHGC-76946 (e-PCR)
- UniSTS:34857

GDB:181211 (e-PCR)
- UniSTS:155179

D3S1330E (e-PCR)
- UniSTS:147343

A004T30 (e-PCR)
- UniSTS:72110

RH91501 (e-PCR)
- UniSTS:88496

WI-18922 (e-PCR)
- UniSTS:62388

RH45222 (e-PCR)
- UniSTS:8634

G34714 (e-PCR)
- UniSTS:11473

G60181 (e-PCR)
- UniSTS:137440

D21S1961 (e-PCR)
- UniSTS:37113

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables glutathione peroxidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutathione peroxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipid-hydroperoxide glutathione peroxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in UV protection	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in angiogenesis involved in wound healing	IEA Inferred from Electronic Annotation more info
involved_in arachidonate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in biological process involved in interaction with symbiont	IEA Inferred from Electronic Annotation more info
involved_in blood vessel endothelial cell migration	IEA Inferred from Electronic Annotation more info
involved_in cell redox homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular oxidant detoxification	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidative stress	NAS Non-traceable Author Statement more info	PubMed
involved_in endothelial cell development	IEA Inferred from Electronic Annotation more info
involved_in epigenetic regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in fat cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in glutathione metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutathione metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in heart contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hydrogen peroxide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in hydrogen peroxide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in lipoxygenase pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in myoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of release of cytochrome c from mitochondria	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of supramolecular fiber organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of proteasomal protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to folic acid	IEA Inferred from Electronic Annotation more info
involved_in response to gamma radiation	IEA Inferred from Electronic Annotation more info
involved_in response to hormone	IEA Inferred from Electronic Annotation more info
involved_in response to hydrogen peroxide	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hydrogen peroxide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to hydroperoxide	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in response to selenium ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to selenium ion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to symbiotic bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to vitamin E	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle fiber development	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle tissue regeneration	IEA Inferred from Electronic Annotation more info
involved_in temperature homeostasis	IEA Inferred from Electronic Annotation more info
involved_in triglyceride metabolic process	IEA Inferred from Electronic Annotation more info
involved_in vasodilation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
colocalizes_with Lewy body	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutathione peroxidase 1

Names: GSHPx-1; cellular glutathione peroxidase; phospholipid-hydroperoxide glutathione peroxidase GPX1; selenoprotein GPX1

NP_000572.2

EC 1.11.1.12

EC 1.11.1.9

NP_001316384.1

EC 1.11.1.12

EC 1.11.1.9

NP_001316431.1

EC 1.11.1.12

EC 1.11.1.9

NP_001316432.1

EC 1.11.1.12

EC 1.11.1.9

NP_958799.1

EC 1.11.1.12

EC 1.11.1.9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012264.1 RefSeqGene

Range

5006..6183

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000581.4 → NP_000572.2 glutathione peroxidase 1 isoform 1

See identical proteins and their annotated locations for NP_000572.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

BC007865, DA730294

Consensus CDS

CCDS43091.1

UniProtKB/Swiss-Prot

E9PAS1, P07203, Q7Z5H1, Q9BW12

UniProtKB/TrEMBL

A0A994J430, Q7L4Q3

Related

ENSP00000407375.1, ENST00000419783.3

Conserved Domains (1) summary

cd00340
Location:15 → 192

GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...
NM_001329455.2 → NP_001316384.1 glutathione peroxidase 1 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate, in-frame donor splice site at the 5' terminal exon, which results in the loss of the internal UGA stop codon compared to variant 1. The resulting isoform (5) is shorter, lacking an internal protein segment containing the selenocysteine residue, compared to isoform 1.

Source sequence(s)

DA583406, HM005391

Consensus CDS

CCDS87079.1

UniProtKB/TrEMBL

A0A2R8Y6B6, A0A994J4L4

Related

ENSP00000495108.1, ENST00000643797.2
NM_001329502.2 → NP_001316431.1 glutathione peroxidase 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate acceptor splice site at the 3' terminal exon, which causes a frameshift compared to variant 1. The resulting isoform (3) is shorter with a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC121247, BC007865, BP205653, DA730294

Consensus CDS

CCDS87078.1

UniProtKB/TrEMBL

A0A7I2YMD7

Related

ENSP00000493593.2, ENST00000496791.3
NM_001329503.2 → NP_001316432.1 glutathione peroxidase 1 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate acceptor splice site at the 3' terminal exon, which causes a frameshift compared to variant 1. The resulting isoform (4) is shorter with a distinct C-terminus compared to isoform 1.

Source sequence(s)

BC007865, BP213008, DA730294

Consensus CDS

CCDS87077.1

UniProtKB/TrEMBL

A0A7I2UQ36

Related

ENSP00000495001.2, ENST00000646881.3
NM_201397.3 → NP_958799.1 glutathione peroxidase 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) retains an intron, which causes a frameshift compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

BC007865, BI906726, DA730294

Consensus CDS

CCDS54582.1

UniProtKB/TrEMBL

A0A7I2YMD7

Related

ENSP00000391316.1, ENST00000419349.3

Conserved Domains (1) summary

cl00388
Location:16 → 84

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold