Details for: GPX8

Gene ID: 493869

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GPX8

Ensembl ID: ENSG00000164294

Description: glutathione peroxidase 8 (putative)

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • extravillous trophoblast CL0008036
    CSI 8.23
    rCSI 10.18%
    PRS 93.88
  • bronchus fibroblast of lung CL2000093
    CSI 4.01
    rCSI 3.26%
    PRS 95.04
  • skin fibroblast CL0002620
    CSI 3.86
    rCSI 3.33%
    PRS 94.84
  • pancreatic stellate cell CL0002410
    CSI 3.62
    rCSI 21.08%
    PRS 95.93
  • blood vessel endothelial cell CL0000071
    CSI 3.44
    rCSI 7.14%
    PRS 94.27
  • neural crest cell CL0011012
    CSI 3.33
    rCSI 2.63%
    PRS 91.21
  • myofibroblast cell CL0000186
    CSI 3.24
    rCSI 4.48%
    PRS 93.26
  • stem cell CL0000034
    CSI 3.22
    rCSI 3.1%
    PRS 93.06
  • interstitial cell of Cajal CL0002088
    CSI 3.13
    rCSI 3.98%
    PRS 97.2
  • mesodermal cell CL0000222
    CSI 2.98
    rCSI 3.58%
    PRS 94.88
  • mucus secreting cell CL0000319
    CSI 2.87
    rCSI 4.56%
    PRS 97.44
  • multi-ciliated epithelial cell CL0005012
    CSI 2.76
    rCSI 2.75%
    PRS 91.12
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.67
    rCSI 2.57%
    PRS 94.18
  • mesenchymal stem cell CL0000134
    CSI 2.65
    rCSI 29.04%
    PRS 96.52
  • ciliated epithelial cell CL0000067
    CSI 2.5
    rCSI 2.2%
    PRS 89.04
  • chondrocyte CL0000138
    CSI 2.49
    rCSI 3.96%
    PRS 92.17
  • placental villous trophoblast CL2000060
    CSI 2.47
    rCSI 3.82%
    PRS 93.85
  • lung ciliated cell CL1000271
    CSI 2.42
    rCSI 2.8%
    PRS 91.4
  • radial glial cell CL0000681
    CSI 2.39
    rCSI 3.31%
    PRS 94.02
  • smooth muscle cell CL0000192
    CSI 2.13
    rCSI 5.08%
    PRS 91.59
  • glioblast CL0000030
    CSI 2.1
    rCSI 3.35%
    PRS 89.84
  • enteric smooth muscle cell CL0002504
    CSI 2.09
    rCSI 2.98%
    PRS 95.25
  • podocyte CL0000653
    CSI 1.88
    rCSI 8.36%
    PRS 95.12
  • alveolar adventitial fibroblast CL4028006
    CSI 1.86
    rCSI 2.93%
    PRS 96.06
  • vascular associated smooth muscle cell CL0000359
    CSI 1.71
    rCSI 5.55%
    PRS 94.21
  • stromal cell CL0000499
    CSI 1.67
    rCSI 4.69%
    PRS 92.72
  • tracheal goblet cell CL1000329
    CSI 1.66
    rCSI 3.62%
    PRS 95.75
  • keratocyte CL0002363
    CSI 1.52
    rCSI 3.65%
    PRS 95.55
  • mesenchymal cell CL0008019
    CSI 1.44
    rCSI 3.65%
    PRS 92.5
  • bronchial goblet cell CL1000312
    CSI 1.07
    rCSI 4.27%
    PRS 96.74
  • stromal cell of ovary CL0002132
    CSI 1.02
    rCSI 2.81%
    PRS 96.74
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.79
    rCSI 2.29%
    PRS 94.65
  • respiratory goblet cell CL0002370
    CSI 0.49
    rCSI 5.32%
    PRS 96.59
  • osteoblast CL0000062
    CSI 0.36
    rCSI 8.94%
    PRS 97.96

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GPX8](/details-gene/493869) is a putative glutathione peroxidase located on chromosome 5q11.2. As a member of the glutathione peroxidase family, its primary function is associated with cellular detoxification and the response to oxidative stress, specifically through its [peroxidase activity](/details-go/GO:0004601) within the [endoplasmic reticulum lumen](/details-go/GO:0005788). Expression data indicates that [GPX8](/details-gene/493869) is highly significant in a range of cell types involved in structural, secretory, and barrier functions. It is most prominent in [extravillous trophoblast](/details-cell/CL0008036) cells of the placenta, as well as in various fibroblast populations, including [bronchus fibroblast of lung](/details-cell/CL2000093) and [skin fibroblast](/details-cell/CL0002620), suggesting a key role in maintaining cellular homeostasis in metabolically active and environmentally exposed tissues. This gene was initially characterized as part of large-scale cDNA and genome sequencing projects ([Link](https://doi.org/10.1101/gr.2596504)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [GPX8](/details-gene/493869) points towards a specialized role in managing cellular stress in non-hematopoietic cell lineages. Its significance is highest in cell types characterized by high secretory activity, structural maintenance, or interaction with external environments. The most striking feature of its expression is its top-ranking significance in [extravillous trophoblast](/details-cell/CL0008036) cells (CSI: 8.23), which are critical for placental implantation and uterine remodeling. This suggests a vital function in protecting these invasive cells from the high oxidative stress inherent in their environment. Beyond the placenta, [GPX8](/details-gene/493869) demonstrates high significance across a spectrum of mesenchymal and epithelial cells. A prominent theme is its expression in fibroblasts and related cell types, including [bronchus fibroblast of lung](/details-cell/CL2000093), [skin fibroblast](/details-cell/CL0002620), [pancreatic stellate cell](/details-cell/CL0002410), and [myofibroblast cell](/details-cell/CL0000186). This pattern is consistent with a role in tissue repair and maintenance. Furthermore, its expression in [blood vessel endothelial cell](/details-cell/CL0000071), [mucus secreting cell](/details-cell/CL0000319), and [ciliated epithelial cell](/details-cell/CL0000067) indicates its importance in maintaining the integrity of vascular and mucosal barriers. The gene's presence in progenitor populations like [stem cell](/details-cell/CL0000034) and [mesenchymal stem cell](/details-cell/CL0000134) may also suggest a function in cellular differentiation and stress resistance during development. ## Pathways and Molecular Function The functional annotations for [GPX8](/details-gene/493869) strongly support its role as an antioxidant enzyme. It is directly implicated in [glutathione peroxidase activity](/details-go/GO:0004602), a key molecular function for neutralizing reactive oxygen species (ROS). This activity contributes to the broader biological processes of [cellular oxidant detoxification](/details-go/GO:0098869) and the [cellular response to oxidative stress](/details-go/GO:0034599). Its localization to the [endoplasmic reticulum lumen](/details-go/GO:0005788) is a critical aspect of its function. The ER is a major site of ROS production, particularly during protein folding. The presence of [GPX8](/details-gene/493869) in this compartment suggests it plays a specialized role in mitigating ER stress, ensuring proper protein synthesis and quality control. This is highly consistent with its expression in secretory cells like [fallopian tube secretory epithelial cell](/details-cell/CL4030006) and [mucus secreting cell](/details-cell/CL0000319), which have a high protein synthesis burden. Reactome pathway analysis places [GPX8](/details-gene/493869) within the context of generalized stress responses, including [Detoxification of reactive oxygen species](/details-reactome/R-HSA-3299685) and [Cellular response to chemical stress](/details-reactome/R-HSA-9711123), underscoring its broad importance in cellular defense mechanisms. ## Research Directions The specific expression pattern and established function of [GPX8](/details-gene/493869) as an ER-resident antioxidant enzyme provide a foundation for several testable hypotheses regarding its role in health and disease. 1. **Hypothesis 1: Role in Placentation and Pregnancy Disorders.** Given its exceptional significance in [extravillous trophoblast](/details-cell/CL0008036) cells, we hypothesize that [GPX8](/details-gene/493869) is essential for protecting the invading placenta from oxidative stress. Reduced [GPX8](/details-gene/493869) function or expression may lead to ER stress and apoptosis in trophoblasts, contributing to the pathogenesis of pre-eclampsia and other placental insufficiencies. 2. **Hypothesis 2: Involvement in Fibrotic Diseases.** The high significance of [GPX8](/details-gene/493869) in various fibroblast populations suggests it acts as a gatekeeper against stress-induced fibroblast-to-myofibroblast transition. It is hypothesized that downregulation of [GPX8](/details-gene/493869) in tissues like the lung or liver under chronic injury could exacerbate the fibrotic response by rendering fibroblasts more susceptible to pro-fibrotic stimuli. **Experimental Approach to Test Hypothesis 2:** To investigate the role of [GPX8](/details-gene/493869) in fibrosis, a key experiment would involve generating a conditional knockout of `Gpx8` in mouse fibroblasts. These mice, along with wild-type controls, could be subjected to a model of lung fibrosis, such as bleomycin administration. The degree of fibrosis would be quantified through histology (Masson's trichrome staining) and collagen deposition assays. Primary lung fibroblasts isolated from both genotypes could be cultured *in vitro* and treated with TGF-β to assess myofibroblast differentiation by measuring α-SMA expression and collagen secretion. RNA-sequencing of these cells would further elucidate the downstream pathways regulated by [GPX8](/details-gene/493869) in the context of fibrotic activation. **Therapeutic Potential:** As a protective enzyme, [GPX8](/details-gene/493869) is an unlikely target for inhibition. Instead, strategies aimed at **activating** or enhancing its function could be therapeutically beneficial in diseases characterized by high oxidative and ER stress, such as idiopathic pulmonary fibrosis or neurodegenerative disorders. However, its intracellular location within the endoplasmic reticulum makes it a difficult target for conventional small molecules or biologics. Therapeutic development would likely require novel approaches, such as gene therapy or the development of small molecule chaperones or activators capable of crossing multiple cellular membranes to reach the ER lumen.

Genular Protein ID: 1558946933

Symbol: GPX8_HUMAN

Name: Probable glutathione peroxidase 8

UniProtKB Accession Codes:

Q8TED1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EC 2 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIRSF 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 209
  • Mass: 23881
  • Checksum: 82DACC1A85FDF6D7
  • Sequence:
    • MEPLAAYPLK CSGPRAKVFA VLLSIVLCTV TLFLLQLKFL KPKINSFYAF EVKDAKGRTV 
SLEKYKGKVS LVVNVASDCQ LTDRNYLGLK ELHKEFGPSH FSVLAFPCNQ FGESEPRPSK 
EVESFARKNY GVTFPIFHKI KILGSEGEPA FRFLVDSSKK EPRWNFWKYL VNPEGQVVKF 
WKPEEPIEVI RPDIAALVRQ VIIKKKEDL

Genular Protein ID: 1969252971

Symbol: E7ETY7_HUMAN

Name: N/A

UniProtKB Accession Codes:

E7ETY7

Database IDs:

ARBA 9 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 4 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 IntAct 1 InterPro 4 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 1 PRINTS 1 PROSITE 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 Rhea 1 RuleBase 1 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 158
  • Mass: 18090
  • Checksum: C3F0656A122D8AEA
  • Sequence:
    • MEPLAAYPLK CSGPRAKVSL VVNVASDCQL TDRNYLGLKE LHKEFGPSHF SVLAFPCNQF 
GESEPRPSKE VESFARKNYG VTFPIFHKIK ILGSEGEPAF RFLVDSSKKE PRWNFWKYLV 
NPEGQVVKFW KPEEPIEVIR PDIAALVRQV IIKKKEDL

Genular Protein ID: 780733062

Symbol: J3KNB5_HUMAN

Name: N/A

UniProtKB Accession Codes:

J3KNB5

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 1 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 90
  • Mass: 10075
  • Checksum: 48838E2E07179BBB
  • Sequence:
    • MEPLAAYPLK CSGPRAKVFA VLLSIVLCTV TLFLLQLKFL KPKINSFYAF EVKDAKGRTV 
SLEKYKGKIL QRRNQGGIFG SILSTLRVKL

Genular Protein ID: 1646603876

Symbol: B4DPY0_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DPY0

Database IDs:

ARBA 9 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 4 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 3 Gene3D 1 InterPro 4 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 1 PRINTS 1 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 1 Rhea 1 RuleBase 1 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 158
  • Mass: 18118
  • Checksum: C3F0657283A48AEA
  • Sequence:
    • MEPLAAYPLK CSGPRAKVSL VVNVASDCQL TDRNYLGLKE LHKEFGPSHF SVLAFPCNQF 
GESEPRPSKE VESFARKNYG VTFPIFHKIK ILGSEGEPAF RFLVDSSKKE PRWNFWKYLV 
NPEGQVVKFW RPEEPIEVIR PDIAALVRQV IIKKKEDL