GPX2 | ENSG00000176153 | NCBI 2877

Details for: GPX2

Gene ID: 2877

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: GPX2

Ensembl ID: ENSG00000176153

Description: glutathione peroxidase 2

Cell Significance Landscape

Display Count:

Associated with

Arachidonate metabolism
(R-HSA-2142753)
Cellular responses to stimuli
(R-HSA-8953897)
Cellular responses to stress
(R-HSA-2262752)
Cellular response to chemical stress
(R-HSA-9711123)
Detoxification of reactive oxygen species
(R-HSA-3299685)
Fatty acid metabolism
(R-HSA-8978868)
Gene expression (transcription)
(R-HSA-74160)
Generic transcription pathway
(R-HSA-212436)
Metabolism
(R-HSA-1430728)
Metabolism of lipids
(R-HSA-556833)
Rna polymerase ii transcription
(R-HSA-73857)
Synthesis of 5-eicosatetraenoic acids
(R-HSA-2142688)
Synthesis of 12-eicosatetraenoic acid derivatives
(R-HSA-2142712)
Synthesis of 15-eicosatetraenoic acid derivatives
(R-HSA-2142770)
Tp53 regulates metabolic genes
(R-HSA-5628897)
Transcriptional regulation by tp53
(R-HSA-3700989)
Cellular oxidant detoxification
(GO:0098869)
Cytoplasm
(GO:0005737)
Cytosol
(GO:0005829)
Electron transfer activity
(GO:0009055)
Glutathione peroxidase activity
(GO:0004602)
Intercellular bridge
(GO:0045171)
Mitotic spindle
(GO:0072686)
Phospholipid-hydroperoxide glutathione peroxidase activity
(GO:0047066)
Response to oxidative stress
(GO:0006979)

Significant Cells

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

transit amplifying cell of colon CL0009011

CSI 38.04

rCSI 44.68%

PRS 98.83
stem cell CL0000034

CSI 34.14

rCSI 32.91%

PRS 98.06
foveolar cell of stomach CL0002179

CSI 24.94

rCSI 53.09%

PRS 98.65
mucous neck cell CL0000651

CSI 22.41

rCSI 32.29%

PRS 98.54
brush cell CL0002204

CSI 20.41

rCSI 40.41%

PRS 98.22
pancreatic D cell CL0000173

CSI 19.34

rCSI 19.02%

PRS 98.46
hepatocyte CL0000182

CSI 18.63

rCSI 33.34%

PRS 97.23
transit amplifying cell CL0009010

CSI 18.56

rCSI 28.39%

PRS 99.02
M cell of gut CL0000682

CSI 18.38

rCSI 19.53%

PRS 98.61
colon goblet cell CL0009039

CSI 18.37

rCSI 43.67%

PRS 98.63
ciliated cell CL0000064

CSI 18.01

rCSI 29.18%

PRS 95.71
paneth cell CL0000510

CSI 15.85

rCSI 23.4%

PRS 99.24
colon epithelial cell CL0011108

CSI 15.77

rCSI 16.52%

PRS 98.02
nasal mucosa goblet cell CL0002480

CSI 15.61

rCSI 18.1%

PRS 97.84
midzonal region hepatocyte CL0019028

CSI 15.28

rCSI 35.86%

PRS 96.71
multi-ciliated epithelial cell CL0005012

CSI 14.81

rCSI 14.78%

PRS 96.37
goblet cell CL0000160

CSI 14.69

rCSI 13.88%

PRS 97.87
secretory cell CL0000151

CSI 13.26

rCSI 13.84%

PRS 98.14
intestine goblet cell CL0019031

CSI 11.98

rCSI 10.64%

PRS 97.81
intestinal crypt stem cell of small intestine CL0009017

CSI 11.55

rCSI 31.13%

PRS 98.81
corneal epithelial cell CL0000575

CSI 10.86

rCSI 31.06%

PRS 98.35
intestinal tuft cell CL0019032

CSI 10.4

rCSI 15.9%

PRS 98.2
intrahepatic cholangiocyte CL0002538

CSI 10.3

rCSI 24.72%

PRS 98.24
basal cell CL0000646

CSI 9.38

rCSI 12.54%

PRS 97.6
BEST4+ enteroycte CL4030026

CSI 8.97

rCSI 11.15%

PRS 97.88
paneth cell of epithelium of small intestine CL1000343

CSI 8.87

rCSI 24.85%

PRS 98.87
pulmonary ionocyte CL0017000

CSI 8.56

rCSI 10.42%

PRS 98.89
conjunctival epithelial cell CL1000432

CSI 8.2

rCSI 12.53%

PRS 97.79
lung neuroendocrine cell CL1000223

CSI 8.18

rCSI 12.09%

PRS 98
Kupffer cell CL0000091

CSI 8.09

rCSI 18.49%

PRS 98.65
intestinal crypt stem cell of colon CL0009043

CSI 7.72

rCSI 58%

PRS 99.28
tracheal goblet cell CL1000329

CSI 7.57

rCSI 16.52%

PRS 98.74
pancreatic ductal cell CL0002079

CSI 7.26

rCSI 14.12%

PRS 98.43
type L enteroendocrine cell CL0002279

CSI 7.1

rCSI 13.32%

PRS 98.33
enteroendocrine cell CL0000164

CSI 7.03

rCSI 9.61%

PRS 97.38
squamous epithelial cell CL0000076

CSI 6.63

rCSI 15.74%

PRS 95.87
pancreatic acinar cell CL0002064

CSI 6.51

rCSI 8.66%

PRS 98.56
dendritic cell CL0000451

CSI 6.5

rCSI 8.01%

PRS 97.63
epithelial cell CL0000066

CSI 6.45

rCSI 9.91%

PRS 93.46
periportal region hepatocyte CL0019026

CSI 6.32

rCSI 24.57%

PRS 96.57
hepatic stellate cell CL0000632

CSI 6.14

rCSI 23%

PRS 97.71
ciliated epithelial cell CL0000067

CSI 6.11

rCSI 5.38%

PRS 95.4
respiratory basal cell CL0002633

CSI 6.08

rCSI 6.3%

PRS 98.74
respiratory hillock cell CL4030023

CSI 6.06

rCSI 10.81%

PRS 99.09
enterocyte CL0000584

CSI 5.9

rCSI 9.51%

PRS 97.03
ionocyte CL0005006

CSI 5.86

rCSI 6.28%

PRS 98.75
transit amplifying cell of small intestine CL0009012

CSI 5.6

rCSI 24.58%

PRS 98.95
intestinal epithelial cell CL0002563

CSI 5.2

rCSI 5.43%

PRS 97.74
enteroendocrine cell of small intestine CL0009006

CSI 5.01

rCSI 11.02%

PRS 98.39
centrilobular region hepatocyte CL0019029

CSI 4.94

rCSI 12.89%

PRS 96.25
glial cell CL0000125

CSI 4.82

rCSI 18.35%

PRS 95.97
type B pancreatic cell CL0000169

CSI 4.5

rCSI 9.97%

PRS 98.11
enterocyte of epithelium of large intestine CL0002071

CSI 4.28

rCSI 22.49%

PRS 98.73
club cell CL0000158

CSI 4.01

rCSI 5.88%

PRS 97.88
ciliated columnar cell of tracheobronchial tree CL0002145

CSI 3.7

rCSI 8.43%

PRS 95.31
IgA plasma cell CL0000987

CSI 3.31

rCSI 3.38%

PRS 96.77
respiratory suprabasal cell CL4033048

CSI 3.25

rCSI 4.17%

PRS 98.87
pancreatic PP cell CL0002275

CSI 3.18

rCSI 12.67%

PRS 98.1
duct epithelial cell CL0000068

CSI 3.1

rCSI 4.53%

PRS 99.33
paneth cell of colon CL0009009

CSI 3.09

rCSI 30.39%

PRS 98.76
colonocyte CL1000347

CSI 2.97

rCSI 4.26%

PRS 97.97
neuroendocrine cell CL0000165

CSI 2.52

rCSI 9.75%

PRS 98.31
basal cell of epithelium of trachea CL1000348

CSI 2.07

rCSI 14.64%

PRS 98.24
enterocyte of epithelium of small intestine CL1000334

CSI 1.79

rCSI 27.68%

PRS 98.33
small intestine goblet cell CL1000495

CSI 1.74

rCSI 3.8%

PRS 98.61
epithelial cell of urethra CL1000296

CSI 1.47

rCSI 37.03%

PRS 98.67
pancreatic epsilon cell CL0005019

CSI 1.44

rCSI 6.69%

PRS 98.23
parietal cell CL0000162

CSI 1.31

rCSI 11.26%

PRS 97.88
enteroendocrine cell of colon CL0009042

CSI 1.31

rCSI 6.13%

PRS 98.16
epithelial cell of esophagus CL0002252

CSI 1.07

rCSI 10.6%

PRS 96.23

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.

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.

Context Genes (max 20):

Interaction Source:

Pathway Categories (for ONTOLOGY source):

Baseline Cell Type:

Baseline Cell Context(s): Comma-separated if multiple.

Target Cell Type:

Target Cell Context(s): Comma-separated if multiple.

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.

Description
Proteins

## Summary [GPX2](/details-gene/2877) (Glutathione Peroxidase 2) is a protein-coding gene located on chromosome 14q23.3. It encodes a key selenium-dependent enzyme that plays a critical role in the cellular defense against oxidative damage. Functionally, [GPX2](/details-gene/2877) is involved in the detoxification of reactive oxygen species (ROS), particularly hydroperoxides, by catalyzing the reduction of these molecules using glutathione. Its expression is highly enriched in the epithelial linings of the gastrointestinal tract, as demonstrated by its significant expression in cells such as the `[transit amplifying cell of colon](/details-cell/CL0009011)` and `[foveolar cell of stomach](/details-cell/CL0002179)`. This specific localization suggests a specialized function in protecting tissues that are constantly exposed to oxidative and chemical stress from diet, microbes, and metabolic activity. ## Cellular Roles and Expression Landscape The expression profile of [GPX2](/details-gene/2877) points to a highly specialized role as a guardian of epithelial integrity, particularly within the digestive system. **Overall**, the gene shows its highest significance in rapidly dividing and functionally active epithelial cells of the gut. It is a top marker for `[transit amplifying cell of colon](/details-cell/CL0009011)` (CSI: 38.04) and `[stem cell](/details-cell/CL0000034)` (CSI: 34.14), suggesting a crucial role in protecting the proliferative compartments of the intestinal crypt from oxidative DNA damage. This protective function extends throughout the gastrointestinal tract, with high significance in secretory cells such as `[foveolar cell of stomach](/details-cell/CL0002179)` (CSI: 24.94), `[mucous neck cell](/details-cell/CL0000651)` (CSI: 22.41), and `[colon goblet cell](/details-cell/CL0009039)` (CSI: 18.37). Its presence in specialized absorptive cells like the `[M cell of gut](/details-cell/CL0000682)` and defensive cells like the `[paneth cell](/details-cell/CL0000510)` further underscores its importance in maintaining mucosal homeostasis. Beyond the gut, its notable expression in `[hepatocyte](/details-cell/CL0000182)`s (CSI: 18.63) is consistent with a broader role in systemic detoxification processes centered in the liver. The expression pattern strongly indicates that [GPX2](/details-gene/2877) is a fundamental component of the antioxidant defense system in tissues that form a primary barrier to the external environment. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [GPX2](/details-gene/2877) are centered on redox homeostasis and cellular stress response. As its name implies, its primary molecular function is `[glutathione peroxidase activity](/details-go/GO:0004602)`, enabling it to participate directly in the `[cellular oxidant detoxification](/details-go/GO:0098869)` process. This activity is vital for the broader biological `[response to oxidative stress](/details-go/GO:0006979)`. Analysis of Reactome pathways reinforces this role, placing [GPX2](/details-gene/2877) within the `[Detoxification of reactive oxygen species](/details-go/R-HSA-3299685)` and `[Cellular response to chemical stress](/details-go/R-HSA-9711123)` pathways. This is highly consistent with its expression in gastrointestinal and hepatic cells, which are frontline tissues for metabolizing xenobiotics and endogenous metabolic byproducts. Furthermore, its involvement in pathways such as `[Arachidonate metabolism](/details-go/R-HSA-2142753)` and `[Metabolism of lipids](/details-go/R-HSA-556833)` suggests a role in mitigating lipid peroxidation, a major source of cellular damage. Notably, [GPX2](/details-gene/2877) is linked to `[Transcriptional regulation by tp53](/details-go/R-HSA-3700989)`, indicating that its expression may be upregulated by the TP53 tumor suppressor protein as part of a coordinated response to cellular stress and DNA damage. ## Research Directions The highly specific expression of [GPX2](/details-gene/2877) in the gastrointestinal epithelium, particularly in stem and transit-amplifying cells, raises important questions about its role in tissue homeostasis, inflammatory diseases, and cancer. **Proposed Hypotheses:** 1. **[GPX2](/details-gene/2877) is essential for preserving the integrity of the intestinal stem cell (ISC) niche.** Given its high significance in ISCs and their proliferative progeny, it is hypothesized that [GPX2](/details-gene/2877) acts as a critical defender against ROS generated during high metabolic activity and exposure to luminal contents. Its loss would lead to increased DNA damage in ISCs, impairing epithelial regeneration and increasing susceptibility to colitis and colitis-associated colorectal cancer. 2. **Upregulation of [GPX2](/details-gene/2877) is a key survival mechanism for colorectal cancer (CRC) cells.** While protective in healthy tissue, the potent antioxidant function of [GPX2](/details-gene/2877) may be co-opted by cancer cells to withstand the high levels of oxidative stress inherent to tumorigenesis and to resist ROS-inducing chemo- and radiotherapies. **Key Experimental Approach:** To test the first hypothesis regarding the role of [GPX2](/details-gene/2877) in the intestinal stem cell niche, a conditional knockout mouse model could be employed. Specifically, mice with a floxed `Gpx2` allele could be crossed with `Lgr5-EGFP-IRES-CreERT2` mice to enable tamoxifen-inducible deletion of `Gpx2` specifically in intestinal stem cells. Following deletion, these mice and their wild-type littermates could be challenged with dextran sodium sulfate (DSS) to induce colitis. The role of [GPX2](/details-gene/2877) would be assessed by comparing disease severity (weight loss, colon length), histological damage, apoptosis (cleaved caspase-3 staining), DNA damage (γH2AX staining) in crypts, and regenerative capacity via ex vivo organoid formation assays. **Therapeutic Potential:** The therapeutic potential of targeting [GPX2](/details-gene/2877) is context-dependent. As a protective enzyme, strategies to enhance its activity or expression could be beneficial in inflammatory conditions like inflammatory bowel disease (IBD), where excessive oxidative stress contributes to tissue damage. Conversely, in the context of colorectal cancer, where [GPX2](/details-gene/2877) is often overexpressed, it represents a potential target for **inhibition**. Developing small molecule inhibitors for this intracellular enzyme could sensitize cancer cells to oxidative stress, thereby enhancing the efficacy of conventional therapies such as radiation and certain chemotherapeutics. This dual role makes [GPX2](/details-gene/2877) a nuanced but potentially valuable therapeutic target.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

Glutathione peroxidase 2

Genular Protein ID: 2142087548

Symbol: GPX2_HUMAN

Name: Glutathione peroxidase 2

UniProtKB Accession Codes:

P18283 Q6PJ52 Q8WWI7 Q9NRP9

Database IDs:

Citations:

PubMed ID: 2388849

Title: A human cDNA sequence of a novel glutathione peroxidase-related protein.

PubMed ID: 2388849

DOI: 10.1093/nar/18.15.4619

PubMed ID: 8428933

Title: Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI.

PubMed ID: 8428933

DOI: 10.1016/s0021-9258(18)53812-6

PubMed ID: 10806356

Title: Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional response to exogenous redox agents.

PubMed ID: 10806356

DOI: 10.1016/s0378-1119(00)00137-2

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 36608588

Title: Side-by-side comparison of recombinant human glutathione peroxidases identifies overlapping substrate specificities for soluble hydroperoxides.

PubMed ID: 36608588

DOI: 10.1016/j.redox.2022.102593

Sequence Information:

Length: 190
Mass: 21954
Checksum: FC8C4E69C4DE83A0
Sequence:

MAFIAKSFYD LSAISLDGEK VDFNTFRGRA VLIENVASLU GTTTRDFTQL NELQCRFPRR 
LVVLGFPCNQ FGHQENCQNE EILNSLKYVR PGGGYQPTFT LVQKCEVNGQ NEHPVFAYLK 
DKLPYPYDDP FSLMTDPKLI IWSPVRRSDV AWNFEKFLIG PEGEPFRRYS RTFPTINIEP 
DIKRLLKVAI

Details for: GPX2

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

A human cDNA sequence of a novel glutathione peroxidase-related protein. PubMed ID: 2388849

Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. PubMed ID: 8428933

Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional response to exogenous redox agents. PubMed ID: 10806356

The DNA sequence and analysis of human chromosome 14. PubMed ID: 12508121

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Initial characterization of the human central proteome. PubMed ID: 21269460