PTGS2 (COX-2): Gene, Function, and Clinical Significance
A comprehensive overview of the PTGS2 gene, encoding cyclooxygenase-2, its role in inflammation, cancer, and therapeutic targeting.
Gene Information Card
| Symbol | PTGS2 |
|---|---|
| Full Name | prostaglandin-endoperoxide synthase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 1q31.1 |
| NCBI Gene ID | 5743 ncbi.nlm.nih.gov/gene/5743 |
| Ensembl ID | ENSG00000073756 |
| UniProt ID | P35354 |
| OMIM ID | 600262 |
| HGNC ID | 9600 |
| Aliases | COX-2, COX2, PHS-2, PGHS-2, hCox-2 |
Description
The PTGS2 gene encodes prostaglandin-endoperoxide synthase 2, also known as cyclooxygenase-2 (COX-2). This enzyme is responsible for the conversion of arachidonic acid to prostaglandin H2, a precursor of various prostaglandins that mediate inflammation, pain, and fever. Unlike the constitutive COX-1, COX-2 is inducible by inflammatory stimuli, growth factors, and tumor promoters. PTGS2 is involved in various physiological processes including angiogenesis, immune response, and tissue homeostasis. Overexpression of PTGS2 is associated with chronic inflammation and multiple cancers, making it a key therapeutic target for nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Overexpression of COX-2 leads to increased prostaglandin E2 (PGE2) production, promoting cell proliferation, angiogenesis, and inhibiting apoptosis. | Multiple studies, including meta-analyses, show elevated COX-2 expression in colorectal tumors and association with poor prognosis. NSAIDs reduce risk. |
| Breast cancer | COX-2 overexpression in breast tumors correlates with aggressive phenotypes, hormone receptor negativity, and worse survival. PGE2 promotes tumor growth and metastasis. | Immunohistochemical studies and clinical trials of COX-2 inhibitors show potential benefit. |
| Alzheimer's disease | COX-2 is upregulated in the brain of Alzheimer's patients, contributing to neuroinflammation and amyloid plaque formation. | Epidemiological studies suggest NSAID use reduces risk of Alzheimer's disease. |
| Rheumatoid arthritis | COX-2 is induced by pro-inflammatory cytokines in synovial tissue, leading to joint inflammation and pain. | Selective COX-2 inhibitors are effective in reducing inflammation and pain in RA patients. |
| Gastric cancer | COX-2 overexpression is common in gastric cancer, associated with H. pylori infection and poor prognosis. | Studies show COX-2 inhibitors may suppress gastric cancer growth. |
| Lung cancer | COX-2 is overexpressed in non-small cell lung cancer (NSCLC), promoting tumor progression and resistance to chemotherapy. | Clinical trials of COX-2 inhibitors in combination with chemotherapy have shown mixed results. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.4 | Medium |
| Colon | 8.9 | Low |
| Breast | 5.2 | Low |
| Stomach | 7.1 | Low |
| Kidney | 3.4 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 15.3 | High expression, inducible by IL-1β |
| MCF7 (Breast carcinoma) | 6.8 | Moderate expression |
| HeLa (Cervical carcinoma) | 4.5 | Low expression |
| HCT116 (Colorectal carcinoma) | 12.1 | High expression |
| THP-1 (Monocyte) | 8.2 | Inducible by LPS |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.169C>T (p.Pro57Ser) | Missense | Rare (<0.1%) | Functional impact unknown; may affect enzyme activity |
| c.593G>A (p.Arg198His) | Missense | Rare | Potential loss of function; not well characterized |
| c.1129G>A (p.Val377Ile) | Missense | Rare | No known disease association |
| c.1462C>T (p.Arg488Trp) | Missense | Rare | Reported in cancer samples; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PTGS2 are extremely rare and not well documented. Complete loss of COX-2 activity is likely incompatible with normal physiology, as COX-2 is essential for various homeostatic functions. Some missense variants may reduce enzyme activity but are not clinically significant.
Gain of Function (GOF)
Gain-of-function mutations in PTGS2 are not commonly reported. Overexpression of the wild-type gene is more common in disease, driven by transcriptional upregulation rather than mutations. No activating mutations have been confirmed.
Dominant Negative (DN)
No dominant-negative mutations have been described for PTGS2. The enzyme functions as a homodimer, but mutations that disrupt dimerization or activity have not been characterized in human disease.
View complete mutation data：
Gene Ontology (GO)
| • cyclooxygenase activity | • prostaglandin-endoperoxide synthase activity |
| • heme binding | • peroxidase activity |
| • oxidoreductase activity | • lipid binding |
| • membrane | • endoplasmic reticulum |
| • nucleus | • cytoplasm |
| • inflammatory response | • prostaglandin biosynthetic process |
| • angiogenesis | • cell proliferation |
| • apoptotic process |
Pathways
• Arachidonic acid metabolism
• Prostaglandin synthesis
• COX-2 pathway
• Inflammatory response pathway
• NF-kappaB signaling
• MAPK signaling
• VEGF signaling
Protein Summary
The PTGS2 protein, also known as cyclooxygenase-2 (COX-2), is a membrane-bound enzyme of approximately 70 kDa. It catalyzes the rate-limiting step in the conversion of arachidonic acid to prostaglandin H2, which is then converted to various prostaglandins, prostacyclin, and thromboxane. COX-2 is inducible and plays a central role in inflammation, pain, and fever. It is also involved in tissue repair, renal function, and reproduction. The protein has two active sites: a cyclooxygenase site and a peroxidase site. It is the target of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs). Overexpression of COX-2 is linked to tumorigenesis, and its inhibition is a therapeutic strategy in cancer prevention and treatment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTGS2 Knockout HEK293 Cell Line | EDJ-KQ586 | Human | 5743 | Details Get a Quote |
| PTGS2 Knockout HeLa Cell Line | EDJ-KQ18034 | Human | 5743 | Details Get a Quote |
| PTGS2 Knockout A-549 Cell Line | EDJ-KQ19007 | Human | 5743 | Details Get a Quote |
| PTGS2 Knockout HCT 116 Cell Line | EDJ-KQ71222 | Human | 5743 | Details Get a Quote |
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