PTGS1 Gene (Prostaglandin-Endoperoxide Synthase 1): Function, Expression, and Clinical Significance
A comprehensive biomedical overview of PTGS1 (COX-1), including genomic data, tissue expression, disease associations, mutations, and pathway involvement.
Gene Information Card
| Symbol | PTGS1 |
|---|---|
| Full Name | Prostaglandin-Endoperoxide Synthase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q33.2 |
| NCBI Gene ID | 5742 ncbi.nlm.nih.gov/gene/5742 |
| Ensembl ID | ENSG00000095303 |
| UniProt ID | P23219 |
| OMIM ID | 176805 |
| HGNC ID | 9604 |
| Aliases | COX1, COX-1, PGH synthase 1, PHS1, PGHS-1, prostaglandin G/H synthase 1 |
Description
PTGS1 (prostaglandin-endoperoxide synthase 1) encodes cyclooxygenase-1 (COX-1), a key enzyme in prostaglandin biosynthesis. COX-1 converts arachidonic acid to prostaglandin H2 (PGH2), which is then converted to various prostanoids (e.g., prostacyclin, thromboxane A2). COX-1 is constitutively expressed in most tissues and plays a critical role in maintaining gastric mucosal integrity, platelet aggregation, and renal blood flow. It is the target of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin, which irreversibly inhibit its activity. PTGS1 is also implicated in inflammation, cancer, and cardiovascular diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric Ulcer | Inhibition of COX-1 reduces gastric mucosal prostaglandins, leading to decreased mucus and bicarbonate secretion and increased susceptibility to mucosal damage. | ClinVar: Pathogenic variants in PTGS1 are associated with increased risk of peptic ulcer disease; NSAID-induced ulcers are well-documented. |
| Thrombosis (Myocardial Infarction, Stroke) | COX-1 produces thromboxane A2 in platelets, promoting platelet aggregation. Loss of function or inhibition reduces thrombotic risk, but gain-of-function variants may increase risk. | ClinVar: Variants affecting COX-1 activity are linked to altered platelet function and thrombotic events. |
| Colorectal Cancer | COX-1 overexpression in colorectal tumors promotes prostaglandin E2 synthesis, which stimulates cell proliferation and inhibits apoptosis. | COSMIC: PTGS1 is overexpressed in colorectal cancer; somatic mutations are rare but may contribute to tumor progression. |
| Inflammatory Diseases (e.g., arthritis) | COX-1 contributes to basal prostaglandin production in inflamed tissues; inhibition by NSAIDs reduces inflammation but also causes GI side effects. | OMIM: PTGS1 is not directly mutated in arthritis, but its inhibition is a therapeutic target. |
| Familial Adenomatous Polyposis (FAP) | COX-1 inhibition may reduce polyp formation, but PTGS1 mutations are not primary; however, COX-1 expression is elevated in polyps. | COSMIC: PTGS1 expression changes are observed in FAP-associated colorectal tumors. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | High | Constitutive expression in gastric mucosa |
| Platelets | High | Constitutive expression in megakaryocytes/platelets |
| Kidney | Medium | Expression in renal medulla and cortex |
| Lung | Medium | Expression in bronchial epithelium |
| Liver | Low | Minimal expression |
| Brain | Low | Low expression in neurons |
| Heart | Low | Low expression in cardiac tissue |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Low | Low endogenous expression; often used for transfection studies |
| HeLa | Medium | Expression detected in cervical cancer cells |
| A549 | Medium | Lung carcinoma cell line with moderate COX-1 expression |
| MCF7 | Low | Breast cancer cell line with low COX-1 expression |
| HCT116 | High | Colorectal carcinoma cell line with high COX-1 expression |
| THP-1 | Medium | Monocytic leukemia cell line; expression increases upon differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.50C>T (p.Pro17Leu) | Missense | Rare (0.1% in general population) | May affect protein stability; clinical significance uncertain |
| c.230G>A (p.Arg77His) | Missense | Rare (0.05%) | Reported in patients with platelet dysfunction; reduced COX-1 activity |
| c.644C>T (p.Pro215Leu) | Missense | Rare (0.02%) | Associated with aspirin resistance in some studies |
| c.1123G>A (p.Val375Met) | Missense | Rare (0.01%) | Potential effect on enzyme activity; not well characterized |
| c.1621C>T (p.Arg541Trp) | Missense | Rare (0.03%) | Reported in gastric ulcer patients; may alter protein function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PTGS1 reduce or abolish COX-1 enzymatic activity, leading to decreased prostaglandin synthesis. This can impair platelet aggregation and gastric mucosal protection, potentially increasing bleeding risk and gastric ulcer susceptibility.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well documented. Some variants may increase enzyme activity, leading to enhanced thromboxane A2 production and increased thrombotic risk, but evidence is limited.
Dominant Negative (DN)
Dominant-negative effects have not been clearly established for PTGS1 mutations. Since COX-1 functions as a homodimer, some missense mutations might interfere with dimerization, but no confirmed dominant-negative variants are reported in ClinVar or literature.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004601 - peroxidase activity | • GO:0001516 - prostaglandin biosynthetic process |
| • GO:0006633 - fatty acid biosynthetic process | • GO:0005623 - cell |
| • GO:0005737 - cytoplasm | • GO:0005886 - plasma membrane |
| • GO:0016021 - integral component of membrane | • GO:0005515 - protein binding |
| • GO:0009055 - electron transfer activity | • GO:0019371 - cyclooxygenase pathway |
Pathways
• Arachidonic acid metabolism
• Prostaglandin synthesis and regulation
• COX-1 pathway (classic NSAID target)
• Thromboxane A2 receptor signaling
• Prostacyclin signaling via IP receptor
• Inflammatory response pathway
Protein Summary
PTGS1 encodes cyclooxygenase-1 (COX-1), a membrane-bound enzyme with both cyclooxygenase and peroxidase activities. It catalyzes the conversion of arachidonic acid to prostaglandin G2 (PGG2) and then to PGH2, the precursor of prostanoids. COX-1 is constitutively expressed in most tissues, particularly in the stomach, platelets, and kidneys, where it maintains homeostatic functions. The protein is a homodimer, each subunit containing a heme group. It is the primary target of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin, which irreversibly inhibit its activity, leading to anti-inflammatory, anti-pyretic, and anti-platelet effects. PTGS1 is also involved in cancer progression and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTGS1 Knockout HEK293 Cell Line | EDJ-KQ5584 | Human | 5742 | Details Get a Quote |
| PTGS1 Knockout HCT 116 Cell Line | EDJ-KQ28852 | Human | 5742 | Details Get a Quote |
| PTGS1 Knockout HeLa Cell Line | EDJ-KQ28853 | Human | 5742 | Details Get a Quote |
| PTGS1 Knockout A-549 Cell Line | EDJ-KQ62754 | Human | 5742 | Details Get a Quote |
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