HPGD: Hydroxyprostaglandin Dehydrogenase 15-(NAD)
Key enzyme in prostaglandin degradation, associated with primary hypertrophic osteoarthropathy and colorectal cancer
Gene Information Card
| Symbol | HPGD |
|---|---|
| Full Name | 15-hydroxyprostaglandin dehydrogenase (NAD+) |
| Gene Type | Protein coding |
| Chromosomal Location | 4q34.1 |
| NCBI Gene ID | 3248 ncbi.nlm.nih.gov/gene/3248 |
| Ensembl ID | ENSG00000164120 |
| UniProt ID | P15428 |
| OMIM ID | 601688 |
| HGNC ID | 5154 |
| Aliases | 15-PGDH, PGDH1, SDR36C1 |
Description
The HPGD gene encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for the biological inactivation of prostaglandins, including PGE2. It catalyzes the oxidation of the 15(S)-hydroxyl group of prostaglandins, converting them into inactive 15-keto metabolites. This enzyme plays a critical role in regulating prostaglandin levels in tissues, influencing inflammation, pain, and cell proliferation. Loss-of-function mutations in HPGD cause primary hypertrophic osteoarthropathy (PHO), and reduced expression is associated with poor prognosis in colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary hypertrophic osteoarthropathy (PHO) | Loss-of-function mutations in HPGD lead to impaired prostaglandin degradation, resulting in elevated PGE2 levels that stimulate bone formation and digital clubbing. | OMIM #259100; ClinVar |
| Colorectal cancer | Reduced HPGD expression or promoter hypermethylation leads to increased PGE2 levels, promoting tumor growth and metastasis. | NCBI Gene; COSMIC |
| Gastric cancer | Downregulation of HPGD correlates with poor prognosis and increased PGE2 signaling. | UniProt; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 18.2 | Medium |
| Colon | 15.7 | Medium |
| Kidney | 12.4 | Medium |
| Liver | 8.9 | Low |
| Prostate | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 12.1 | Moderate expression |
| HCT116 (colorectal carcinoma) | 9.8 | Reduced compared to normal colon |
| HEK293 (embryonic kidney) | 7.5 | Basal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.175G>A (p.Gly59Arg) | Missense | Rare (PHO) | Loss of enzymatic activity |
| c.418C>T (p.Arg140*) | Nonsense | Rare (PHO) | Premature truncation, loss of function |
| c.563T>C (p.Leu188Pro) | Missense | Rare (PHO) | Impaired NAD+ binding |
Mutation functional classification
Loss of Function (LOF)
Most HPGD mutations in primary hypertrophic osteoarthropathy are loss-of-function, reducing or abolishing prostaglandin catabolism.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described.
View complete mutation data：
Gene Ontology (GO)
| • prostaglandin biosynthetic process (GO:0001516) | • cytoplasm (GO:0005737) |
| • oxidoreductase activity (GO:0016491) | • NAD binding (GO:0051287) |
| • prostaglandin metabolic process (GO:0006693) |
Pathways
• Prostaglandin synthesis and regulation (Reactome: R-HSA-2162123)
• Arachidonic acid metabolism (KEGG: hsa00590)
Protein Summary
15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a 266-amino acid cytosolic enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family. It uses NAD+ as a cofactor to oxidize the 15-hydroxyl group of prostaglandins, rendering them inactive. The enzyme is widely expressed in epithelial tissues, with highest activity in lung, colon, and kidney. Its crystal structure reveals a Rossmann fold for NAD+ binding and a catalytic triad (Ser138, Tyr151, Lys155) essential for activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HPGD Knockout HEK293 Cell Line | EDJ-KQ4932 | Human | 3248 | Details Get a Quote |
| HPGDS Knockout HEK293 Cell Line | EDJ-KQ8757 | Human | 27306 | Details Get a Quote |
| HPGD Knockout A-549 Cell Line | EDJ-KQ27772 | Human | 3248 | Details Get a Quote |
| HPGD Knockout HeLa Cell Line | EDJ-KQ27773 | Human | 3248 | Details Get a Quote |
| HPGDS Knockout HeLa Cell Line | EDJ-KQ56055 | Human | 27306 | Details Get a Quote |
| HPGDS Knockout A-549 Cell Line | EDJ-KQ64539 | Human | 27306 | Details Get a Quote |
| HPGD Knockout HCT 116 Cell Line | EDJ-KQ70514 | Human | 3248 | Details Get a Quote |
| HPGDS Knockout HCT 116 Cell Line | EDJ-KQ72998 | Human | 27306 | Details Get a Quote |
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