HPGD

This gene encodes a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The encoded enzyme is responsible for the metabolism of prostaglandins, which function in a variety of physiologic and cellular processes such as inflammation. Mutations in this gene result in primary autosomal recessive hypertrophic osteoarthropathy and cranioosteoarthropathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

Full Name

hydroxyprostaglandin dehydrogenase 15-(NAD)

Function

Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites (PubMed:8086429, PubMed:10837478, PubMed:16828555, PubMed:16757471, PubMed:21916491, PubMed:25586183).

Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating proinflammatory cytokine expression (PubMed:25586183, PubMed:15574495).

Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation (PubMed:16757471, PubMed:22844113).

Biological Process

Ductus arteriosus closure Source: UniProtKB
Female pregnancy Source: UniProtKB
Kidney development Source: Ensembl
Lipoxygenase pathway Source: UniProtKB
Negative regulation of cell cycle Source: UniProtKB
Ovulation Source: UniProtKB
Parturition Source: UniProtKB
Positive regulation of apoptotic process Source: Ensembl
Positive regulation of vascular associated smooth muscle cell proliferation Source: Ensembl
Prostaglandin metabolic process Source: UniProtKB
Regulation of prostaglandin catabolic process Source: UniProtKB
Response to estradiol Source: Ensembl
Response to ethanol Source: Ensembl
Response to lipopolysaccharide Source: Ensembl
Thrombin-activated receptor signaling pathway Source: UniProtKB
Transforming growth factor beta receptor signaling pathway Source: UniProtKB

Cellular Location

Cytoplasm

Involvement in disease

Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (PHOAR1):
A disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.
Cranioosteoarthropathy (COA):
A form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature.
Digital clubbing, isolated congenital (DIGC):
A rare genodermatosis characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx. It is usually symmetrical and bilateral (in some cases unilateral). In nail clubbing usually the distal end of the nail matrix is relatively high compared to the proximal end, while the nail plate is complete but its dimensions and diameter more or less vary in comparison to normal. There may be different fingers and toes involved to varying degrees. Some fingers or toes are spared, but the thumbs are almost always involved.