HPGD Gene

The HPGD gene (HPGD stands for 15-hydroxyprostaglandin dehydrogenase) is a protein-coding gene located on chromosome 4q34.1. Several transcript variants encoding different isoforms have been found for this gene.

The HPGD gene encodes a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The encoded enzyme is responsible for the metabolism of prostaglandins, which play a role in a variety of physiological and cellular processes such as inflammation.

Mutations in this gene lead to primary autosomal recessive hypertrophic osteoarthropathy and cranioosteoarthropathy.

Diseases associated with HPGD include:

• Primary hypertrophic osteoarthropathy (autosomal recessive).

The encoded HPGD protein catalyzes the NAD-dependent dehydrogenation (oxidation) of a wide range of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins, and resolvins), producing the corresponding keto (oxo) metabolites. Decreases levels of proproliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer due to increased expression of cyclooxygenase 2) and generates oxo fatty acid products, which can profoundly affect cell function by abrogating the expression of pro-inflammatory cytokines.