AKR1C3

Description

The AKR1C3 (aldo-keto reductase family 1 member C3) is a protein-coding gene located on chromosome 10.

Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) or 3α-hydroxysteroid dehydrogenase type 2 (3α-HSD2) is a steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.

== Function == This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin D2, prostaglandin H2, and phenanthrenequinone, and the oxidation of prostaglandin F2α to prostaglandin D2. It is also capable of metabolizing estrogen and progesterone. AKR1C3 may play an important role in the development of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.

== Pathology == AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.

AKR1C3 is a cytosolic enzyme that catalyzes the reduction of ketosteroids to hydroxysteroids using NADH and NADPH. It acts as a reductase on the steroid nucleus and side chain, regulating the metabolism of androgens, estrogens, and progesterone. While it can catalyze both oxidation and reduction in vitro, it likely functions primarily as a reductase in vivo, as its oxidase activity is inhibited by physiological levels of NADPH. AKR1C3 is a key enzyme in the conversion of testosterone from androstenedione. It also reduces prostaglandin D2, progesterone, and estrone. AKR1C3 is involved in inactivating the potent androgen dihydrotestosterone (DHT) by transforming it into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol. AKR1C3 also exhibits retinaldehyde reductase activity toward 9-cis-retinal.

AKR1C3 is also known as DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing