SRD5A2 Gene: Function, Mutations, and Associated Diseases

The SRD5A2 gene encodes steroid 5 alpha-reductase 2, an enzyme that catalyzes the conversion of testosterone to the more potent androgen dihydrotestosterone (DHT). This enzyme is primarily expressed in androgen-sensitive tissues such as the prostate, seminal vesicles, and external genitalia. SRD5A2 plays a critical role in male sexual differentiation during embryonic development and in the maintenance of prostate function in adults. Loss-of-function mutations cause 5α-reductase 2 deficiency, a disorder of sexual development. Polymorphisms in SRD5A2 have been associated with benign prostatic hyperplasia and prostate cancer risk.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Androgen biosynthesis (Reactome: R-HSA-196015)

• Metabolism of steroids (Reactome: R-HSA-8957322)

• Prostate cancer (KEGG: hsa05215)

Steroid 5 alpha-reductase 2 is a 254-amino acid microsomal enzyme with a molecular weight of approximately 28 kDa. It contains a NADPH-binding domain and a steroid-binding domain. The enzyme reduces the double bond at the 4-5 position of testosterone to form DHT. It is anchored in the endoplasmic reticulum membrane via four transmembrane helices. The protein is highly expressed in the prostate and male reproductive tissues. Structural studies have identified key residues (e.g., Gly203, Arg246) essential for catalytic activity.