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SRD5A2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SRD5A2 gene

The SRD5A2 gene provides instructions for making an enzyme essential for male sexual development and is associated with conditions like 5-alpha reductase deficiency and prostate cancer.

Normal Function

The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to a more potent androgen, dihydrotestosterone (DHT), in male reproductive tissues.

Testosterone and DHT are essential for the normal development of male sex characteristics. Before birth, testosterone is responsible for the formation of internal male genitalia, including the tubes that collect sperm and carry it out of the testes (the epididymis and vas deferens) and glands that help produce semen (the seminal vesicles). DHT directs the development of the external genitalia, including the penis and scrotum, and the prostate gland. During puberty, these two hormones also play an important role in the development of male secondary sex characteristics such as the growth of facial and body hair, increased muscle mass, and deepening of the voice.

Health Conditions Related to Genetic Changes

5-alpha reductase deficiency

About 50 mutations in the SRD5A2 gene have been identified in people with 5-alpha reductase deficiency. Most of these mutations change single protein building blocks (amino acids) in steroid 5-alpha reductase 2. Some of these genetic changes render the enzyme completely inactive, while others reduce but do not eliminate the enzyme's function.

As a result of SRD5A2 mutations, the body cannot effectively convert testosterone to DHT in reproductive tissues. A shortage of DHT disrupts the formation of external genitalia before birth. People with 5-alpha reductase deficiency are genetically male, with one X and one Y chromosome in each cell, but they may be born with external genitalia that look female-typical, or that are not clearly male or clearly female. Other affected infants have external genitalia that appear male-typical, but they often have an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).

During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty.

Prostate cancer

Certain normal variations (polymorphisms) in the SRD5A2 gene may be associated with prostate cancer. Two of these polymorphisms have been studied extensively:

  • Val89Leu (V89L): Replaces the amino acid valine with leucine at position 89.
  • Ala49Thr (A49T): Replaces the amino acid alanine with threonine at position 49.

Some studies have suggested that these variations are associated with an increased risk of developing prostate cancer or having a more aggressive form of the disease, though other studies have not shown these associations. It remains unclear what role SRD5A2 polymorphisms play in prostate cancer risk.

Additionally, somatic SRD5A2 mutations—which are acquired during a person's lifetime and present only in certain cells—may be associated with the progression of prostate cancer. These mutations may increase the activity of steroid 5-alpha reductase 2, raising levels of DHT in prostate tissue, which can stimulate prostate cancer growth.

Other disorders

In women, certain polymorphisms in the SRD5A2 gene may affect the risk of developing polycystic ovary syndrome (PCOS). Some genetic variations increase the activity of steroid 5-alpha reductase 2 in the ovaries, which could contribute to signs such as irregular menstruation, acne, excess body hair (hirsutism), and weight gain. Other variations, including the common polymorphism Val89Leu, reduce the activity of the enzyme and are associated with a reduced risk of developing PCOS.

Frequently Asked Questions

In individuals with significant SRD5A2 mutations, the body cannot convert testosterone to dihydrotestosterone (DHT) effectively. Since DHT is the primary hormone responsible for the development of external male genitalia, its absence leads to ambiguous genitalia at birth. This can range from a small penis (micropenis) to a condition where the external appearance resembles female genitalia, such as a clitoris-like structure and fused labia, even though the individual has testes and male internal organs. The severity of the ambiguity depends on the level of residual enzyme activity. Can individuals with 5-alpha reductase deficiency develop male secondary sex characteristics during puberty?::Yes, a hallmark of 5-alpha reductase deficiency is the development of male secondary sex characteristics at puberty. As the body produces higher levels of testosterone during puberty, these levels are sufficient to drive changes such as muscle growth, deepening of the voice, and growth of facial and body hair, even without adequate DHT. Additionally, some individuals may experience a further masculinization of the external genitalia during puberty, which can sometimes lead to a change in gender identity or social role, particularly in cultures where this condition is recognized. What is the difference between the roles of testosterone and DHT in male development?::Testosterone is primarily responsible for the development of internal male reproductive structures, such as the epididymis, vas deferens, and seminal vesicles, as well as the testes themselves. In contrast, DHT is the more potent androgen that drives the development of external genitalia, including the penis, scrotum, and prostate gland. While both hormones are essential for normal male sexual development, they have distinct targets; a deficiency in DHT specifically impacts external structures, whereas testosterone levels may remain normal or even elevated in response to the lack of DHT feedback. How is 5-alpha reductase deficiency diagnosed in a child with ambiguous genitalia?::Diagnosis typically involves a combination of clinical evaluation and laboratory testing. Doctors will perform karyotyping to confirm the presence of two X chromosomes (46,XX) or two Y chromosomes (46,XY); in this condition, the child will have a 46,XY karyotype. Hormone levels are measured to assess testosterone and DHT ratios; a low DHT to testosterone ratio is suggestive of the deficiency. Definitive diagnosis is achieved through genetic testing that identifies mutations in the SRD5A2 gene. Ultrasound may also be used to locate the testes, which are often undescended in these individuals.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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