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Genetics Home Reference: your guide to understanding genetic conditions
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SRD5A2

Reviewed April 2008

What is the official name of the SRD5A2 gene?

The official name of this gene is “steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2).”

SRD5A2 is the gene's official symbol. The SRD5A2 gene is also known by other names, listed below.

What is the normal function of the SRD5A2 gene?

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.

How are changes in the SRD5A2 gene related to health conditions?

5-alpha reductase deficiency - caused by mutations in the SRD5A2 gene

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. Other mutations 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 predominantly female, or that are not clearly male or clearly female (sometimes called ambiguous genitalia). Other affected infants have external genitalia that appear predominantly male, 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.

cancers - associated with the SRD5A2 gene

Certain normal variations (polymorphisms) in the SRD5A2 gene may be associated with prostate cancer. Two of these polymorphisms have been studied extensively. The most common variation replaces the amino acid valine with the amino acid leucine at position 89 in steroid 5-alpha reductase 2 (written as Val89Leu or V89L). The other variation replaces the amino acid alanine with the amino acid threonine at position 49 in the enzyme (written as Ala49Thr or A49T). 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. Other studies, however, have not shown these associations. It remains unclear what role SRD5A2 polymorphisms play in prostate cancer risk.

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Studies have shown that somatic SRD5A2 mutations in prostate cancer cells may be associated with the progression of prostate cancer. These mutations may increase the activity of steroid 5-alpha reductase 2, which would raise the levels of DHT in prostate tissue. Research has shown that androgens such as DHT can stimulate prostate cancer growth.

other disorders - associated with the SRD5A2 gene

In women, certain polymorphisms in the SRD5A2 gene may affect the risk of developing a condition called polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess body hair (hirsutism), and weight gain. Some genetic variations increase the activity of steroid 5-alpha reductase 2 in the ovaries, which could contribute to the signs and symptoms of this condition. Other variations, including the common polymorphism Val89Leu, reduce the activity of steroid 5-alpha reductase 2 and are associated with a reduced risk of developing PCOS.

Where is the SRD5A2 gene located?

Cytogenetic Location: 2p23

Molecular Location on chromosome 2: base pairs 31,524,585 to 31,580,970

The SRD5A2 gene is located on the short (p) arm of chromosome 2 at position 23.

The SRD5A2 gene is located on the short (p) arm of chromosome 2 at position 23.

More precisely, the SRD5A2 gene is located from base pair 31,524,585 to base pair 31,580,970 on chromosome 2.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SRD5A2?

You and your healthcare professional may find the following resources about SRD5A2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the SRD5A2 gene or gene products?

  • 5 alpha-SR2
  • MGC138457
  • 3-oxo-5 alpha-steroid 4-dehydrogenase 2
  • S5A2_HUMAN
  • SR type 2
  • steroid 5-alpha-reductase 2
  • Type II 5-alpha reductase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SRD5A2?

acids ; acne ; alanine ; amino acid ; androgens ; cancer ; cell ; chromosome ; deficiency ; dehydrogenase ; DHT ; dihydrotestosterone ; enzyme ; epididymis ; gene ; genitalia ; hirsutism ; hormone ; hypospadias ; inherited ; leucine ; menstruation ; micropenis ; ovary ; polycystic ovary syndrome ; polymorphism ; progression ; prostate ; prostate gland ; protein ; puberty ; scrotum ; semen ; seminal vesicles ; sperm ; syndrome ; testes ; testosterone ; threonine ; tissue ; valine ; vas deferens

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cicek MS, Conti DV, Curran A, Neville PJ, Paris PL, Casey G, Witte JS. Association of prostate cancer risk and aggressiveness to androgen pathway genes: SRD5A2, CYP17, and the AR. Prostate. 2004 Apr 1;59(1):69-76. (http://www.ncbi.nlm.nih.gov/pubmed/14991867?dopt=Abstract)
  • Goodarzi MO, Shah NA, Antoine HJ, Pall M, Guo X, Azziz R. Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab. 2006 Oct;91(10):4085-91. Epub 2006 Jul 18. (http://www.ncbi.nlm.nih.gov/pubmed/16849416?dopt=Abstract)
  • Kim KS, Liu W, Cunha GR, Russell DW, Huang H, Shapiro E, Baskin LS. Expression of the androgen receptor and 5 alpha-reductase type 2 in the developing human fetal penis and urethra. Cell Tissue Res. 2002 Feb;307(2):145-53. Epub 2001 Nov 27. (http://www.ncbi.nlm.nih.gov/pubmed/11845321?dopt=Abstract)
  • Makridakis N, Akalu A, Reichardt JK. Identification and characterization of somatic steroid 5alpha-reductase (SRD5A2) mutations in human prostate cancer tissue. Oncogene. 2004 Sep 23;23(44):7399-405. (http://www.ncbi.nlm.nih.gov/pubmed/15326487?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6716)
  • Ntais C, Polycarpou A, Ioannidis JP. SRD5A2 gene polymorphisms and the risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):618-24. (http://www.ncbi.nlm.nih.gov/pubmed/12869400?dopt=Abstract)
  • Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25-61. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7979239?dopt=Abstract)
  • Salam MT, Ursin G, Skinner EC, Dessissa T, Reichardt JK. Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urol Oncol. 2005 Jul-Aug;23(4):246-53. (http://www.ncbi.nlm.nih.gov/pubmed/16018939?dopt=Abstract)
  • Sasaki G, Ogata T, Ishii T, Kosaki K, Sato S, Homma K, Takahashi T, Hasegawa T, Matsuo N. Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients. J Clin Endocrinol Metab. 2003 Jul;88(7):3431-6. (http://www.ncbi.nlm.nih.gov/pubmed/12843198?dopt=Abstract)
  • Wang Y, Li Q, Xu J, Liu Q, Wang W, Lin Y, Ma F, Chen T, Li S, Shen Y. Mutation analysis of five candidate genes in Chinese patients with hypospadias. Eur J Hum Genet. 2004 Sep;12(9):706-12. (http://www.ncbi.nlm.nih.gov/pubmed/15266301?dopt=Abstract)
  • Wilson JD, Griffin JE, Russell DW. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev. 1993 Oct;14(5):577-93. Review. (http://www.ncbi.nlm.nih.gov/pubmed/8262007?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: August 18, 2014