the CYP21P1 pseudogene and the complexity of the locus, it is difficult to study the CYP21A2 gene at the molecular level. Clinical significance Congenital adrenal hyperplasia Genetic variants in the CYP21A2 gene cause a disturbance in the development of the enzyme, leading to congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Gene conversion events involving the functional gene and the pseudogene account for many cases of steroid 21-hydroxylase deficiency. CAH is an autosomal recessive disorder. There are multiple forms of CAH, broken down into classical and nonclassical forms based on the amount of enzyme function retained. The classical forms occur in approximately 1 in to 1 in births globally, and include the salt-wasting and simple-virilizing forms. Complete loss of enzymatic activity causes the salt-wasting form. Variations in the structure of 21-hydroxylase are related to the clinical severity of congenital adrenal hyperplasia. Cortisol and aldosterone deficits are associated with life-threatening salt-loss (hence salt-wasting), as the steroids play roles in regulating sodium homeostasis. Simple-virilizing CAH patients (~1-2% enzyme function) maintain adequate sodium homeostasis, but exhibit other symptoms shared by the salt-wasting form, including accelerated growth in childhood and ambiguous genitalia in female neonates. The nonclassical form is the mildest one, retaining about 20% to 50% of enzyme function. This form is associated with mild and clinically silent cortisol impairment, but an excess of androgens post-puberty. Non-classic congenital adrenal hyperplasia Non-classical congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (NCCAH) is a milder and late-onset congenital adrenal hyperplasia. Its prevalence rate in different ethnic groups varies from 1 in to 1 in . Some people affected by the condition have no relevant signs and symptoms, while others experience symptoms of hyperandrogenism. Women with NCCAH usually have normal female genitalia at birth. In later life, the signs and symptoms of the condition may include acne, hirsutism, male-pattern baldness, irregular menstruation, and infertility. Fewer studies have been published about males with NCCAH comparing to those about females, because males are generally asymptomatic. Males, however, may present with acne and early balding. While symptoms are usually diagnosed after puberty, children may present with premature adrenarche. Research on other conditions There is ongoing research on how Genetic variants in the CYP21A2 gene may lead do pathogenic conditions. A variant of this gene has been reported to cause autosomal dominant posterior polar cataract, suggesting that 21-hydroxylase may be involved in the extraadrenal biosynthesis of aldosterone and cortisol in the