The DAX1 gene is a member of the nuclear hormone receptor family. However, the ligand for this receptor is unknown, making it an orphan receptor. DAX-1 mutations are primarily associated with the X-linked form of Congenital Adrenal Hypoplasia. In addition, several other related phenotypes, such as isolated mineralocorticoid insufficiency, premature sexual development, and/or primary adrenal insufficiency in 46, XX patients have also been reported with defects in DAX1. Duplication of DAX1 is associated with an XY sex-reversed phenotype.
The mechanism of action of the DAX1 protein is not clearly understood. But it is hypothesized that the receptor plays a role as a co-regulatory protein that inhibits the transcriptional activity of other nuclear receptors. It also appears to function as an antitestis gene by acting antagonistically to the sex-determining region. Recent evidence also indicates that the DAX1 protein may act as a negative coregulator of some estrogen receptors, liver receptor homologue-1, androgen and progesterone receptors, and may also function as a negative regulator of steroidogenesis.