DAX1

DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) is a is_associated_with::nuclear receptor protein that in humans is encoded by the NR0B1 is_associated_with::gene (nuclear receptor subfamily 0, group B, member 1). The NR0B1 gene is located on the short (p) arm of the is_associated_with::X chromosome between positions 21.3 and 21.2, from is_associated_with::base pair 30,082,120 to base pair 30,087,136.

Function
This gene encodes a protein that lacks the normal is_associated_with::DNA-binding domain contained in other nuclear receptors. The encoded protein acts as a dominant-negative regulator of transcription of other nuclear receptors including is_associated_with::steroidogenic factor 1. This protein also functions as an anti-testis gene by acting antagonistically to is_associated_with::SRY. Mutations in this gene result in both X-linked is_associated_with::congenital adrenal hypoplasia and is_associated_with::hypogonadotropic hypogonadism.

DAX1 plays an important role in the normal development of several hormone-producing tissues. These tissues include the is_associated_with::adrenal glands, the is_associated_with::pituitary gland and is_associated_with::hypothalamus, which are located in the brain, and the male and female reproductive structures (the is_associated_with::testes and ovaries). DAX1 controls the activity of certain genes in the cells that form these tissues during is_associated_with::embryonic development. Proteins that control the activity of other genes are known as transcription factors. DAX1 also plays a role in regulating hormone production in these tissues after they have been formed.

Role in disease
is_associated_with::X-linked adrenal hypoplasia congenita is caused by mutations in the NR0B1 gene. More than 90 NR0B1 mutations that cause X-linked adrenal hypoplasia congenita have been identified. Many of these mutations delete all or part of the NR0B1 gene, preventing the production of DAX1 protein. Some mutations cause the production of an abnormally short protein. Other mutations cause a change in one of the building blocks (amino acids) of DAX1. These mutations are thought to result in a misshapen, nonfunctional protein. Loss of DAX1 function leads to adrenal insufficiency and hypogonadotropic hypogonadism, which are the main characteristics of this disorder.

Duplication of genetic material on the X chromosome in the region that contains the NR0B1 gene can cause a condition called is_associated_with::dosage-sensitive sex reversal. The extra copy of the NR0B1 gene prevents the formation of male reproductive tissues. People who have this duplication usually appear to be female, but are genetically male with both an X and a Y chromosome.

In some cases, genetic material is deleted from the X chromosome in a region that contains several genes, including NR0B1. This deletion results in a condition called is_associated_with::adrenal hypoplasia congenita with complex is_associated_with::glycerol kinase deficiency. In addition to the signs and symptoms of adrenal hypoplasia congenita, individuals with this condition may have elevated levels of lipids in their blood and urine and may have problems regulating blood sugar levels. In rare cases, the amount of genetic material deleted is even more extensive and affected individuals also have is_associated_with::Duchenne muscular dystrophy.

Interactions
DAX1 has been shown to interact with:
 * is_associated_with::COPS2,
 * is_associated_with::NRIP1,
 * is_associated_with::Steroidogenic factor 1, and
 * is_associated_with::SREBF1.