OCA2

The OCA2 gene (formerly called the P gene) provides instructions for making a protein called the P protein. This protein is located in melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. Melanin is also found in the light-sensitive tissue at the back of the eye (the retina), where it plays a role in normal vision.

Although the exact function of the P protein is unknown, it is essential for normal pigmentation and is likely involved in the production of melanin. Within melanocytes, the P protein may transport molecules into and out of structures called melanosomes (where melanin is produced). Researchers believe that this protein may also help regulate the relative acidity (pH) of melanosomes. Tight control of pH is necessary for most biological reactions to proceed properly.

oculocutaneous albinism - caused by mutations in the OCA2 gene

More than 60 mutations in the OCA2 gene have been identified in people with oculocutaneous albinism type 2. People with this form of albinism often have light yellow, blond, or light brown hair, creamy white skin, light-colored eyes, and problems with vision. The most common OCA2 mutation is a large deletion in the gene, which is found in many affected individuals of sub-Saharan African heritage. Other OCA2 mutations, including changes in single DNA building blocks (base pairs) and small deletions, are more common in other populations. Mutations in the OCA2 gene disrupt the normal production of melanin, which reduces coloring of the hair, skin, and eyes and affects vision.

Angelman syndrome - associated with the OCA2 gene

Some people with Angelman syndrome have unusually light-colored hair and fair skin, which are thought to be caused by a loss of one copy of the OCA2 gene in each cell. This gene is located in a region of chromosome 15 that is often deleted in individuals with Angelman syndrome. Cells with only one copy of the OCA2 gene make a reduced amount of P protein, which affects the coloring of skin and hair.

A small percentage of people with Angelman syndrome also have oculocutaneous albinism type 2. In addition to a deletion in one copy of chromosome 15 (which causes the features of Angelman syndrome), these people have a mutation in the OCA2 gene on the other copy of chromosome 15. As a result, cells make little or no functional P protein. A lack of P protein disrupts the production of melanin, leading to the characteristic features of albinism.

Prader-Willi syndrome - associated with the OCA2 gene

Like people with Angelman syndrome, some individuals with Prader-Willi syndrome have unusually fair skin and light-colored hair because they have lost one copy of the OCA2 gene in each cell. The region of chromosome 15 containing the OCA2 gene is often deleted in individuals with Prader-Willi syndrome. Cells missing a copy of the OCA2 gene make less P protein than cells with two functional copies of the gene, leading to light-colored skin and hair.

Oculocutaneous albinism type 2 also has been found in a small number of people with Prader-Willi syndrome. These people have a deletion in one copy of chromosome 15 (which causes the features of Prader-Willi syndrome) along with a mutation in the OCA2 gene on the other copy of chromosome 15. This combination of genetic changes leaves no functional copies of the gene, resulting in an absence of P protein.