AKT1

At least one mutation in the AKT1 gene has been found to cause Proteus syndrome, a rare condition characterized by overgrowth of the bones, skin, and other tissues. This mutation changes a single protein building block (amino acid) in AKT1 kinase. Specifically, it replaces the amino acid glutamic acid with the amino acid lysine at protein position 17 (written as Glu17Lys or E17K). The mutation is not inherited from a parent; in people with Proteus syndrome, the mutation arises randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.

The Glu17Lys mutation leads to the production of an overactive AKT1 kinase that is turned on when it should not be. The abnormally active protein disrupts a cell's ability to regulate its own growth, allowing the cell to grow and divide abnormally. Increased cell proliferation in various tissues and organs leads to the overgrowth characteristic of Proteus syndrome. Studies suggest that the AKT1 gene mutation is more common in groups of cells that experience overgrowth than in the parts of the body that grow normally.

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The Glu17Lys mutation in the AKT1 gene (described above) has also been found in a small percentage of breast, ovarian, and colorectal cancers. In these cases the mutation is somatic, which means it is acquired during a person's lifetime and is present only in tumor cells. The mutation abnormally activates AKT1 kinase, allowing cells to grow and divide without control or order. This disordered cell proliferation leads to the development of cancerous tumors.

Although the Glu17Lys mutation has been reported in only a few types of cancer, increased activity (expression) of the AKT1 gene is found in many types of cancer.

Several common variations (polymorphisms) in the AKT1 gene have been found more often in people with schizophrenia than in those without the disease. These polymorphisms alter single DNA building blocks (nucleotides) in the AKT1 gene. It is unknown whether the genetic changes have an effect on the structure or function of AKT1 kinase, and if so, how they are related to the development of schizophrenia. AKT1 gene polymorphisms appear to be one of many genetic and environmental factors that contribute to the development of this complex psychiatric disorder.