GPR56

The GPR56 gene provides instructions for making a protein that is critical for normal brain development. Before birth, the GPR56 protein appears to be essential for the normal growth and movement (migration) of nerve cells (neurons) in a part of the brain called the cerebral cortex. This outer layer of the brain carries out many important functions, such as sensation, voluntary muscle movement, thought, planning, and memory.

Although the GPR56 protein has been studied most extensively in the brain, it is active in many of the body's tissues. The GPR56 protein interacts with other proteins on the cell surface to trigger a series of chemical signals within the cell. Studies suggest that GPR56 signaling may play an important role in attaching cells to one another (cell adhesion).

polymicrogyria - caused by mutations in the GPR56 gene

At least eleven mutations in the GPR56 gene have been identified in people with a severe form of polymicrogyria called bilateral frontoparietal polymicrogyria (BFPP). This disorder causes intellectual disability, delayed development, problems with speech and movement, and recurrent seizures (epilepsy). Most of the identified mutations change a single protein building block (amino acid) in the GPR56 protein. These mutations interfere with the normal processing of the protein. The abnormal protein becomes trapped within the cell, where it is unable to reach the cell surface to carry out its normal signaling functions.

A loss of GPR56 function likely disrupts the normal migration of neurons in the developing brain. As a result, certain regions of the cerebral cortex—areas known as the frontal and parietal lobes—develop too many folds (called gyri), and the folds are unusually small. These brain abnormalities cause intellectual disability and the other neurological problems associated with bilateral frontoparietal polymicrogyria.