MED12

The MED12 gene provides instructions for making a protein called mediator complex subunit 12. As its name suggests, this protein forms one part (subunit) of the mediator complex, which is a group of about 25 proteins that work together to regulate gene activity. The mediator complex physically links transcription factors, which are proteins that influence whether genes are turned on or off, with an enzyme called RNA polymerase II. This enzyme initiates gene transcription, the process by which information stored in a gene's DNA is used to build proteins.

Researchers believe that the MED12 protein is involved in many aspects of early development, including the development of nerve cells (neurons) in the brain. The MED12 protein is part of several chemical signaling pathways within cells. These pathways help direct a broad range of cellular activities, such as cell growth, cell movement (migration), and the process by which cells mature to carry out specific functions (differentiation).

FG syndrome - caused by mutations in the MED12 gene

Researchers have identified a mutation in the MED12 gene in a small percentage of people with FG syndrome. This mutation changes a single protein building block (amino acid) in the MED12 protein. Specifically, it replaces the amino acid arginine with the amino acid tryptophan at protein position 961 (written as Arg961Trp or R961W). This mutation alters the structure of the MED12 protein, which likely disrupts its ability to regulate gene activity during development. However, it is unclear how this change leads to intellectual disability, behavioral changes, and the physical features associated with FG syndrome.

other disorders - associated with the MED12 gene

Another mutation in the MED12 gene has been found to cause Lujan-Fryns syndrome, a disorder characterized by intellectual disability; tall stature with long, thin fingers and toes; and a long, narrow face. The mutation responsible for Lujan-Fryns syndrome replaces the amino acid asparagine with the amino acid serine at position 1007 of the MED12 protein (written as Asn1007Ser or N1007S). Although this change alters the structure of the MED12 protein, it is unclear how it causes the specific features of this syndrome.

A particular variation (polymorphism) in the MED12 gene has been associated with a modestly increased risk of schizophrenia in people of northern European ancestry. This variation is an insertion of four extra amino acids in the MED12 protein. Because this protein is involved in several different signaling pathways, it has been difficult to determine the effects of the variation on brain function. This variation is among many factors under study to help explain the causes of schizophrenia. A large number of genetic and lifestyle factors, most of which remain unknown, likely determine the risk of developing this condition.