SIX5

The SIX5 gene is part of a group of similar genes known as the SIX gene family. Genes in this family provide instructions for making proteins that bind to DNA and control the activity of other genes. Based on this role, SIX proteins are called transcription factors.

The SIX5 protein interacts with several other proteins, including the EYA1 protein, to regulate the activity of genes that are important for normal development. Before birth, these protein interactions appear to be essential for the normal formation of many tissues, including the second branchial arch (a structure that gives rise to tissues in the front and side of the neck), the ears, and the kidneys. Researchers have also found the SIX5 protein in the adult brain, heart, eyes, and muscles used for movement (skeletal muscles).

branchiootorenal syndrome - caused by mutations in the SIX5 gene

At least four mutations in the SIX5 gene have been found in people with branchiootorenal (BOR) syndrome. Each of these mutations changes a single protein building block (amino acid) in the SIX5 protein, which prevents SIX5 from interacting with the EYA1 protein effectively. Because this protein interaction is necessary for the activation of certain genes during embryonic development, the altered SIX5 protein disrupts the normal development of many tissues before birth. The major signs and symptoms of branchiootorenal syndrome result from abnormal development of the second branchial arch, ears, and kidneys.