SIX1

The SIX1 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 SIX1 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, the kidneys, the nose, an immune system gland called the thymus, and muscles used for movement (skeletal muscles).

branchiootorenal syndrome - caused by mutations in the SIX1 gene

At least four mutations in the SIX1 gene are known to cause the features of branchiootorenal (BOR) syndrome. In some families with SIX1 mutations, researchers have identified the condition as branchiooto (BO) syndrome. Branchiooto syndrome includes many of the same features as branchiootorenal syndrome, but affected individuals do not have kidney (renal) malformations. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome).

Each of the known SIX1 mutations changes a single protein building block (amino acid) in the SIX1 protein. Some of these mutations prevent the SIX1 protein from interacting with other proteins, such as EYA1. Other mutations also affect the ability of SIX1 protein to bind to DNA. Both of these functions are needed for the SIX1 protein to regulate gene activity during embryonic development. When the SIX1 protein is faulty, it 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.