TBX5

The TBX5 gene provides instructions for making a protein called T-box 5, which is part of the T-box family. Proteins in the T-box family play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, T-box proteins function as transcription factors. Transcription factors enter the cell nucleus and bind to specific regions of DNA. By attaching to critical DNA regions, transcription factors help control the activity of particular genes. Transcription factors in the T-box family share a similar protein segment, called the T-box, that attaches to DNA. T-box proteins can also interact with other transcription factors in the T-box family or with transcription factors in other protein families.

During embryonic development, the T-box 5 protein turns on (activates) genes involved in the normal development of the arm and hand (upper limb). The T-box 5 protein also activates genes that play an important role in the growth and development of the heart. This protein appears to be particularly important for the formation of the wall (septum) that separates the right and left sides of the heart.

Holt-Oram syndrome - caused by mutations in the TBX5 gene

Researchers have identified more than 30 mutations that cause Holt-Oram syndrome. Most of these mutations prevent the production of the T-box 5 protein. Some mutations change one of the building blocks (amino acids) used to make the T-box 5 protein. Researchers believe that a change in amino acids impairs the protein's ability to bind to DNA. As a result of TBX5 mutations, genes that are important for development of the heart and upper limbs are probably not activated. Abnormal development of the heart and upper limbs is characteristic of Holt-Oram syndrome.