JAG1

The JAG1 gene provides instructions for making a protein called Jagged 1, a component of a fundamental pathway by which cells can signal to each other. The Jagged 1 protein is inserted into the membranes of certain cells. It fits like a key in a lock with other proteins called Notch receptors, which are bound to the membranes of adjacent cells. When the connection is made between the Jagged 1 and Notch proteins, it launches a string of signaling reactions that affect cell functions. The signaling controls how certain types of cells develop in a growing embryo, especially cells destined to be part of the heart, liver, eyes, ears, and spinal column. The Jagged 1 protein continues to play a role throughout life in the development of new blood cells.

Alagille syndrome - caused by mutations in the JAG1 gene

Many different mutations in the JAG1 gene have been identified. A mutated JAG1 gene may provide instructions for making a Jagged 1 protein that is abnormally small or that is the wrong shape because of a change in its amino acid building blocks.

Some mutations change the part of the Jagged 1 protein that protrudes from the cell membrane, affecting its ability to attach to the Notch receptor on an adjacent cell. Other mutations delete the segment of the Jagged 1 protein that normally spans the cell membrane (the transmembrane domain), preventing the protein from finding its proper location in the membrane. These changes disrupt the signaling pathway, causing errors in development that result in missing or narrowed bile ducts in the liver, heart defects, characteristic facial features, and changes in other parts of the body. People with JAG1 mutations may have one or more of these problems, and the type and severity of problems can differ within the same affected family.