SMAD4

SMAD4 provides instructions for making a protein involved in transmitting biochemical signals from the cell membrane to the nucleus. This type of signaling pathway allows the environment outside the cell to affect how the cell produces other proteins. Specifically, the SMAD4 protein is involved in transmitting signals to the cell nucleus from a family of growth factors called transforming growth factor beta proteins, which come from outside the cell and attach to receptors on the cell surface. By regulating the action of these growth factors, the SMAD4 protein serves as a tumor suppressor. Tumor suppressors keep cells from growing and dividing too fast or in an uncontrolled way.

hereditary hemorrhagic telangiectasia - caused by mutations in the SMAD4 gene

Certain mutations in the SMAD4 gene cause juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome. People with this disorder have the blood vessel problems associated with hereditary hemorrhagic telangiectasia as well as an increased risk of developing intestinal growths (polyps), which may become cancerous, at an early age.

SMAD4 mutations affect the signaling pathway of transforming growth factor beta proteins. Disruption of this pathway may interfere both with the tumor suppressor function of SMAD4 and the appropriate development of the boundaries between veins and arteries, resulting in the signs and symptoms of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome.

cancers - increased risk from variations of the SMAD4 gene

People with mutations in the SMAD4 gene appear to have an increased risk of developing various cancers. Some gene mutations are inherited, while others are acquired during a person's lifetime. Such acquired (somatic) mutations are present only in certain cells. Cells with mutations in the SMAD4 gene, whether inherited or somatic, may proliferate out of control and result in a tumor, often in the colon or pancreas.

other disorders - caused by mutations in the SMAD4 gene

Approximately one-fifth of people who have juvenile polyposis syndrome without symptoms of hereditary hemorrhagic telangiectasia have mutations in the SMAD4 gene. These mutations cause the production of SMAD4 proteins that cannot fulfill their tumor suppressor function, resulting in an increased risk of developing intestinal polyps at an early age.