ZAP70

The ZAP70 gene provides instructions for making a protein called zeta-chain-associated protein kinase. This protein is part of a signaling pathway that directs the development of and turns on (activates) immune system cells called T cells. T cells identify foreign substances and defend the body against infection.

The ZAP70 gene is important for the development and function of several types of T cells. These include cytotoxic T cells (CD8+ T cells), whose functions include destroying cells infected by viruses. The ZAP70 gene is also involved in the activation of helper T cells (CD4+ T cells). These cells direct and assist the functions of the immune system by influencing the activities of other immune system cells.

ZAP70-related severe combined immunodeficiency - caused by mutations in the ZAP70 gene

More than 12 mutations in the ZAP70 gene have been identified in people with ZAP70-related severe combined immunodeficiency (SCID). These mutations either change single protein building blocks (amino acids) in the protein sequence or disrupt how genetic information is pieced together to make the blueprint for producing the protein.

Mutations in the ZAP70 gene prevent the production of zeta-chain-associated protein kinase or result in a protein that is unstable and cannot perform its function. A loss of functional zeta-chain-associated protein kinase leads to the absence of CD8+ T cells and an excess of inactive CD4+ T cells. The resulting shortage of active T cells causes people with ZAP70-related SCID to be more susceptible to infection.