JAK3-deficient severe combined immunodeficiency (SCID) is an inherited disorder of the immune system. Individuals with JAK3-deficient SCID lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with JAK3-deficient SCID are described as opportunistic because they ordinarily do not cause illness in healthy people. Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush, pneumonia, and skin rashes. Persistent illness also causes affected individuals to grow more slowly than other children. Without treatment, people with JAK3-deficient SCID usually live only into early childhood.

JAK3-deficient SCID is caused by mutations in the JAK3 gene. The protein produced from this gene helps regulate the growth and maturation of certain types of white blood cells (lymphocytes) called T cells and natural killer cells. In addition, the JAK3 protein is important for the normal maturation of another type of lymphocyte called B cells. T cells, B cells, and natural killer cells attack bacteria, viruses, and fungi, and help regulate the entire immune system.

Mutations in the JAK3 gene prevent the production of JAK3 protein or lead to production of a nonfunctional protein. A loss of functional JAK3 protein results in the absence of T cells and natural killer cells and a normal number of poorly functioning B cells. This shortage of functional lymphocytes causes people with JAK3-deficient SCID to be susceptible to infections.

Normal Function

The JAK3 gene provides instructions for making a protein that is critical for the normal development and function of the immune system. The JAK3 protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. Signals relayed by the JAK3 protein regulate the growth and maturation of certain types of white blood cells (lymphocytes) called T cells and natural killer cells. In addition, JAK3 is important for the normal maturation of another type of lymphocyte called B cells. T cells, B cells, and natural killer cells attack bacteria, viruses, and fungi and help regulate the entire immune system.

Health Conditions Related to Genetic Changes

JAK3-deficient severe combined immunodeficiency

More than 50 JAK3 gene mutations have been identified in people with JAK3-deficient severe combined immunodeficiency (SCID), an impairment of the immune system that leads to repeated and persistent infections that can be life-threatening.

Most mutations in the JAK3 gene prevent the production of JAK3 protein or result in a protein that is unstable and quickly broken down. Others lead to production of a protein that cannot perform its function. Without functional JAK3 protein, certain chemical signals are not relayed to the nucleus, impairing lymphocyte growth and development. As a result, individuals with JAK3-deficient SCID have few or no T cells and natural killer cells and a normal number of poorly functioning B cells. The shortage of functional lymphocytes causes people with this condition to be susceptible to infections.

Other Names for This Gene

• JAK-3
• JAK3_HUMAN
• JAKL
• Janus kinase 3 (a protein tyrosine kinase, leukocyte)
• L-JAK
• leukocyte Janus kinase
• LJAK
• tyrosine-protein kinase JAK3

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

JAK3-deficient SCID accounts for an estimated 7 to 14 percent of cases of SCID. The prevalence of SCID from all genetic causes combined is approximately 1 in 50,000, although it may be higher in certain regions.