DOCK8 gene
The DOCK8 gene encodes a protein essential for the survival, structure, and movement of immune system cells.
Normal Function
The DOCK8 gene provides instructions for a member of the DOCK family of proteins, which act as guanine nucleotide exchange factors (GEFs). GEFs activate GTPases, which regulate the structural framework inside cells (the cytoskeleton). By controlling the cytoskeleton, these proteins influence cell structure and movement (migration).
DOCK8 is found most abundantly in immune system cells, including T cells, NK cells, and B cells. It helps maintain the structure and integrity of these cells and aids in their movement to sites of infection, particularly the skin. It also participates in signaling pathways that stimulate B cells to mature and produce antibodies.
Health Conditions Related to Genetic Changes
DOCK8 immunodeficiency syndrome
More than 130 mutations in the DOCK8 gene cause DOCK8 immunodeficiency syndrome (also called autosomal recessive hyper-IgE syndrome or AR-HIES). This disorder causes:
- Recurrent severe infections of the skin and respiratory tract
- Allergies, including food and environmental allergies
- Asthma
- An inflammatory skin disorder called eczema
Most mutations involve deletions of DNA, leading to a shortage or total absence of functional DOCK8 protein. This impairs immune cell development and function. Specifically, T cells lacking DOCK8 cannot maintain their shape when moving through dense spaces like the skin, causing them to die prematurely. The shortage of these cells and impaired B cell maturation weaken the immune response. Additionally, the condition is associated with higher-than-normal production of immunoglobulin E (IgE), which contributes to allergic reactions.
Other Names for This Gene
- 1200017A24Rik
- dedicator of cytokinesis protein 8 isoform 1
- dedicator of cytokinesis protein 8 isoform 2
- dedicator of cytokinesis protein 8 isoform 3
- epididymis luminal protein 205
- FLJ00026
- FLJ00152
- FLJ00346
- HEL-205
- MRD2
- ZIR8