[5] It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins.

Despite the fact that little is known about the cellular role of Dock8 its importance has been highlighted in several studies which have identified disruption of the DOCK8 gene in disease.

Deletion and reduced expression of Dock8 have been reported in a human lung cancer cell line[8] and Dock8 was also identified as a putative candidate gene associated with progression of gliomas.

This variant of Hyperimmunoglobulin E syndrome (HIES) was first described in 2004 [10] and this clinical entity is known to be due to having biallelic germline mutations in the DOCK8 gene.

Nearly all patients have recurrent or chronic upper and lower respiratory tract infections, with many requiring sinus surgery and myringotomy tube placement.

[11] Once a diagnosis is made, treatment is based on an individual's clinical condition and may include medication and other strategies for managing infections, allergies, and asthma.

Hematopoietic stem cell transplant is curative in many primary immunodeficiencies and has successfully been used for patients with DOCK8 immunodefiency.