DOCK2 Gene

The DOCK2 gene (DOC2 stands for "Dedicator Of Cytokinesis 2" is a protein coding gene located on chromosome 5q35.The protein encoded by the DOCK2 gene belongs to the DOCK family of guanine nucleotide exchange factors (GEFs). It is specifically expressed in hematopoietic cells and predominantly in peripheral blood by leukocytes. The protein is involved in the remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling.

The DOCK2 protein activates members of the Rho family of GTPases (GTPases are a large family of hydrolases, enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP)), e.g., RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene lead to immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell numbers and function and also has variable defects in B cell and NK cell function.

Associated pathways include HGF signaling pathway development and factors involved in megakaryocyte development and platelet production.

Diseases associated with DOCK2 include:

• Immunodeficiency 40. "Immunodeficiency 40"( (OMIM: 616433) is an autosomal recessive primary form of combined immunodeficiency (CID) that primarily affects the number and function of T cells. Furthermore, other more variable defects in B cell and NK cell function are found. Patients present with elevated IGE levels, severe invasive bacterial and viral infections in early childhood, and may die without bone marrow transplantation (Dobbs et al. 2015).

1. Dobbs K et al (2015) Inherited DOCK2 deficiency in patients with early-onset invasive infections. New Eng J Med 372: 2409-2422.
2. Sharifinejad N et al (2021) First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature. Allergy Asthma Clin Immunol 17:126.