CD247 Gene

The protein encoded by this gene (chromosome 1q24.2) is the T cell receptor zeta, which together with the T cell receptor alpha/beta and gamma/delta heterodimers and CD3-gamma, -delta and -epsilon forms the T cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to multiple intracellular signal transduction pathways. Low expression of the antigen leads to impaired immune response. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.

CD247 (CD247 molecule) is a protein coding gene. Diseases associated with CD247 include Immunodeficiency 25 and T-B+ Severe Combined Immunodeficiency Due To Cd3delta/Cd3epsilon/Cd3zeta. Related pathways include the phospholipase C pathway and the ICos-ICosL pathway in T helper cells. Gene Ontology (GO) annotations associated with this gene include protein homodimerization activity and transmembrane signaling receptor activity.

CD247 is part of the TCR-CD3 complex on the surface of T lymphocytes, which plays an essential role in the adaptive immune response. When antigen-presenting cells (APCs) activate the T cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G, and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR binding, these motifs are phosphorylated by the Src family protein tyrosine kinases LCK and FYN, leading to activation of downstream signaling pathways. CD3Z-ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70, leading to phosphorylation of ZAP70 and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T cell differentiation. Also involved in activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN)

Mutations in the CD245 gene are associated with immunodeficiency 25 syndrome.

1. Alarcon B et al (1988) Familial defect in the surface expression of the T-cell receptor-CD3 complex. New Eng. J Med 319: 1203-1208.
2. Arnaiz-Villena A et al.(1991) iochemical basis of a novel T lymphocyte receptor immunodeficiency by immunohistochemistry: a possible CD3-gamma abnormality. Lab Invest 64: 675-681.
3. Rieux-Laucat F et al (2006) Inherited and somatic CD3-zeta mutations in a patient with T-cell deficiency. New Eng J Med 354: 1913-1921.
4. Asgardoon MH et al (2020). Monogenic primary immunodeficiency disorder associated with common variable immunodeficiency and autoimmunity. Int Arch Allergy Immunol 181:706-714.