CD4 Gene: Function, Expression, Mutations & Clinical Significance

The CD4 gene encodes the CD4 protein, a single-pass type I membrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR) on helper T cells. It is essential for the recognition of antigens presented by MHC class II molecules on antigen-presenting cells. CD4 also functions as the primary high-affinity receptor for the human immunodeficiency virus (HIV), facilitating viral entry into host cells. The protein is composed of four immunoglobulin-like domains (D1-D4), with the D1 domain binding to the beta-2 domain of MHC class II and the gp120 envelope protein of HIV. CD4 is expressed on the surface of helper T cells, regulatory T cells, monocytes, macrophages, and dendritic cells. Its expression is critical for the development and function of the adaptive immune system.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T cell receptor signaling pathway

• HIV lifecycle

• Adaptive Immune System

• PD-1 signaling

• Costimulation by the CD28 family

The CD4 protein is a 458-amino-acid type I transmembrane glycoprotein with a molecular weight of approximately 55 kDa. It consists of four extracellular immunoglobulin-like domains (D1-D4), a single transmembrane region, and a short cytoplasmic tail. The D1 domain is critical for binding to MHC class II molecules and HIV gp120. The cytoplasmic tail interacts with the tyrosine kinase Lck, which is essential for TCR signaling. CD4 is expressed on helper T cells, regulatory T cells, monocytes, macrophages, and dendritic cells. It plays a central role in the adaptive immune response by stabilizing the TCR-MHC class II interaction and enhancing T-cell activation. As the primary receptor for HIV, CD4 is a major target for therapeutic interventions, including monoclonal antibodies (e.g., ibalizumab) and entry inhibitors.