SLAMF6 Gene: Function, Expression, and Disease Associations | Biomedical Resource

SLAMF6 (SLAM family member 6) is a type I transmembrane protein belonging to the signaling lymphocytic activation molecule (SLAM) family. It is expressed on hematopoietic cells, particularly T cells, NK cells, and B cells. SLAMF6 acts as a self-ligand receptor, mediating homotypic interactions that modulate immune cell signaling. It contains immunoreceptor tyrosine-based switch motifs (ITSMs) in its cytoplasmic tail, which recruit SH2 domain-containing proteins such as SAP (SH2D1A) and EAT-2 to propagate downstream signals. SLAMF6 plays critical roles in T cell activation, NK cell cytotoxicity, and humoral immunity. Dysregulation of SLAMF6 has been implicated in autoimmune diseases (e.g., systemic lupus erythematosus) and certain cancers, making it a potential therapeutic target.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SLAM family signaling pathway

• T cell receptor signaling pathway

• NK cell mediated cytotoxicity

• Immune system (Reactome)

The SLAMF6 protein (also known as CD352 or NTB-A) is a 331-amino acid type I membrane glycoprotein with an extracellular region containing two immunoglobulin-like domains (V and C2 type) and a cytoplasmic tail with two ITSMs. It is expressed on the surface of T cells, NK cells, B cells, and other hematopoietic cells. SLAMF6 undergoes homophilic interactions (self-ligand) and recruits SH2 domain-containing adaptors, such as SAP and EAT-2, to modulate intracellular signaling. In T cells, SLAMF6 co-stimulates activation and cytokine production; in NK cells, it enhances cytotoxicity. The protein is involved in immune synapse formation and has been implicated in autoimmune and malignant processes. Post-translational modifications include glycosylation, which is essential for ligand binding.