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Target intelligence / Profile preview
Membrane-spanning 4-domains subfamily A member 4A (MS4A4A)
- Target
- MS4A4A
- Molecular classification
- Tetraspanin-like protein, Four-transmembrane domain protein (tetraspanning), Membrane protein, Other (not a classic receptor, ion channel, or enzyme but regulates signaling)
01
Overview
Membrane-spanning 4-domains subfamily A member 4A (MS4A4A) is a tetraspanning transmembrane protein of the MS4A gene family, predominantly expressed in myeloid immune cells, especially macrophages and mast cells. MS4A4A facilitates receptor trafficking, regulates the formation of signaling complexes in lipid rafts (including dectin-1 and FcεRI), and is upregulated during macrophage differentiation, particularly into the M2 anti-inflammatory phenotype. Its expression is induced by glucocorticoid hormones and is seen in tissue macrophages in settings such as COVID-19 and rheumatoid arthritis. MS4A4A is under investigation as a prognostic marker in cancers due to its association with immune cell infiltration in tumors and may serve as a biomarker for immune modulation and tissue homeostasis. No approved drugs directly target this protein[1][2][3].
- Other names
- MS4A4ACD20L14SPAN1CD20 antigen-like 1Four-span transmembrane protein 1HDCME31PMS4A4MS4A7Fc epsilon receptor beta subunit homolog (some aliases may overlap with closely related MS4A family members but are commonly used for MS4A4A)
02
Mechanism of action
Not applicable (no direct-drug mechanism established; protein itself modulates receptor trafficking and signaling, which could be targeted indirectly)
03
Biological functions
Receptor trafficking (facilitates endocytic recycling of other receptors, e.g., KIT tyrosine kinase)Signal transduction (regulates signaling complexes such as dectin-1 and FcεRI; interacts with lipid rafts)Regulation of immune cell differentiation (upregulated during monocyte-to-macrophage differentiation, especially in M2 macrophages)Modulation of mast cell activation (IgE-mediated)Effector molecule production (supports NK cell–mediated metastasis control)
04
Disease associations
Cancer (marker of immune cell infiltration and potential prognostic indicator)Inflammation (regulates macrophage and mast cell signaling)Infection (expressed in tissue macrophages from COVID-19 patients)Other immune disorders (potentially relevant in rheumatoid arthritis and allergic conditions due to mast cell involvement)
05
Safety considerations
No major safety concerns specified for direct targeting.Potential challenges include specificity (due to MS4A gene family homology), off-target effects in macrophages, and immune modulation risks if used for therapy
06
Biomarkers
Marker for M2 macrophages in tissue and tumors (including cancer settings)Marker for immune cell infiltration and differentiation (monocyte-to-macrophage progression)
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