Adhesion G protein-coupled receptor E2 (ADGRE2) (ADGRE2)

Adhesion G protein-coupled receptor E2 (ADGRE2), also known as CD312, is a member of the adhesion class of G protein-coupled receptors primarily expressed on the surface of myeloid cells, including granulocytes, monocytes, and mast cells (UniProt Q9UHX3). It is characterized by a large extracellular domain containing epidermal growth factor (EGF)-like modules that facilitate cell-cell and cell-matrix interactions, non-covalently linked to a seven-transmembrane signaling domain (Boyden et al., NEJM, 2016). ADGRE2 functions as a mechanosensor; a specific missense mutation in the receptor's autoproteolysis induction domain is known to cause vibratory urticaria, where physical vibration triggers mast cell degranulation and subsequent allergic response (Boyden et al., NEJM, 2016). In the field of oncology, ADGRE2 has emerged as a significant therapeutic target for acute myeloid leukemia (AML) because it is highly expressed on leukemic blasts and leukemic stem cells but absent from normal hematopoietic stem cells (Kim et al., Blood, 2017). Current research is focused on developing ADGRE2-targeted therapies, such as chimeric antigen receptor (CAR) T-cells and monoclonal antibodies, to selectively eliminate malignant myeloid cells (Kim et al., Blood, 2017; Kwong et al., 2020). However, therapeutic development must carefully manage the risk of systemic mast cell activation and potential off-target effects on healthy myeloid populations (Boyden et al., NEJM, 2016).

Other names

CD312EMR2EGF-like module-containing mucin-like hormone receptor-like 2

Targeted cell depletion via antibody-dependent cellular cytotoxicity (ADCC) or CAR-T cell-mediated lysis; modulation of mechanosensitive signaling pathways (Boyden et al., NEJM, 2016; Kim et al., Blood, 2017).