MAM domain-containing glycosylphosphatidylinositol anchor protein 2 (MDGA2)

MDGA2 (MAM domain-containing glycosylphosphatidylinositol anchor protein 2) is a cell adhesion molecule of the immunoglobulin superfamily with roles in neural development, synapse organization, and the regulation of excitation-inhibition balance in the brain[1][2][3][4]. It is anchored to the postsynaptic membrane via a C-terminal GPI anchor and contains six immunoglobulin-like domains, a fibronectin type III domain, and a MAM domain critical for protein-protein interactions such as binding to neuroligins and TrkB[3]. MDGA2 serves as a negative regulator of excitatory synaptic transmission, interacting with key postsynaptic proteins and modulating social behavior and neurodevelopmental phenotypes; genetic variants or aberrant methylation are implicated in autism spectrum disorder, schizophrenia, gastric cancer, and lupus[2][3][4][5]. No drugs directly target MDGA2 in clinical practice, but experimental MDGA2-derived peptides and small molecule TrkB inhibitors show promise in correcting synaptic and behavioral deficits in preclinical models[3]. The gene is located on chromosome 14, with homologues in rat and mouse, and is expressed in restricted neural populations[1].

Other names

MDGA2MAMDC1MAM domain-containing protein 1c14_5286UNQ8188/PRO23197MDGA2_HUMAN

Inhibition/blocking of BDNF-TrkB signaling via disruption of TrkB interaction using MDGA2-derived peptides or small molecules. Modulation of postsynaptic response (mainly AMPA and NMDA receptor-mediated transmission). Synaptic suppression (limiting excitatory synapse formation/function).