Megakaryocyte and platelet inhibitory receptor G6b (MPIG6B)

Megakaryocyte and platelet inhibitory receptor G6b (MPIG6B) is a glycosylated, plasma membrane-bound cell surface receptor in the immunoglobulin superfamily, encoded within the major histocompatibility complex (MHC) class III region[1][7]. The full-length (canonical) isoform, G6b-B, contains an extracellular Ig-like domain, a transmembrane region, and a cytoplasmic tail with two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which mediate its inhibitory function. Upon phosphorylation, these motifs bind the phosphatases SHP-1 and SHP-2, leading to attenuation of signaling downstream of key platelet activation receptors. G6b-B thus acts as a crucial regulator of platelet production, megakaryocyte function, and platelet aggregation, and is essential for maintaining normal hemostasis. Genetic defects or dysregulation of this receptor have been associated with hematologic disorders such as thrombocytopenia, anemia, and myelofibrosis[1][3][7]. G6b-B binds heparin with high affinity, though the physiological significance of this interaction is still under investigation[2]. There are no current approved drugs directly targeting MPIG6B, but its key role in platelet inhibition has led to interest in its potential as an antithrombotic drug target[3].

Other names

C6orf25G6BG6B-BNG31Protein G6bTHAMY

Platelet inhibition via ITIM-mediated recruitment of phosphatases (e.g., SHP-1, SHP-2) Inhibition of GPVI:FcRγ and CLEC1B receptor signaling in platelets