ACVR2A

ACVR2A encodes activin receptor type 2A, a TGF-β family type II receptor that binds activin and participates in receptor complexes driving Smad2/3 signaling^[1]. Mechanistically, Activin A uses ACVR1B as the type I receptor with ACVR2A or ACVR2B as type II receptors, distinguishing ACVR2A from type I receptors that define downstream pathway output^[2]. In gastrointestinal cancer models, ACVR2 coding microsatellites undergo frameshift mutation in mismatch repair-deficient cells, which abrogates TGF-β family receptor signaling^[3]. In MSI-high colon cancer, ACVR2 mutation occurred in 83% of tumors and frequently caused loss of ACVR2 protein expression^[4]. In colorectal cancer with microsatellite instability, ACVR2 frameshift mutation was reported in 92% of tumors, supporting its use as a molecular feature for MSI-focused tumor biology studies^[5]. Compared with related pathway receptors, ACVR2A should therefore be studied with attention to ACVR2B and ACVR1B co-receptor context, ligand-dependent Smad2/3 readouts, and mutation-driven loss-of-function models^[2][3][4].