ASXL2 is a human homolog of the Drosophila asx gene. Drosophila asx is an enhancer of trithorax and polycomb (ETP) gene that encodes a chromatin protein with dual functions in transcriptional activation and silencing.

The deduced 1,435-amino acid protein shares 29.8% identity with ASXL1. ASXL1 and ASXL2 share significant homology in their N-terminal and middle domains, which the authors designated the ASXN and ASXM domains, respectively, and both proteins have a C-terminal plant homeodomain (PHD). Katoh and Katoh (2003) also identified a putative splice variant of mouse Asxl2, which encodes a protein with an in-frame internal deletion of about 50 amino acids compared with full-length human ASXL2