HELLS and immunodeficiency disease: For example, for the H2A variants, mutations of LSH/HELLS gene, a chromatin remodeler known to interact with MacroH2A, causes Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome, characterized by immunodeficiency, neurologic defects, and reduced growth (Xu et al., 2021).