H4C16 encodes a core histone protein that is a fundamental component of nucleosomes, which wrap and compact DNA into chr12. Based on limited published evidence, H4C16 plays a central role in regulating DNA accessibility and is involved in transcription regulation, DNA repair, DNA replication, and chr12 stability through histone post-translational modifications and nucleosome remodeling. H4C16 is associated with Tessadori-Bicknell-Van Haaften neurodevelopmental syndromes 1-4, indicating its importance in human development 1.