The deduced 1,437 amino acid NSD3 protein contains two PWWP domains involved in protein-protein interactions, five PHD-type zinc finger motifs found in chromatin-associated proteins, a SAC (SET-associated cys-rich) domain, a SET domain and a C-terminal C5HCH domain. Two NSD3 variants have been identified. The short variant comprised of 645 amino acids, arises from alternative polyadenylation and exon splicing and contains a single PWWP domain. A longer NSD3 variant, which is only expressed in HeLa cells, is comprised of 1,388 amino acid residues. The human WHSC1L1 gene, which encodes the NSD3 protein, shares 68% and 55% identity with mouse Nsd1 and human WHSC1, respectively. Highest expression of NSD3 is observed in brain, heart and skeletal muscle tissues; lower levels of NSD3 expression are observed in the liver and lungs.