Histone-lysine N-methyltransferase NSD3 is an enzyme that in humans is encoded by the WHSC1L1 gene.

This gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. The function of the protein has not been determined. Two alternatively spliced variants have been described. [provided by RefSeq]. Transcript variant: This variant (long) contains an alternative 3' end sequence. The longer protein encoded has a different carboxy terminus than the protein encoded by variant short.
Function: Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.