Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+) + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-homocysteine Interacts with the ligand-binding domains of RARA and THRA in the absence of ligand; in the presence of ligand the interaction is severely disrupted but some binding still occurs. Interacts with the ligand-binding domains of RXRA and ESRRA only in the presence of ligand. Interacts with ZNF496 (By similarity). Interacts with AR DNA- and ligand-binding domains. Expressed in the fetal/adult brain, kidney, skeletal muscle, spleen, and the thymus, and faintly in the lung. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98. A chromosomal aberration involving NSD1 is found in an adult form of myelodysplastic syndrome (MDS). Insertion of NUP98 into NSD1 generates a NUP98-NSD1 fusion product. Belongs to the class V-like SAM-binding methyltransferase superfamily.