Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission (PubMed:30455454, PubMed:31515109). May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics (PubMed:31515109). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (PubMed:22939622). The relevance of histone methyltransferase activity is however subject to discussion (PubMed:27864380, PubMed:30455454). L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-homocysteine Interacts with components of the PAF1 complex (PAF1C) such as LEO1, CTR9 and CDC73 (PubMed:27864380). Interacts with NCOR1 (PubMed:27864380). Interacts with HDAC3 (PubMed:30455454). Localizes to active transcribed genes. Ubiquitously expressed. Mid-gestation lethality due to severe developmental delay such as vascular abnormalities in the embryo and placenta, reduced cellular proliferation and increased apoptosis (PubMed:27864380). Defects are probably due to a widespread impairment in the regulation of gene expression (PubMed:27864380). Setd5-haploinsufficient mice display altered neuronal network connectivity leading to autistic-like behaviors (PubMed:30655503, PubMed:30455454, PubMed:31515109). Haploinsufficient Setd5 cortical neurons show reduced synaptic density and neuritic outgrowtho, with corresponding decreases in network activity and synchrony by electrophysiology (PubMed:30655503). Haploinsufficient mice display several autism-like behaviors, including hyperactivity, cognitive deficit, and altered social interactions (PubMed:30455454, PubMed:31515109, PubMed:30655503). According to a report, lacks histone methyltransferase activity and regulates chromatin by interacting with HDAC3 and PAF1 complex (PAF1C) complex (PubMed:30455454). According to another publication, displays histone methyltransferase activity and directly trimethylates 'Lys-36' of histone H3 (H3K36me3) (PubMed:31515109).