Histone methyltransferase that specifically represses expression of the surface antigen-coding var genes by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3) on var genes. SETVS-dependent H3K36me3 is specifically involved in var genes silencing, a central step malaria pathogenesis: each parasite contains 60 distinct var genes that each code for a different PfEMP1 protein. During infection, the clonal parasite population expresses only 1 gene at a time, while the 59 other var genes are silenced. The parasite then switches to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. Represses expression of both var mRNA and antisense long non-coding RNA. 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 Localizes along the entire gene body of silent var genes, including the transcription start site of var genes and the respective intronic antisense promoter. Highly expressed in early trophozoite stages. Expression is then reduced in late trophozoites and elevated again in schizonts. Leads to expression of all var genes in the ring stage. Parasites lacking SETVS could be used as an antimalarial vaccine because of its ability to express all PfEMP1 proteins, to which the antibody would provide efficient protective immunity against malaria. Belongs to the class V-like SAM-binding methyltransferase superfamily.