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We generated human excitatory neurons using a protocol for rapid 21-day induction using neurogenin-2 overexpression (Zhang et al., 2013) in a publicly available control iPSC line. We validated the glutamatergic neuronal identity of the neurons by immunofluorescence and transcriptomics. We exposed 6 of the 12 replicate neuron cultures to therapeutic plasma levels of clozapine (300 ng/mL) for the last 3 days of culture, and the remaining 6 to replicates to the clozapine solvent alone (methanol) to be used as controls. We harvested the cultures and extracted total RNA, depleted ribosomal RNA and subjected them to RNA sequencing. Of the 6 control replicates 2 failed RNA quality control, and thus a total of 6 exposed and 4 control cultures were used for further analysis. Here, we provide that raw sequencing data as well as a list of all of the genes and their expression levels resulting from the RNA-sequencing. This dataset can be used as a reference data for future studies that access additional neuronal cell types, clozapine exposure conditions, and other antipsychotic medication.Related Research Article: Das, D., Peng, X., Lam, A.N., Bader, J.S., Avramopoulos, D., 2021. Transcriptome analysis of human induced excitatory neurons supports a strong effect of clozapine on cholesterol biosynthesis. Schizophr Res 228, 324–326. (Das et al., 2021).