Exome sequencing studies have identified multiple genes harboring de novo 
loss-of-function (LoF) variants in individuals with autism spectrum disorders 
(ASD), including TBR1, a master regulator of cortical development. We performed 
ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound 
regions are enriched adjacent to ASD genes. ASD genes were also enriched among 
genes that are differentially expressed in Tbr1 knockouts, which together with 
the ChIP-seq data, suggests direct transcriptional regulation. Of the nine ASD 
genes examined, seven were misexpressed in the cortices of Tbr1 knockout mice, 
including six with increased expression in the deep cortical layers. ASD genes 
with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of 
LoF mutations in a reference human population and among Icelanders. We then 
leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. 
Our findings highlight a TBR1-regulated network of ASD genes in the developing 
neocortex that are relatively intolerant to LoF mutations, indicating that these 
genes may play critical roles in normal cortical development.