Resequencing analysis of Zic2 in Japanese patients with schizophrenia revealed three novel nonsynonymous mutations in ZIC2. Functional analysis of these mutations in the Zic2kd/+ mouse model of schizophrenia indicated that the R409P mutation results in severe loss-of-function. We showed that the transcriptional activation capacity of the Zic2-R409P protein was about 20% that of the wild-type protein; which corresponds to the decreased protein production from the Zic2kd allele shown previously8. This finding in turn validates Zic2kd/+ mice as an animal model of the R409P mutation in schizophrenia. The patient with the R409P mutation was diagnosed with residual-type schizophrenia.