Specifically, the missense mutation involves a single nucleotide change of a valine to a leucine within the transmembrane domain of Type 3 Neuregulin 1. It is thought that this single nucleotide change affects the ability of γ-secretase to cleave the intracellular domain (ICD) of the Type 3 isoform of Neureglin 1. That is, the valine to leucine mutation within the transmembrane domain of Type 3 Neuregulin 1 decreases the amount of ICD that γ-secretase is able to cleave. The ICD of Type 3 Neuregulin 1 has been shown to suppress transcription of inflammatory cytokines, including IL-1β, IL-6, IL-10, IL-8, IL12-p70, and TNF-α. Using recombinant ErbB4 to stimulate the cleavage of the intracellular domain of Type 3 Neuregulin 1, a receptor for Type 3 Neuregulin 1, Marballi et al. showed that increased levels of the ICD lead to a decrease in IL-6 levels. Given the involvement of Neuregulin 1 in schizophrenia and the finding that the valine to leucine missense mutation in mice produces working memory deficits, NRG1 seems a likely genetic candidate that confers susceptibility to the development of schizophrenia.