Ion channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) channels consist of two members (KCNB1 and KCNB2) that encode for Kv2.1 and Kv2.2 channels, respectively. These channels are major contributors of delayed rectified potassium currents arising from neuronal soma that modulate overall excitability of neurons. In this study, we identified several point mutations in the KCNB2 gene, expressed in an autosomal-dominant fashion, in patients suffering from a range of neuropsychiatric disorders that include Zimmerman-Laband syndrome, global developmental delay, delayed motor milestones and attention deficit hyperactivity disorder. We characterized these variants by expressing them in oocytes of Xenopus laevis and conducting cut-open voltage clamp electrophysiology to study channel properties. Our initial datasets indicate no significant change in absolute conductance and conductance-voltage relationships of disease variants as compared to wild type (WT), when expressed either alone or co-expressed with WT-Kv2.2. These variants, however, show increased inactivation that is shifted to hyperpolarized potentials. We suggest that these effects of the mutations on Kv2.2 channel inactivation may contribute to hyper-excitability of neurons that express these variants, which leads to disease onset.