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Rare, de novo truncating mutations in KIF17 have been reported in a single sporadic schizophrenia (SCZ) patient, supporting a limited but biologically plausible role for KIF17 disruption in disease etiology. In a cohort of 188 individuals with SCZ, one patient carried a de novo nonsense variant in KIF17, and no such mutations were observed in additional SCZ (n = 142), intellectual disability (n = 95), or control (n = 568) subjects (PMID:20646681). Functional knockdown of the orthologous transcript in developing zebrafish embryos produced neurodevelopmental defects, consistent with a loss-of-function mechanism and perturbation of glutamatergic synapse formation (PMID:20646681). Prior biochemical studies of the C. elegans kinesin OSM-3 have defined an autoinhibitory hinge mechanism regulating motor processivity, underscoring the importance of proper KIF17 regulation in vertebrate neuronal development (PMID:17000874). No segregation data are available, and no additional unrelated probands have been described.
Gene–Disease AssociationLimitedSingle de novo truncating variant identified in one SCZ proband with functional zebrafish validation Genetic EvidenceLimitedOne proband with a de novo nonsense KIF17 variant in a cohort of 188 SCZ cases ([PMID:20646681]) Functional EvidenceModerateZebrafish knockdown of KIF17 ortholog produces neurodevelopmental defects; autoinhibition mechanism supported by C. elegans studies |