摘要：SummaryTENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms ofTENM4in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in theTENM4gene through target sequencing ofTENM4in 68 SCZ families. We further demonstrated that aberrant expression ofTen-mleads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression ofTen-mwas related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence thatTENM4contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.Graphical abstractDisplay OmittedHighlights•Possible pathogenic rare missense mutations inTENM4gene contribute to SCZ•Aberrant expression ofTen-mleads to behavioral disturbances related to SCZ symptoms•Ten-maffects stimulation, metabolic process, neurogenesis, and ATPase activityGenetics; Human genetics; Human Genetics; Molecular genetics; Neurogenetics; Psychology
