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The association between N4BP1 (HGNC:29850) and schizophrenia (MONDO_0005090) is currently supported by limited genetic evidence. A rare missense variant, c.19C>G (p.Leu7Val), was identified in a single nuclear family with schizophrenia, where it segregated with the disorder in affected individuals (PMID:37763159). This variant was reported in the context of a panel of six rare variants from the same study, but for N4BP1 the evidence is confined to this nuclear family, resulting in a modest case series contribution.
Functional studies provide additional insight by demonstrating that N4BP1 negatively regulates NF-κB signaling via its interaction with key modulators, an effect shown in vitro and supported by murine models (PMID:33654074). These experimental findings offer a plausible mechanistic link between dysregulated inflammatory signaling and the pathogenesis of schizophrenia. However, while the functional evidence is moderately supportive, the overall genetic evidence remains limited. Key take‑home sentence: In its current state, the integration of rare variant segregation and supportive functional data suggests that N4BP1 may contribute to schizophrenia risk, but further studies are needed to firmly establish its clinical utility.
Gene–Disease AssociationLimitedGenetic association limited to a single nuclear family with modest segregation of the c.19C>G (p.Leu7Val) variant (PMID:37763159). Genetic EvidenceLimitedEvidence is derived from a single family-based case report, where the identified variant segregated with disease in a limited number of affected relatives (PMID:37763159). Functional EvidenceModerateExperimental studies show that N4BP1 modulates NF-κB signaling, providing mechanistic support that may relate to neuroinflammatory processes implicated in schizophrenia (PMID:33654074). |