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A recent study has implicated ZNF460 in the pathogenesis of schizophrenia through comprehensive genomic and functional investigations. In a nuclear family affected by schizophrenia, whole‑exome sequencing identified a series of rare variants that co‑segregated with the disorder, drawing attention to the potential role of ZNF460 in disease development (PMID:37763159).
Genetic evidence specifically highlighted a missense variant, c.691A>G (p.Lys231Glu), in ZNF460. This variant was observed in the context of a broader mutational profile where six rare variants were identified, with the ZNF460 variant clearly co‑segregating with schizophrenia in the affected family (PMID:37763159).
Segregation analysis within this nuclear family revealed that in addition to the proband, at least two additional affected relatives carried the ZNF460 variant. The observed autosomal dominant transmission pattern supports its contributory role in disease predisposition (PMID:37763159).
Functional assessments further corroborated the genetic findings. The study reported experimental data that demonstrated disruption in chromatin modulation and aberrant extracellular matrix–receptor interaction pathways in cellular models, findings that are consistent with the neural pathophysiology of schizophrenia (PMID:37763159).
Integration of the genetic and functional data suggests that while the current evidence is derived from a single nuclear family, the convergence of segregation, bioinformatic enrichment, and experimental data provides a moderately strong case for the association between ZNF460 and schizophrenia. Although further studies in independent cohorts are warranted, the existing data already offer valuable mechanistic insight into disease biology.
Key take‑home: The association between the ZNF460 c.691A>G (p.Lys231Glu) variant and schizophrenia presents a promising avenue for improved diagnostic decision‑making and highlights a potential target for future therapeutic interventions.
Gene–Disease AssociationModerateA nuclear family study showed that the ZNF460 c.691A>G (p.Lys231Glu) variant segregated with schizophrenia, with supportive bioinformatic analyses and functional data implicating disrupted chromatin modulation (PMID:37763159). Genetic EvidenceModerateGenetic data from the family identifies a clear missense variant in ZNF460 that co-segregates with schizophrenia, supporting its contributory role despite being limited to a single family study (PMID:37763159). Functional EvidenceModerateFunctional assessments demonstrated aberrations in chromatin modulation and ECM-receptor interactions consistent with schizophrenia pathology, providing mechanistic support for ZNF460 involvement (PMID:37763159). |