SNX31 – Schizophrenia

Whole-exome sequencing in a cohort of 22q11.2 deletion carriers identified a heterozygous frameshift variant in SNX31 exclusively in the individual with schizophrenia, implicating SNX31 as a potential modifier of disease penetrance in this high-risk population. Specifically, a c.963del (p.Trp321CysfsTer23) SNX31 variant was found in the affected proband but absent in a psychosis-free deletion carrier, providing initial genetic evidence for association (PMID:24482440). No additional affected relatives were reported to segregate SNX31 variants.

To date, no functional studies have assessed SNX31’s role in neuronal development or synaptic function relevant to schizophrenia, and the single-patient observation lacks segregation or population-level replication. Notably, a distinct SNX31 frameshift mutation has been shown to underlie familial exudative vitreoretinopathy in a mouse model, indicating that SNX31 disruption is pathogenic in ocular tissues but without known psychiatric manifestations (PMID:37053012). Additional case–control studies and mechanistic work in neural systems are required to substantiate SNX31’s contribution to schizophrenia risk.

Key Take-home: Current data support a limited association between SNX31 and schizophrenia, highlighting the need for further genetic replication and functional characterization before clinical application.

References

• The British journal of psychiatry : the journal of mental science • 2014 • 22q11.2 deletion carriers and schizophrenia-associated novel variants PMID:24482440

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