LRRFIP1 – Schizophrenia

Leucine-rich repeat in Flightless-1 interaction protein 1 (LRRFIP1) has been implicated in schizophrenia (Schizophrenia) through genome-wide association studies. A systematic review of 22 independent GWAS identified common variant signals at the LRRFIP1 locus reaching genome-wide significance (PMID:31096178). No rare coding variants or familial segregation analyses have been reported in schizophrenia cases, resulting in limited genetic evidence under ClinGen criteria.

Although LRRFIP1 regulates Wnt/β-catenin and Akt/mTOR pathways in cerebral ischemia and myogenesis models (PMID:24637094, PMID:28322931), no functional studies have directly assessed its role in schizophrenia‐relevant neuronal systems. The pathogenic mechanism linking GWAS‐associated variation at LRRFIP1 to schizophrenia risk remains uncharacterized. Key take‐home: common‐variant association supports a polygenic contribution but absence of rare variant or disease‐model data limits its current clinical utility for diagnostic decision‐making.

References

• Journal of psychiatric research • 2019 • Unravelling the genetic basis of schizophrenia and bipolar disorder with GWAS: A systematic review PMID:31096178
• Neuroscience • 2014 • Characterization of Gcf2/Lrrfip1 in experimental cerebral ischemia and its role as a modulator of Akt, mTOR and β-catenin signaling pathways PMID:24637094
• Biochimica et biophysica acta. Molecular cell research • 2017 • The alternatively spliced LRRFIP1 Isoform-1 is a key regulator of the Wnt/β-catenin transcription pathway PMID:28322931

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