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Two independent genetic association studies have evaluated the role of PANX2 (HGNC:8600) in schizophrenia (MONDO:0005090). In the first study, four single-nucleotide polymorphisms in PANX2 were analyzed in a cohort of 381 schizophrenic patients and an equal number of matched controls, but the allele, genotype, and haplotype analyses did not yield statistically significant associations (PMID:17427027). A second study using a larger German cohort of 1173 cases (including 338 individuals with periodic catatonia) and 480 controls identified a modest association at the PANX2 locus (notably the rs4838858-TT genotype, p = 0.02, OR 3.1; PMID:26223428). However, both studies report only limited and inconsistent genetic findings without clear segregation evidence or demonstration of pathogenic rare coding changes. The absence of a validated coding variant based on HGVS criteria further underscores the limited genetic data supporting the role of PANX2 in schizophrenia.
Complementary functional studies have provided moderate evidentiary support by elucidating important biological properties of PANX2. Several in vitro experiments have revealed that N-glycosylation regulates PANX2’s cellular localization and its interaction with PANX1, potentially affecting channel activity and neuronal signaling (PMID:29932112). Additional studies in murine skin and other cellular systems have confirmed that glycosylation and protein–protein interactions modulate PANX2 function, although these assays do not directly correlate with schizophrenia pathogenesis (PMID:34985913; PMID:19692571).
Key take‑home sentence: While PANX2 exhibits biologically relevant mechanisms that may influence neural function, the overall clinical utility of PANX2 variants for schizophrenia diagnosis remains limited and warrants further investigation.
Gene–Disease AssociationLimitedTwo independent studies in diverse populations yielded inconsistent and modest statistical associations with schizophrenia, with no clear replication of pathogenic variants (PMID:17427027, PMID:26223428). Genetic EvidenceLimitedThe genetic evidence is based on common SNP association studies without identification of rare or functional coding variants, resulting in overall limited support. Functional EvidenceModerateIn vitro functional assays demonstrate that N-glycosylation modulates PANX2 localization and interaction with PANX1, suggesting a plausible biological mechanism even though a direct link to schizophrenia remains unestablished. |