Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
In two independent genome‑wide association studies of pediatric‑onset inflammatory bowel disease, association signals near PSMG1 have been observed, suggesting that variation in or near this gene may confer increased risk for inflammatory bowel disease (PMID:18758464, PMID:19786746). The first study, which evaluated 1,011 cases against 4,250 controls, identified novel loci on chromosomes 20q13 and 21q22, with the latter locus mapping in proximity to PSMG1. The second study replicated the association in an independent pediatric cohort, further supporting a role for PSMG1 in the disease. Although the studies included a substantial number of patients, no familial segregation data or detailed variant‑level information was available to provide additional confirmation. Inherited susceptibility in inflammatory bowel disease is complex and likely influenced by multiple loci, as highlighted by the lack of a clear Mendelian inheritance pattern. Overall, the genetic evidence suggests a modest but reproducible association between PSMG1 and inflammatory bowel disease.
Despite the evidence from multi‑patient studies, functional studies that would elucidate the mechanism of pathogenicity for PSMG1 in inflammatory bowel disease are lacking. The absence of functional assessment precludes assigning a higher ClinGen evidence tier at this time. Consequently, the overall gene‑disease association is currently classified as Limited, emphasizing the need for further investigation including detailed variant analyses and functional characterization. Key take‑home: while the observed GWAS associations support a role for PSMG1 in inflammatory bowel disease, additional studies are essential to translate these findings into robust diagnostic and therapeutic strategies.
Gene–Disease AssociationLimitedAssociation supported by two independent GWAS studies in pediatric‑onset IBD cohorts (1,011 cases (PMID:18758464) and replication (PMID:19786746)). Lack of familial segregation and detailed variant‑level data limits stronger assertions. Genetic EvidenceLimitedGWAS signals near PSMG1 have been observed in two separate studies; however, the absence of discrete coding variants and a comprehensive variant spectrum precludes assignment of a higher tier. Functional EvidenceLimitedNo functional or mechanistic studies have been reported to support the role of PSMG1 in IBD pathogenesis. |