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The current evidence assessing the association between PPY (HGNC:9327) and morbid obesity (MONDO_0005139) is limited and somewhat conflicting. In one multi‐patient study evaluating the leptin–melanocortin pathway (PMID:39419959), 54 patients (22 carriers PMID:39419959) were assessed for weight loss outcomes after endoscopic transoral outlet reduction. Although PPY was included among the 21 genes analyzed, the study did not provide PPY‐specific segregation data or robust variant effect estimates to support its independent role in morbid obesity.
In contrast, a candidate gene study focused on variants in related genes (PMID:17235527) reported no significant association for PPY variants with severe obesity, even while identifying significant signals for other genes in the pathway. Moreover, no direct functional or experimental studies have been reported that specifically evaluate the impact of PPY alterations on obesity phenotypes. Together, these data render the gene–disease association as disputed, thereby limiting its current clinical utility for diagnostic decision‑making and precision therapeutic development.
Gene–Disease AssociationDisputedOne study evaluating the leptin–melanocortin pathway did not provide gene-specific PPY segregation data (PMID:39419959), and a subsequent candidate gene analysis reported no significant association for PPY variants (PMID:17235527). Genetic EvidenceLimitedThe available genetic evidence lacks robust PPY-specific variant data and fails to establish a statistically significant link between PPY and morbid obesity. Functional EvidenceLimitedNo direct functional studies have been performed to assess the pathogenic impact of PPY variants in morbid obesity, despite the gene's inclusion in pathway analyses. |