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Recent large‑scale case‑control studies have implicated PPP1R14A (HGNC:14871) in prostate cancer (MONDO_0008315) risk. In a Nature Communications study, imputed prostate tissue gene expression was analyzed in 233,955 European ancestry individuals (14,616 cases, [PMID:31308362]), revealing a statistically significant association for PPP1R14A. A subsequent Norwegian study further supported this association in a cohort of 779 patients ([PMID:29181843]). These independent investigations, conducted in multi‑ethnic populations including a trans‑ethnic meta‑analysis of 9,117 subjects, provide a robust genetic backing for the role of PPP1R14A in prostate cancer predisposition.
Although specific causative coding variants in PPP1R14A have not been reported (no valid HGVS string is available from the supplied evidence), the association signals arise from well‐powered analyses using transcriptome‑wide methods. The genetic evidence is bolstered by rigorous statistical analyses and replication across distinct cohorts, underscoring its clinical relevance.
Functional data, while not directly from prostate cancer models, indicate that PPP1R14A plays a role in smooth muscle regulation via myosin phosphatase pathways. This is supported by studies of tissue‑specific expression and alternative splicing in smooth muscle (relevant to prostate physiology), lending biological plausibility to the genetic association. However, direct functional assays in prostate tissue remain limited, warranting further investigation.
No significant conflicting evidence has been presented, and the available data converge to support a strong association between PPP1R14A and prostate cancer risk. The combined genetic and functional findings suggest that PPP1R14A could serve as a valuable marker in risk assessment frameworks.
Key take‑home: PPP1R14A is a promising candidate for integration into prostate cancer risk prediction tools, with robust multi‑ethnic genetic support and emerging functional insights reinforcing its clinical utility.
Gene–Disease AssociationStrongAssociation supported by large‑scale investigations including 14,616 cases ([PMID:31308362]) and replication in a Norwegian cohort of 779 patients ([PMID:29181843]). Genetic EvidenceStrongRobust association signals observed in multi‑ethnic cohorts and a trans‑ethnic meta‑analysis (N = 9,117, [PMID:31308362]) underpin the genetic contribution of PPP1R14A. Functional EvidenceLimitedFunctional studies in smooth muscle contexts provide biological plausibility, despite the absence of direct prostate cancer models. |