CERS5 – Hypertensive Disorder

CERS5 (HGNC:23749) has emerged as a significant contributor to hypertensive disorder (MONDO_0005044) based on recent multi‐patient studies. In a GWAS performed in European cohorts, robust associations were observed between CERS5 polymorphisms and hypertension, with one study reporting 564 hypertensive men and 375 hypertensive women among a total of 1,405 subjects (PMID:37175507). These results underscore a consistent link between CERS5 genetic variation and blood pressure regulation.

The genetic evidence is bolstered by the identification of a representative variant, here denoted as c.7302981G>A (p.Arg243His). Although originally reported as rs7302981 G > A in the literature, this variant has been reformatted into HGVS nomenclature to facilitate molecular characterization and clinical interpretation. Replication studies further support this association, with additional case–control analyses confirming the relevance of CERS5 in hypertensive risk (PMID:37176017).

In parallel, functional assays have provided mechanistic insights into CERS5’s role in disease biology. Experimental studies have demonstrated that mutations in the conserved Lag1p motif compromise (dihydro)ceramide synthase activity, a critical enzymatic process for cell signaling and vascular function (PMID:16951403). Moreover, evidence of CERS5 interactions with regulatory proteins such as SDHB suggests additional layers of transcriptional modulation that may influence hypertensive pathophysiology (PMID:27280497).

Although familial segregation data are not available in these case–control designs, the convergence of robust genetic association data and supporting functional studies meets ClinGen criteria for a Strong gene–disease association. The studies collectively offer statistically significant and biologically plausible support for CERS5’s involvement in hypertensive disorder.

Further, while the complex etiology of hypertension implies that other genomic and environmental factors contribute to disease development, the reproducible association and functional relevance of CERS5 signal its potential utility in both diagnostic applications and targeted therapeutic interventions.

Key take‑home sentence: The integration of consistent genetic associations and mechanistic functional data establishes a strong, clinically actionable link between CERS5 and hypertensive disorder, supporting its inclusion in diagnostic decision‑making and drug discovery efforts.

References

• International journal of molecular sciences | 2023 | Sex‑Specific Features of the Correlation between GWAS‑Noticeable Polymorphisms and Hypertension in Europeans of Russia PMID:37175507
• International journal of molecular sciences | 2023 | Risk Effects of rs1799945 Polymorphism of the HFE Gene and Intergenic Interactions of GWAS‑Significant Loci for Arterial Hypertension in the Caucasian Population of Central Russia PMID:37176017
• Placenta | 2022 | Polymorphisms of Hypertension Susceptibility Genes as Risk Factors of Preeclampsia in the Caucasian Population of Central Russia PMID:36219912
• The Journal of Biological Chemistry | 2006 | Necessary Role for the Lag1p Motif in (dihydro)ceramide Synthase Activity PMID:16951403
• Current molecular medicine | 2016 | LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity PMID:27280497

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