UBE2Q2 – Chronic Kidney Disease

Large-scale genetic studies have robustly implicated UBE2Q2 in chronic kidney disease. Two independent GWAS meta‐analyses, one involving over 67,000 individuals and a replication cohort of nearly 23,000 subjects, consistently demonstrated that variants in UBE2Q2 are significantly associated with decreased renal function and increased CKD risk (PMID:20383146, PMID:21980298). These studies provide strong statistical evidence based on large case series, underscoring the gene’s role in modulating kidney function.

The genetic evidence reflects a complex mode of inheritance, typical of multifactorial conditions like CKD, where common risk alleles contribute modest effects. Although traditional segregation data is limited, the replication of association signals across multiple cohorts supports the clinical validity of UBE2Q2 as a susceptibility gene in CKD.

Despite the absence of detailed familial segregation data, the aggregate genetic findings are compelling. Both studies reported modest effect sizes for individual risk alleles that, when combined, considerably influence the renal function phenotype. No specific high‐penetrance mutation has been isolated, which is consistent with the complex nature of chronic kidney disease.

While a detailed variant spectrum is not explicitly provided in the multi‐patient studies, the robust association at the locus underscores the contribution of noncoding and regulatory changes that may affect UBE2Q2 expression or function. In the absence of a clearly reported coding variant, the gene’s association is primarily inferred from its statistical signal in population studies.

Complementary functional assays further support the role of UBE2Q2. A study demonstrated that UBE2Q2 is capable of ubiquitin thiolester formation, confirming its enzymatic activity as a ubiquitin‐conjugating enzyme (PMID:16760379). Although these assays were performed in tissue contexts unrelated to the kidney, the demonstration of a conserved enzymatic function offers a plausible mechanistic link between altered ubiquitination and renal pathology.

There is no notable conflicting evidence; all available studies are concordant in supporting the association between UBE2Q2 and chronic kidney disease. However, it is recognized that further targeted studies, particularly functional assessments in renal tissue, are needed to fully elucidate the pathogenic mechanism.

In conclusion, the genetic association of UBE2Q2 with chronic kidney disease is reinforced by powerful GWAS data and is supported by functional evidence demonstrating conserved ubiquitin-conjugating activity. This integrated evidence underscores the clinical utility of UBE2Q2 as a potential marker for CKD risk, with significant implications for diagnostic decision-making and future therapeutic development.

References

• Nature genetics • 2010 • New loci associated with kidney function and chronic kidney disease PMID:20383146
• PLoS genetics • 2011 • Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD PMID:21980298
• Biology of reproduction • 2006 • Demonstration of ubiquitin thiolester formation of UBE2Q2 (UBCi), a novel ubiquitin-conjugating enzyme with implantation site-specific expression PMID:16760379

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