RNF186 – Ulcerative Colitis

RNF186 has emerged as a critical gene in the pathogenesis of ulcerative colitis, with studies demonstrating that both protective and risk‐conferring variants contribute to disease susceptibility. Large-scale case‑control analyses have revealed that a protein‑truncating variant, c.535C>T (p.Arg179Ter), is associated with a significantly lower odds ratio (OR = 0.30) in ulcerative colitis patients compared to controls (PMID:27503255). This finding was identified in a robust dataset comprising 11,148 ulcerative colitis patients and nearly 300,000 controls, underscoring the variant’s potential clinical relevance.

Further genetic evidence is provided by independent replication studies in diverse populations where additional rare non‑synonymous RNF186 variants were observed to influence disease risk with moderate effect sizes (PMID:24068945; PMID:21304977). Although no conventional familial segregation data were reported, the consistency across multi‑patient studies supports a strong association between RNF186 variants and ulcerative colitis.

Functional studies have also delineated a plausible mechanism of pathogenicity. The truncating mutation leads to reduced expression levels and altered subcellular localization of RNF186, suggesting a loss‑of‑function effect that is concordant with the protective phenotype observed in patients (PMID:27503255). These experimental findings provide an important link between the genetic variant and its biological consequences, reinforcing its clinical impact.

In summary, the convergent evidence from large cohort studies, replication across ethnic groups, and supporting functional assays demonstrates a strong gene‑disease association between RNF186 and ulcerative colitis. This association reflects the complexity of disease inheritance, with both protective and risk‐conferring variants contributing to the overall genetic architecture.

The integration of genetic and experimental evidence emphasizes the clinical utility of assessing RNF186 variation in ulcerative colitis. This insight offers potential for improving diagnostic decision‑making and guiding therapeutic strategies, with further validation studies likely to expand its translational application.

Key Take‑home: RNF186 serves as a robust genetic marker for ulcerative colitis, providing actionable insights for diagnostics and future therapeutic research.

References

• Nature Communications • 2016 • A protein‑truncating R179X variant in RNF186 confers protection against ulcerative colitis PMID:27503255
• PloS One • 2011 • An investigation of genome‑wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians PMID:21304977
• PLoS Genetics • 2013 • Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis PMID:24068945

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