SEC61B and Autosomal Dominant Polycystic Liver Disease

SEC61B has emerged as a candidate gene in the setting of autosomal dominant polycystic liver disease, as evidenced by multiple multi‐patient studies and population sequencing analyses. These studies indicate that mutations affecting SEC61B contribute to the disease phenotype by disrupting normal hepatic cystogenesis, largely through a reduction in functional polycystin‑1 (PMID:30652979).

The genetic evidence is supported by independent reviews that aggregate data from case reports and large sequencing cohorts. Although precise variant details are not abundantly reported, the overall contribution of SEC61B variants is underscored by their presence in up to approximately 50% of patients with isolated polycystic liver disease (PMID:30652979; PMID:30135240). This consistency across different studies reinforces the robustness of the genetic association.

Inheritance follows an autosomal dominant pattern, and while specific familial segregation details remain incompletely quantified in the published literature, the accumulation of genetic findings from unrelated individuals provides a strong basis for disease causality. The population sequencing study further detailed that loss‐of‑function mutations in ADPLD genes, including SEC61B, occur at a frequency consistent with a pathogenic role (PMID:30135240).

Functional studies have provided additional support by demonstrating that SEC61B dysfunction leads to a decrease in polycystin‑1 levels—an essential protein for maintaining normal biliary architecture. In vitro models have shown that impaired SEC61B activity results in disrupted protein processing, which mirrors the cellular defects observed in polycystic liver disease (PMID:35571028).

No significant conflicting evidence has been reported that refutes this association, although additional studies to further define segregation patterns and variant-specific impacts would enhance understanding of SEC61B’s role. Overall, the convergence of genetic and functional data provides a clear mechanistic link and supports SEC61B as a key contributor to the pathogenesis of autosomal dominant polycystic liver disease.

Key take‑home: The integration of multi‑patient genetic studies and supportive functional assays confirms that SEC61B plays a crucial role in the development of autosomal dominant polycystic liver disease, offering valuable insights for diagnostic refinement and potential therapeutic targeting.

References

• Current Opinion in Gastroenterology • 2019 • Genetics of polycystic liver diseases PMID:30652979
• Frontiers in Genetics • 2022 • Molecular Mechanisms of Isolated Polycystic Liver Diseases PMID:35571028
• Journal of the American Society of Nephrology : JASN • 2018 • Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing PMID:30135240

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