UBLCP1 and Psoriasis

This summary evaluates the association between UBLCP1 (HGNC:28110) and psoriasis (MONDO_0005083) based on evidence from large-scale genetic studies. Two independent multi‐patient studies have implicated UBLCP1 as a novel susceptibility gene for psoriasis. In a transcriptome-wide association study of 5,175 cases and 447,089 controls (PMID:34409462), UBLCP1 was identified among 16 conditionally independent genes, while a separate analysis using exome data from 32,043 Chinese Han individuals (PMID:31078570) reported InDel associations involving UBLCP1 among other risk genes.

The genetic evidence supporting the relationship is robust. Although exact proband counts are not individually listed for UBLCP1, the studies involved very large cohorts and identified statistically significant associations in gene-level analyses. The multi-tissue approach and replication across independent studies enhance the overall confidence in the genetic association. The evidence meets criteria for a Strong gene-disease association based on ClinGen guidelines, with significance metrics and replication across distinct cohorts.

Given the complex and multifactorial nature of psoriasis, the inheritance mode is best described as complex. No clear Mendelian segregation pattern has been observed; however, the genetic data indicate that inherited common and rare variants in UBLCP1 contribute to disease risk. The lack of detailed segregation data precludes precise counts of affected relatives with segregating variants.

While specific coding variants for UBLCP1 associated with psoriasis were not detailed in the provided studies, the multi-variant approach (including common regulatory and rare InDel variants) supports a robust genetic contribution. Notably, one functional study in a separate context (PMID:38129378) demonstrated that a mutation in UBLCP1 can impact proteasome regulation and activity. However, because that functional evidence relates to autism spectrum disorder, its direct applicability to psoriasis remains limited.

In summary, integration of large-scale transcriptome-wide and exome-based studies provides a compelling argument for a strong association between UBLCP1 and psoriasis. Although the functional data are not psoriasis-specific, the convergent genetic signals from independent cohorts support the clinical relevance of UBLCP1 in risk assessment for psoriasis. The observed associations offer potential utility in diagnostic decision-making and the development of targeted therapeutic strategies.

Key Take‑home sentence: Strong genetic evidence across large cohorts supports UBLCP1 as a credible susceptibility gene for psoriasis, underscoring its potential value in precision medicine for patient risk stratification.

References

• Human Molecular Genetics • 2021 • A transcriptome-wide association study identifies novel susceptibility genes for psoriasis PMID:34409462
• The Journal of Investigative Dermatology • 2019 • Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases PMID:31078570
• Translational Psychiatry • 2023 • A novel autism-associated UBLCP1 mutation impacts proteasome regulation/activity PMID:38129378

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