USP2 and Intellectual Disability

USP2 has emerged as a candidate gene for intellectual disability (MONDO_0001071) based on multi‐patient exome sequencing studies. Variants in USP2 were identified among a broader panel of genes in a large intellectual disability cohort (PMID:27431290), yet the recurrence and segregation of USP2‐specific variants have not been extensively documented. Consequently, the available genetic evidence remains limited, with only a few probands identified and inadequate family segregation data to firmly establish causality.

Functional studies, however, provide moderate support for a biological role of USP2 in neurodevelopment. Multiple investigations have demonstrated that alternative splicing of USP2 results in distinct isoforms with roles in cell cycle progression and apoptosis, thereby offering a plausible mechanistic link to neurodevelopmental dysfunction (PMID:29230097, PMID:28536428, PMID:27436899). Key Take‑home: While additional genetic studies are required to robustly confirm the association, the integration of preliminary genetic signals with supportive functional data highlights USP2 as a promising candidate for further investigation in the context of intellectual disability.

References

• Molecular psychiatry • 2017 • Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield PMID:27431290
• International journal of biological sciences • 2017 • The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products PMID:29230097
• Scientific reports • 2017 • The molecular determinants for distinguishing between ubiquitin and NEDD8 by USP2 PMID:28536428
• Proceedings of the National Academy of Sciences of the United States of America • 2016 • Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21 PMID:27436899

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