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UBE2N (HGNC:12492) is an essential mediator of K63-linked polyubiquitination in DNA damage response processes. Multiple studies have evaluated the role of UBE2N in breast cancer (MONDO_0007254) by examining methylation patterns and mutation frequencies in candidate gene panels, yet the clinical data remain sparse. While one multi-patient study analyzed the methylation status of several homologous recombination genes in breast cancer specimens and included UBE2N in its panel (PMID:24581343), there was no strong differential methylation pattern observed specifically for UBE2N in relation to tumor subtype or chemosensitivity.
In a separate study focusing on mutation screening in 123 Northern Finnish breast cancer families, UBE2N (also known as UBC13) was evaluated alongside RNF8 and MMS2. This study did not detect aberrations that could be clearly linked to breast cancer susceptibility and reported an absence of significant familial segregation of potentially disruptive variants (PMID:21774837). Consequently, the current clinical genetic evidence for an association between UBE2N variants and breast cancer risk is limited.
Despite the modest clinical findings, a number of functional studies have consistently demonstrated the critical role of UBE2N in modulating key cellular processes. For instance, mechanistic work has shown that UBE2N mediates K63-linked ubiquitination, influencing p53 localization and transcriptional regulation in response to DNA damage (PMID:17000756). These studies provide robust experimental data that support a plausible biological mechanism linking UBE2N dysfunction with tumorigenesis.
Genetic evidence for UBE2N in breast cancer is predominantly limited by the absence of multiple unrelated probands carrying clearly pathogenic variants and by a lack of compelling segregation data. The negative findings in mutation screening studies underscore the need for larger, well-powered cohort analyses. Meanwhile, the functional evidence remains moderately supportive, as UBE2N’s role in DNA repair is well established and suggests potential mechanistic involvement in breast cancer pathogenesis.
Although the mechanistic data indicate that UBE2N could influence breast cancer development, the overall clinical validity of its association is currently classified as Limited. The conflicting results between functional insights and clinical mutation screening highlight an important gap that warrants further investigation in order to clarify UBE2N’s diagnostic utility in breast cancer.
Key take‑home: UBE2N’s established role in DNA repair pathways makes it a biologically plausible candidate in breast carcinogenesis, yet its clinical association remains limited, underscoring the need for additional studies to define its potential as a diagnostic marker.
Gene–Disease AssociationLimitedLimited proband data with negative mutation screening and a lack of segregation evidence in familial studies PMID:21774837 Genetic EvidenceLimitedA mutation screening of 123 families failed to identify pathogenic variants in UBE2N, and no significant familial segregation was observed PMID:21774837 Functional EvidenceModerateMultiple mechanistic studies demonstrate that UBE2N mediates K63‑linked ubiquitination and modulates p53 function and DNA repair, supporting a biological role in tumorigenesis PMID:17000756 |