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UBA7 and Ulcerative Colitis

Recent studies have identified UBA7 (HGNC:12471) as a candidate gene associated with ulcerative colitis (MONDO:0005101). In a comprehensive colon eQTL mapping study, UBA7 was among a set of target genes for inflammatory bowel disease (IBD)‐associated variants in colonic tissue, suggesting a potential regulatory role in this complex disorder (PMID:25766683).

In an independent multi-patient study conducted in a South Asian population, UBA7 was included in a panel of candidate genes evaluated for genetic associations with both ulcerative colitis and Crohn disease. Although significant associations were primarily reported for other loci, the inclusion of UBA7 supports its consideration as a contributing factor to the polygenic risk burden observed in IBD (PMID:30568945).

From the genetic evidence perspective, the studies available have not identified numerous unrelated probands carrying pathogenic alleles in UBA7, nor is there clear familial segregation data. Thus, while the preliminary association signals are consistent with a potential role in disease pathogenesis, the overall evidence for a direct causal link remains modest.

At the functional level, UBA7 encodes an E1-like enzyme that is critical for the ISGylation cascade—a post-translational modification system involved in immune regulation. Several functional studies have highlighted the importance of ISGylation in modulating antiviral responses and immune signaling (PMID:18560560, PMID:19073728, PMID:25406959). Although these assays were performed in contexts distinct from ulcerative colitis, they provide biological plausibility that dysregulation of UBA7 function could influence inflammatory processes in the colon.

Integration of the genetic and experimental data suggests that while UBA7’s contribution to ulcerative colitis pathogenesis is supported by tissue-specific regulatory signals and a relevant mechanistic pathway, the association remains preliminary with limited direct variant and segregation evidence. Additional large-scale, family-based studies and functional experiments specific to colonic inflammation are needed to strengthen this connection further.

Key take‑home: UBA7 represents a promising but currently limited genetic contributor to ulcerative colitis, meriting further investigation to clarify its diagnostic and therapeutic potential in IBD.

References

  • BMC Genomics • 2015 • Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci PMID:25766683
  • World journal of clinical cases • 2018 • Genetic associations of inflammatory bowel disease in a South Asian population PMID:30568945
  • PloS one • 2008 • HyperISGylation of Old World monkey ISG15 in human cells PMID:18560560
  • Journal of virology • 2009 • ISG15 Arg151 and the ISG15-conjugating enzyme UbE1L are important for innate immune control of Sindbis virus PMID:19073728
  • Journal of interferon & cytokine research • 2015 • Murine Herc6 Plays a Critical Role in Protein ISGylation In Vivo and Has an ISGylation-Independent Function in Seminal Vesicles PMID:25406959

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

UBA7 has been identified as a candidate gene through colon eQTL mapping and inclusion in a multi-patient association study for IBD, but lacks extensive proband and segregation data (PMID:25766683, PMID:30568945).

Genetic Evidence

Limited

While UBA7 appears in the context of IBD-associated eQTLs and genetic panels, specific variant-level data and segregation analysis remain minimal.

Functional Evidence

Moderate

Functional assays demonstrate that UBA7 plays a crucial role in the ISGylation process, an immune regulatory pathway, lending biological plausibility to its potential role in ulcerative colitis, though direct disease-specific functional data are limited (PMID:18560560, PMID:19073728, PMID:25406959).