Integrative Multi-Omics Characterization and Structural Insights into the Poorly Annotated Integrin

backgroundAccurate annotation of gene isoforms remains one of the major obstacles in translating genomic data into meaningful biological insight. Laminin-binding integrins, particularly integrin α6 (

methodsWe combined comparative genomics across primates with targeted re-alignment to assess exon conservation and annotation fidelity; analyzed RNA-seq for exon-level usage; applied splice-site prediction to evaluate inclusion potential; surveyed cancer mutation resources for exon-specific variants; and used structural/disorder modeling to infer effects on the β-propeller.

resultsExon X2 is conserved at the genomic level but inconsistently annotated, reflecting the limitations of current annotation pipelines rather than genuine evolutionary loss. RNA-seq analyses reveal low but detectable expression of X2, consistent with weak splice site predictions that suggest strict regulatory control and condition-specific expression. Despite its rarity, recurrent mutations in exon X2 are reported in cancer datasets, implying possible roles in disease. Structural modeling further indicates that X2 contributes to a flexible, disordered region within the β-propeller domain, potentially influencing laminin binding or β-subunit dimerization.

conclusionsAltogether, our results suggest that