TNXB and cholesteatoma: Fig 2A illustrates the results of our functional profiling of gene lists carried out as part of the overlap analysis between families—common terms that were statistically enriched included GTPase regulator activity, calcium ion binding, and degradation of the ECM. ECM proteins, COCH and TNXB, were consistently down-regulated in cholesteatoma samples across several transcriptomic [14, 15, 45] and proteomic studies [46, 47]. In addition, several S100 genes known to regulate calcium binding and regulate ion channels show dysregulated expression patterns in cholesteatoma [14, 15, 45].