KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it is also a known cancer driver gene, with multiple somatic mutations found in a few cancer types. In this study, we looked at eleven missense variants in lung squamous cell carcinoma, one of the most common lung cancer subtypes, to see how they affect the KDM6A catalytic mechanisms. We found that they influence the interaction with histone H3 and the exposure of the trimethylated Lys27, which is critical for wild-type physiological function to varying degrees, by altering the conformational transition.
Keywords: DCCM, dynamic cross-correlation map; Epigenetics; GaMD, gaussian accelerated molecular dynamics; IDR, intrinsically disordered region; LUSC, lung squamous cell carcinoma; MD, molecular dynamics; Molecular Dynamics simulation; PCA, principal component analysis; PMF, potential of mean force; Pathogenicity estimation; RMSD, root mean squared deviation.
© 2022 The Author(s).