Integrin beta 4 (CD104, mRNA: ITG beta 4) contributes to anchoring cells to the extracellular matrix and is regulated in many cancer types where it contributes to tumor progression. One splice variant, integrin beta 4E, is poorly characterized. We extracted several mutations from tumor samples within ITGB4 near the splice site that controls ITG beta 4E production, and computational analysis predicted six of these would alter splicing to alter ITG beta 4E abundance. One of these mutations, from an esophageal squamous cell carcinoma sample, was predicted to increase splicing toward ITG beta 4E. We verified this effect using a minigene, and observed that integrin beta 4E slows esophageal squamous cell migration while other variants enhance migration, demonstrating that integrin beta 4E regulation through mutations may contribute to esophageal squamous cell tumorigenesis. (C) 2020 Published by Elsevier Inc.