The 24-year-old played 72 minutes of Italy's 2-2 draw with Bulgaria on Saturday but sustained a shoulder problem that has now forced him out of Antonio Conte's squad.
"Italy midfielder Bertolacci is ruled out from Italy-England match due to injury, the player will return today to Genoa," the FIGC confirmed on Twitter.
Bertolacci made his debut for the national side in November, having maintained his fine form for Genoa this term.
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