The 49ers’ defense took a devastating injury hit Sunday as star linebacker Fred Warner dislocated fractured his right ankle and will miss the remainder of the season, head coach Kyle Shanahan told reporters after their loss to the Buccaneers.

Warner, a four-time Pro Bowler and already up to 51 combined tackles, was stuck in a cluster of players during a Raachad White run in the first quarter when safety Ji’Ayir Brown rolled over his right ankle.

“Any time you lose one of your best players, also a huge leader, obviously it’s a huge blow,” Shanahan told reporters, according to the Associated Press. “I feel bad for Fred right now. He was in good spirits. He has a good foundation.”

As trainers examined Warner, his 49ers teammates came onto the field from the sideline and then watched as his leg was placed into an aircast and drove him off the Raymond James Stadium field.

49ers running back Christian McCaffrey described the injury as “heartbreaking,” according to the AP.

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Warner, 28 and a third-round pick in 2018, had become the centerpiece of the San Francisco defense, which entered Sunday tied for the sixth-best mark in the league for points allowed per game (19.6) under defensive coordinator and former Jets head coach Robert Saleh.

The unit’s strong performance has helped the 49ers overcome a Brock Purdy injury — with their starting quarterback missing his fourth game Sunday with a toe injury — while adjusting to backup quarterback Mac Jones.

“It was sickening,” Bucs coach Todd Bowles said. “One of the best players in the league and a great guy. That breaks your heart. Hope he has a speedy recovery.”

San Francisco led the Buccaneers early but ended up losing 30-19, and falling to 4-2 — as Jones threw two interceptions while Tampa Bay quarterback Baker Mayfield collected 256 passing yards and two touchdowns.