Senate Majority Leader John Thune has one of the toughest jobs in Washington. It could get even harder next year.Why it matters: Thune is one of the few Republicans in Washington who's managed to say "no" to President Trump and still keep his job. But the Senate leader could enter the next Congress with diminished power, leading a conference whose loyalty increasingly lies with Trump.Republican control of Congress could be weakened, if not lost. The Senate's MAGA flank is poised to grow. And Trump — who has been relatively restrained in his criticism of Thune even as his demands to pass the SAVE America Act and kill the filibuster remain unmet — will have nothing to lose in the last two years of his presidency.Zoom in: The Senate Republican Conference itself is poised for a drastic power shift away from the institutionalist wing led by Thune.Moderate voices like Sens. John Cornyn (Texas), Thom Tillis (N.C.) and Bill Cassidy (La.) will be gone after being forced out by Trump. Sen. Susan Collins (Maine) also faces a tough reelection fight.Thune chose four senators to be in his original leadership inner circle: Steve Daines (Mont.), Markwayne Mullin (Okla.), Cornyn and Marsha Blackburn (Tenn.). They'll all likely be gone next year.What to watch: Meanwhile, hardline conservatives and MAGA voices are gaining power.Senators who've long been thorns in leadership's side have all ascended to committee chairmanships: Rick Scott (Fla.) on the Aging Committee (he also helms the conservative GOP steering committee), Ron Johnson (Wis.) on the Budget Committee, and Rand Paul on Homeland Security.Sen. Mike Lee (Utah) is in position to lead the powerful Judiciary Committee next year, putting the online MAGA favorite in charge of judicial nominations — including any to the U.S. Supreme Court.A surge of House-bred MAGA energy is also on its way. Conservative members like Reps. Barry Moore (Ala.), Kevin Hern (Okla.) and Harriet Hageman (Wyo.) are all but certain to join the upper chamber."Hopefully, they get to the Senate and maintain their fervor from the House in wanting the Senate to move and act differently and help shake it up," Sen. Jim Banks (R-Ind.) told Axios about the incoming class.Finally, there's firebrand Texas AG Ken Paxton, who defeated Cornyn in a primary. Paxton is a slight favorite to win the deep-red seat despite enormous baggage.Between the lines: The shifting politics could result in more intra-party fighting for Thune to navigate.He could face more pressure to vote on partisan bills, push through controversial nominees or do away with the filibuster.And it will make nuts-and-bolts legislation, like funding the government, anything but routine.Zoom out: The worst scenario for Thune, of course, is that he ends up in the minority. The GOP's Senate majority, once considered safe, can no longer be taken for granted.But if Republicans hang on in the Senate and Democrats take the House, Thune could be forced to deal with another Trump impeachment trial.Getting anything done will be close to impossible.The bottom line: Even if Thune keeps his majority, the center of gravity in the Senate GOP is shifting beneath him.