Gary Cohn's sudden resignation as President Donald Trump's top economic adviser is rattling Wall Street.

US stock futures dropped sharply on Tuesday evening after Cohn announced plans to step down amid a disagreement with Trump over trade policy.

Losses are expected when US markets open for trading. S&P 500 futures were down 0.9% as of 3:45 a.m. ET, and Dow futures were down over 300 points, or 1.2%.

The negative reaction underlines how investors have long been reassured by Cohn's presence in the Trump administration. Many believed the former Goldman Sachs (GS) president was a moderating voice to Trump's more aggressive views on economic policy, especially trade.

"The market looked at Gary Cohn as being the counterbalance to a pure strain of nationalism on tariffs and trade," said Peter Kenny, chief global market strategist at Global Markets Advisory Group.

Cohn's exit from the White House also signals he may have lost a bruising fight with rivals inside the administration on tariffs. Cohn had been trying to soften Trump's plan to impose tariffs on aluminum and steel that some Republicans and business executives fear could spark a trade war.

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Trump's tariff announcement last week spooked Wall Street. The markets bounced back on Monday, when investors thought that House Speaker Paul Ryan and others would succeed in softening Trump's stance on tariffs.

"This trade issue really strikes fear into the market because it's an unknown," said Kenny. "It's a variable markets will have difficulty pricing in."

The worries extended to global stocks. After swinging between small gains and losses Wednesday morning, Tokyo's Nikkei shed 0.7% and Hong Kong's Hang Seng dropped over 1%.

Major European indexes opened with losses of less than 0.5%.

In his statement on Tuesday, Cohn said it's been an "honor to serve my country and enact pro-growth economic policies to benefit the American people."

Lloyd Blankfein, the CEO of Goldman Sachs, sent out a tweet on Tuesday crediting Cohn for his service and saying he is "disappointed to see him leave."

-- Jethro Mullen and Charles Riley contributed to this report.