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Kim Sang Duk, also known as Tony Kim, was teaching at Pyongyang University of Science and Technology, a statement from the school said.
Kim is the third US citizen in North Korean custody. The school said he was detained by authorities at the airport "after several weeks of service, teaching at PUST."
"We understand this detention is related to an investigation into matters not connected in any way with the work of PUST," the school said.
"We cannot comment on anything that Mr. Kim may be alleged to have done that is not related to his teaching work on the PUST campus."
The statement said "life on campus and the teaching at PUST is continuing as normal" for the spring semester.
The detained American is a professor, the South Korea's Yonhap News Agency reported.
State Department, Swedish Embassy to work on case
The detention was also confirmed by Martina Aberg, deputy chief of mission at the Swedish Embassy in Pyongyang.
The embassy represents US interests in North Korea, since Washington and Pyongyang do not have direct diplomatic relations.
"He was prevented from getting on the flight out of Pyongyang," Aberg said. "We don't comment further than this."
The US State Department on Sunday said it was working on the case.
"We are aware of reports that a US citizen was detained in North Korea," said a department official. "The protection of US citizens is one of the Department's highest priorities."
The official said the United States would work with the Swedish Embassy on the matter, but did not provide further comment.
At least two other US citizens are known to be in North Korean custody.
Other US citizens freed
Since 2013, at least two other US citizens and a British journalist have also been detained for shorter periods and then released.
All of them were grabbed by North Korean security forces as they attempted to fly out of Pyongyang airport.
Merril Newman, who at the time of his October 2013 detention was an 85-year-old US veteran of the Korean War, was released two months later after a videotaped apology. American Jeffrey Fowle spent five months in detention in 2014 for allegedly leaving a Bible at a club for foreign sailors.
And last May, North Korean security officers detained BBC reporter Rupert Wingfield-Hayes as he was about to fly out of the country. He was interrogated for at least 10 hours and accused of defaming the Korean nation before eventually being released.
Korean Peninsula tensions
The US and Chinese governments have repeatedly warned the North Korean regime not to conduct a sixth nuclear weapons test. Pyongyang says it has the right to develop nuclear weapons.
South Korea and Japan -- both key US allies in the region -- have condemned frequent North Korean missile launches that are all banned under United Nations Security Council resolutions.
Washington recently dispatched the USS Carl Vinson aircraft carrier strike group to the region as a warning to Pyongyang.