The Trigana Air Service plane was flying from Papua's provincial capital, Jayapura, to the Papua city of Oksibil when it lost contact with Oksibil's airport, said Transportation Ministry spokesman Julius Barata.
There was no indication that the pilot had made a distress call, he said.
The ATR42-300 twin turboprop plane was carrying 49 passengers and five crew members on the scheduled 42-minute journey, Barata said. Five children, including two infants, were among the passengers.
Oksibil, which is about 280 kilometers (175 miles) south of Jayapura, was experiencing heavy rain, strong winds and fog when the plane lost contact with the airport minutes before it was scheduled to land, said Susanto, the head of Papua's search and rescue agency.
Residents of Okbape village in Papua's Bintang district told local police that they saw a plane flying low before crashing into a mountain, said Susanto, who like many Indonesians goes by one name.
He said about 150 rescuers were heading to the remote area, which is known for its dense forest and steep cliffs, and would begin searching for the plane early in the morning.
"We are now working closely with the National Search and Rescue Agency to find the plane," said Transport Minister Ignasius Jonan.
A plane was sent yesterday to look for the missing airliner, but the search was suspended due to darkness and limited visibility and will resume in the morning, Susanto said.
Much of Papua is covered with impenetrable jungles and mountains. Some planes that have crashed there in the past have never been found.
European plane maker ATR said in a statement yesterday that it "acknowledges the reported loss of contact" with the Trigana flight "and is standing by to support the relevant aviation authorities." An ATR spokesman would not comment further.
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