Downing Street said it was looking into "very concerning" reports about the Tehran airliner crash following speculation in the media that the jet was shot down by a missile.
Boris Johnson used a phone call with Ukrainian President Volodymyr Zelenskyy to call for a "full, credible and transparent investigation" following the plane crash.
Asked whether there were any concerns about the cause of the disaster, a Number 10 spokesman said: "I'm not going to speculate on this but the reports we have seen are very concerning and we are urgently looking into them."
Three Britons were among the dead after Ukraine International Airline (UIA) plane crashed moments after take-off from Iran, with investigators focused on how the aircraft fell out of the sky.
The Iranian military had disputed suggestions the airliner was brought down by a missile, with officials in Iran blaming an engine fire.
The victims included engineer Sam Zokaei, from Surrey, Saeed Tahmasebi Khademasadi, from west London, and Mohammad Reza Kadkhoda Zadeh, from near Brighton.
All three were named on the list of 167 passengers on board flight PS752 by Ukraine International Airlines (UIA), which crashed moments after it left Imam Khomeini International Airport in Tehran at 6.10am local time (2.40am GMT) on Wednesday, bound for the Ukrainian capital Kyiv.
The Prime Minister pushed for the facts to be established during his conversation with Mr Zelenskyy on Thursday.
Mr Zelenskyy ordered a criminal investigation soon after the details of the tragedy emerged this week.
The airline ruled out human error, and crew were not said to have made an emergency call.
The crash comes amid escalating tension in the Persian Gulf following the killing last week of Iranian general Qassem Soleimani by the US, prompting several airlines to reroute flights away from Tehran's airspace.
Iran fired missiles at army bases in Iraq were both US and UK troops were stationed, although both Number 10 and the White House said there had been no casualties incurred.
A Downing Street spokesperson said: "He offered his condolences to the president for the loss of the Ukraine International Airlines plane and for all those who were on board.
"President Zelenskyy updated the Prime Minister on Ukrainian efforts to establish the facts and the Prime Minister offered UK support.
"The Prime Minister said that there needed to be a full, credible and transparent investigation into what happened."
During his conversation Mr Johnson also "underlined the UK's continued commitment to Ukrainian sovereignty" with tension over territory continuing to bristle between the eastern European country and Russia.