Greens co-leader Patrick Harvie accused the EHRC of “creating confusion and encouraging overt transphobia” as a coalition of LGBT groups sought to revoke the commission's status as an independent body.
Twenty LGBT organisations, including Stonewall, claim the commission is working to remove legal protections for trans people.
A 19-page submission to the United Nations, which the groups say was prompted by the EHRC’s stance on trans rights, asks for the independent status of the body to be reviewed.
But EHRC chief executive Marcial Boo said: “Stonewall and other critics are aiming at the wrong target.
“The EHRC has the power to prosecute people and companies that discriminate against trans people. We have done so.
“Instead of criticising the statutory regulator that exists to protect the rights of everyone in Britain, campaign groups should work with us to identify discrimination against LGBT people so we can take action together to stop it.”
Earlier, a spokesperson for the EHRC told the BBC it takes all decisions impartially and “based on evidence in the UK and internationally”.
The LGBT groups criticised the EHRC’s recent intervention on the Scottish Government’s bid to reform the Gender Recognition Act (GRA).
The groups said: “Their recent statements on GRA reform in Scotland, and the conversion therapy ban in England and Wales, not only reverse their long-held positions, but are in stark contrast to international human rights standards.
“The EHRC’s stance seeks to strip trans people of legal protections and pose a grave threat to the ability of trans people to participate in daily life with dignity and respect.”
The submission accuses the EHRC of lacking independence from the UK Government, which it says influences appointments on the body and has politicised its positions.
Without the status, organisations cannot participate at the UN Human Rights Council.
Last month, the EHRC was criticised by LGBT organisations after it said plans to change the law on gender recognition in Scotland required “further consideration”.
In a statement posted on Twitter, Mr Harvie – the Scottish minister for zero carbon buildings, active travel and tenants' rights – said: “If the leaks are true and the EHRC does try this, I am certain it will be strongly opposed in Scotland.
"But the harm is already done; both creating confusion and encouraging overt transphobia. The EHRC has become a weapon in the UK Govt's culture war. It has lost all credibility.”
Scottish Government ministers have tabled proposals to reform the Gender Recognition Act to make it easier for people to change their legally recognised gender, with a Bill expected at Holyrood this year.
But the EHRC said “further consideration is needed before any change to the law should be made”.
A spokesperson for the body said “everyone’s concerns should be discussed and addressed carefully, openly and with respect to avoid further damage and division”, but insisted more time is needed.
Stonewall, a leading LGBT group which is a signatory on the submission to the UN, said the EHRC’s statement was an attack on trans equality and that it is “deeply troubled” by the approach the group is taking to trans people’s human rights.