It's what you don't know that is happening, that has the biggest impact on your business.
Or
It's what you don't know is happening, that has the biggest impact on your business
Only the second sentence is correct. It helps to rewrite the sentence to see this. It's the things ( that ) you don't know are happening, that have the biggest impact on your business.
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Only the second sentence is correct.
It helps to rewrite the sentence to see this.
It's the things (that) you don't know are happening, that have the biggest impact on your business.
(that) is optional but when used it has to immediately follow the head noun and it can't be used after the you don't know part.