Having not used Keyclone for a few years, I won't be able to help that much.

With IS Boxer, using the mouse works best like this:
a) Use the mouse action, as the trigger.
b) Have the software send a key combination to the game.
c) Have that key combination trigger whatever.

Using scroll wheel up, as a bind in the game, is not consistent.
But using scroll wheel up, to trigger the software to send Alt + Shift + R to the game, and having that bound to do whatever works great.

That might be the case with KC too.