I have two ASUS dual CPU workstation motherboards and run some of the devices with PCIe ribbon extensions. I cannot run my Highpoint U.2 RAID card on an extension but I can run a Highpoint USB 3 card just fine. I can run a 2070 GPU just fine, but the RTX A5000 GPUs are flakey. The dual Blackmagic quad 4k capture cards want to be in specific motherboard slots and work okay on one particular brand (Thermaltake) of extension cable.
The problem is nuanced.
I found some ultra low profile pcie extensions (basically mining risers that use a USB3 cable) that allow me to relocate the cards elsewhere but still install them in slots that are under big GPU fans.
This was the one I used: https://www.amazon.com/dp/B07N38Y799
In fact, some even clock in at 4.3 slots. https://www.asus.com/Motherboards-Components/Graphics-Cards/...
On AM4 ATX-boards slot 0 is often then primary M.2 slot. Slot 1 the GPU and slot 2 is either empty, or the CMOS battery, or like you suggested a secondary M.2.
So you're already down to a maximum of 5 PCIe slots.
I had to resort to a mining rig style setup with 16 lane extenders to be able to properly utilize all the slots after running into the same issue.