A medical fluid flow control system comprises an interface including a pump actuator port and a pump seal port, a membrane gasket including a pump actuation area and a pump aperture, and a pumping cassette including a flexible sheet and defining a pump chamber, a pump portion of the flexible sheet covering the pump chamber. The pump seal port is operable with the pump aperture to seal the pump portion of the flexible sheet to the pump actuation area of the membrane gasket and the pump actuator port is configured to move the pump portion of the flexible sheet and the pump actuation area of the membrane gasket at the pump chamber of the cassette.