CASK gene mutations

What we know about CASK

Which proteins does CASK interact with?

In the pre-synapse

CASK regulates the synaptic vesicle exocytosis and neuronal cell adhesion through a tripartite complex with VELI1 (LIN7A) and MINT1 (APBA1). In Knock Out mice, Mint and neurexin levels are lower

The tripartite complex is unaffected in XL-ID individuals and MICPCH caused by missense mutations.

CASK binds to neurexin (which binds to Neuroligin 1). As a result neuroligin levels are found to be higher in CASK mutant cells.


Which genes does CASK regulate?

Reduced CASK levels have been seen to affect the transcription of pre-synaptic genes


CASK directly interacts with NRXN1 – a gene associated with neurodevelopmental disorders. CASK gene mutations down-regulate NRXN1. Research has shown that the CASK–NRXN1 interaction is disrupted in MICPCH.


TBR1 is a causative gene for autism. 

The binding of CASK to TBR1 in the nucleus facilitates the transcription of T-element-containing genes, such as Reelin and GluN2B (NMDA glutamate receptor subunit).  In MICPCH, The resultant down-regulation of GluN2B probably causes disruption of synaptic E/I balance.

It has been found that mice with a CASK mutation have less CASK-TBR1 interaction and so MICPCH reduces the TBR1-GRIN2B pathway.

More information on CASK gene disorders...