We perform specialized assays on the cDNA encoding human NMDA receptor subunits into which a single base pair change has been inserted to reproduce a genetic variant found in one or more patients. We perform in vitro experiments using this recombinant cDNA to determine how this genetic change alters important functional properties of the NMDA receptor. The data helps understand the overall impact of GRIN variations for the community and could be used in the future to develop new therapeutic strategies.
To verify whether a particular genetic variant has already been functionally characterized, go to the GRIN Portal and select “Variant Classification” and enter the gene and protein (p.) or DNA (c.) variant information into the search. All complete data will be available there.
GRIN Registries
We strongly encourage all families with a patient who has a GRIN variant to join one of two harmonized GRIN Registries:
Families located in the United States
If you reside in the US, you can join the GRIN registry through the following email address.
In addition, for families in the US that are interested in understanding variant characterization, variant analysis, and genetic counseling, you are encouraged to take advantage of the following free service for GRIN NDD families. Information about this service can be found at InformedDNA.
Families in LATAM, Canada or Australia can join the GRIN Registry and reach out at the following email address: grinresearch@cuanschutz.edu
Families located in the EU, Asia, and Africa
You can join the GRIN Registry.
For Clinicians and Research Scientists
Upon checking the GRIN Portal, if the functional report for a missense variant has not been reported/uploaded, you can contact Harry Gerard to see if or where the variant currently is in the CFERV characterization pipeline. Variant testing is not guaranteed for new variants, given the work is currently not funded by the National Institutes of Health (NIH) or any clinical unit. It depends on CFERV time and resources and can take several months, if it proceeds. Financial donations to advance testing for specific or unspecified variants are welcome and greatly appreciated.
Ongoing Clinical Trials
GRIN Therapeutics is currently running a Phase 3 pivotal precision medicine trial, in which an NMDA receptor inhibitor is given to only patients with a variant that renders NMDA receptors overactive (i.e. gain-of-function).
All inquiries about variant characterization must go through informed DNA in the US or through one of the clinical sites in other countries, which can be coordinated through the Leipzig directory.