GRIN Variants Database:
In the last years, high-throughput genetic studies and research groups provided valuable information on GRIN variants genotype-phenotype association (pathogenicity and clinical symptoms), as well as the functional annotation of a growing number of GRIN variants. Nevertheless, the information is highly fragmented, partially redundant and non-curated. Further, the growing number of families with a GRIN variant diagnosis urges the acceleration of both bioinformatic and experimental approaches to provide a molecular diagnosis (e.g. functional annotation of GRIN variants).
The GRIN Database (GRINdb) is a unified, non- redundant curated database with all available information on GRIN variants. The Genetic, Clinical and Functional Information of all reported GRIN variants has been collected from ClinVar, LOVD, Gnomad, Uniprot, as well as from the databases from GRIN research reference groups (Center for functional evaluation of rare variants, Emory University, CFERV; University of Leipzig, GRIN-Leipzig and Barcelona GRIN team, BCN-GRIN. Besides automatically collecting GRIN variants, GRIN database provides a manual curation of GRIN variants-associated data and providing the functional stratification (e.g. gain/loss-of-function) upon functional annotation availability.
GRIN variants query
GRIN database provides a user-friendly interface oriented to clinicians and researchers searching for the potentially existing information on a specific GRIN variant. By providing the nucleotide change (using HGVS nomenclature) or the amino acid change, the user can retrieve all the available information above mentioned. Upon query submission, GRIN database automatically provides an output displaying i) GRIN variant pathogenicity (e.g. neutral/disease causing/uncertain pathogenesis), ii) experimental functional annotations and cell-based assays employed, iii) clinical phenotype/s, iv) variant classification (e.g. loss/gain-of-function, upon availability) and a NGL viewer display interactively depicting the affected amino acid (GRIN missense variants) within the NMDA receptor molecular model.
The user can also display all variants for individual or multiple GRIN genes (selecting one or several GRIN genes), for a specific amino acid, for a specific position, or either combining the aforementioned searches. This search tool is particularly relevant for GRIN variants stratification and future clinical trials.
GRIN variants submission
Link To The Database:
If you want to support functional analysis for GRIN disorders and in that way contribute to the expansion of this database, please do so through this link from the Hospital Clinic in Barcelona: https://dona.clinicbarcelona.org/cpn/reptes?id=Diagnostico-funcional-para-pacientes-GRIN
The GRIN Portal is a coalition of investigators seeking to aggregate and harmonize data generated to study GRIN-related disorders, and to make summary data interactively accessible for the wider scientific community, while providing educational resources for everyone. The goals of this project are:
- Providing information on GRIN-related disorders
- Supporting research on GRIN-related disorders
- Facilitating recruitment of individuals to the global GRIN registry
- Providing support in variant interpretation and classification
- Visualizing data from the global GRIN registry
- Linking researchers, clinicians and families
The project is overseen by Johannes Lemke (contact PI), Steve Traynelis (contact PI), Tim Benke and Dennis Lal. This GRIN Portal is an ongoing project and interested collaborators are invited to reach out to join the project.