Scope

CFERV evaluates whether glutamate receptor function is altered by rare genetic variants within the associated family of human genes, GRIN (7), GRIA (4), GRIK (5) and GRID (2).  These genes encode ligand-gated ion channels known as NMDA, AMPA, KA, and delta receptors, which play essential roles in brain function.  Thus, mutations can play a causative role in neurological disorders and disease.

Rare variants in one or more of these genes (see Table) have been identified in patients with epilepsy syndromes, intellectual disability, developmental delay, autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder, hypotonia, cerebral visual impairment, and other conditions.

CFERV accepts requests to evaluate patient-associated rare variants that include missense, nonsense, frameshift, or internal protein coding deletions.  All requests are carefully considered and when selected for study, the mutation is introduced into a human cDNA encoding the target subunit and receptor function is then evaluated in a series of electrophysiology and biochemistry studies. 

Genes

Chromosomes

Protein Subunits

Endpoints measured

GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B

9q34.3, 16p13.2, 12p12, 17q25, 19q13.1-qter, 9q31.1, 19p13.3

GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A, GluN3B

Agonist glutamate potency (EC50)
Agonist glycine potency (EC50)
Mg2+ and Zn2+ inhibition potency (IC50)
pH (proton) inhibition (%)
Channel open probability (Popen)
Glutamate synaptic-like response time course (deactivation tw, msec)
Receptor cell surface expression/trafficking (%)
(note: endpoints reported may vary depending on the gene involved in the study)

GRIA1, GRIA2, GRIA3, GRIA4

5q31.1, 4q32-q33, Xq25-q26, 11q22

GluA1, GluA2, GluA3, GluA4

GRIK1, GRIK2, GRIK3, GRIK4, GRIK5

21q22.11, 6q16.3-q21, 1p34-p33, 11q22.3, 19q13.2

GluK1, GluK2, GluK3, GluK4, GluK5

GRID1, GRID2

10q22, 4q22

GluD1, GluD2