TABLE 13.
Summary of genetic variants in iGluR genes
RVIS is the Residual Variation Intolerance Score given as a percentile rank among all genes (Petrovski et al., 2013) (http://genic-intolerance.org/). An RVIS score of 2.55 (e.g., GRIA1) means that 97.45% of all genes have more variation in the healthy population than GRIA1. All variants counted for this table were not present in healthy individuals (gnomAD database; evaluated on July 02, 2020). Many variants have multiple phenotypes, and this table is only a snapshot of the current literature, which is disproportionally weighted by different diagnostic procedures. “Others” includes large-scale chromosomal deletion, translocation, inversion, and duplication.
| Gene | Protein | RVIS | Variant types | Locations | Phenotypes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Missense | Nonsense | Frame shift | Splice | Other | ATD | ABD | TMD-linker | CTD | EPI | ID | ASD | ADHD | MD | SCZ/BP | |||
| % | |||||||||||||||||
| GRIA1 | GluA1 | 2.55 | 12 | 1 | 2 | 0 | 0 | 6 | 4 | 5 | 0 | 0 | 11 | 1 | 0 | 0 | 0 |
| GRIA2 | GluA2 | 10.8 | 19 | 1 | 3 | 2 | 6 | 6 | 2 | 16 | 0 | 9 | 30 | 17 | 1 | 5 | 0 |
| GRIA3 | GluA3 | 5.49 | 32 | 2 | 3 | 0 | 9 | 7 | 10 | 20 | 0 | 5 | 29 | 6 | 0 | 3 | 0 |
| GRIA4 | GluA4 | 4.57 | 6 | 0 | 0 | 0 | 0 | 0 | 2 | 4 | 0 | 3 | 5 | 0 | 0 | 2 | 0 |
| GRIK1 | GluK1 | 14.3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| GRIK2 | GluK2 | 7.78 | 11 | 2 | 1 | 5 | 2 | 5 | 1 | 7 | 1 | 3 | 10 | 1 | 1 | 1 | 2 |
| GRIK3 | GluK3 | 4.91 | 2 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| GRIK4 | GluK4 | 13 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| GRIK5 | GluK5 | 21.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| GRIN1 | GluN1 | 6.92 | 86 | 4 | 1 | 0 | 0 | 15 | 24 | 45 | 7 | 27 | 38 | 4 | 0 | 21 | 3 |
| GRIN2A | GluN2A | 1.96 | 209 | 24 | 36 | 13 | 29 | 67 | 82 | 50 | 80 | 203 | 190 | 19 | 5 | 28 | 5 |
| GRIN2B | GluN2B | 1.28 | 194 | 22 | 22 | 6 | 14 | 39 | 65 | 56 | 78 | 99 | 187 | 35 | 2 | 10 | 5 |
| GRIN2C | GluN2C | 62 | 13 | 1 | 5 | 0 | 0 | 6 | 5 | 1 | 7 | 1 | 4 | 8 | 0 | 0 | 7 |
| GRIN2D | GluN2D | 11.7 | 27 | 0 | 0 | 1 | 0 | 3 | 8 | 9 | 7 | 13 | 13 | 5 | 0 | 0 | 9 |
| GRIN3A | GluN3A | 67.6 | 11 | 2 | 0 | 0 | 0 | 7 | 3 | 1 | 2 | 0 | 1 | 5 | 0 | 0 | 4 |
| GRIN3B | GluN3B | 98.8 | 6 | 0 | 2 | 0 | 0 | 1 | 3 | 1 | 3 | 0 | 0 | 2 | 0 | 4 | 2 |
| GRID1 | GluD1 | 4.21 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| GRID2 | GluD2 | 8.77 | 5 | 2 | 0 | 0 | 3 | 3 | 0 | 4 | 0 | 0 | 1 | 2 | 0 | 7 | 1 |
TMD-linker, transmembrane domains (M1-4) and linker regions (S1-M1, M1-M2, M2-M3, M3-S2, and S2-M4); ADHD, attention deficit hyperactivity disorder; ASD, autism spectrum disorder; BP, bipolar disorder; Epi, epilepsy/seizures; ID, intellectual disability; MD, movement disorders; SCZ/BP, schizophrenia/bipolar.