Table 1.
Summary of GRIN1 mutations identified in epilepsy
| GRIN1 | Protein (cases) | Gene | Zygosity | Origin | Location | Functional validation | Consequences | Phenotype | References |
|---|---|---|---|---|---|---|---|---|---|
| Duplication (1) | p.Ser560dup | c.1679_1681dupGCA | Het | De novo | S1-M1 linker | Receptor activity↓ | LOF | Partial complex epilepsy + Severe ID + CVI | [22, 25] |
| Nonsense (1) | p.Gln556* (3) | c.1666C>T | Homo | Inherited | S1-M1 linker | Nonfunctional | LOF | Fatal EE (3) | [22] |
| Missense (10) | p.Ser549Arg | c.1654A>C | Het | De novo | S1-M1 linker | Epilepsy + Severe ID + MD | [22, 23] | ||
| p.Asp552Glu (2) | c.1656C>A | Het | De novo | S1-M1 linker | Current↓, Glu↓, Gly↓ | LOF | GTCS + Severe ID | [23, 26] | |
| c.1656C>A | Het | De novo | Epilepsy + Severe ID + MD + CVI | [22] | |||||
| p.Met641Ile | c.1923G>A | Het | De novo | M3 | Epilepsy + Severe ID + MD | [22, 23] | |||
| p.Ala645Ser | c.1933G>T | Het | De novo | M3 | → | No change | Epilepsy + Severe ID + CVI | [22, 23] | |
| p.Tyr647Ser | c.1940A>C | Het | De novo | M3 | Maximal agonist-inducible currents↓ | LOF | IS + Severe ID | [22, 27] | |
| p.Asn650Lys | c.1950C>G | Het | De novo | M3 | Epilepsy + Severe ID + MD | [22, 23] | |||
| p.Ser688Tyr | c.2063C > A | Het | De novo | LBD (S2) | EOEE + Hyperkinetic and oculogyric-like movements | [24] | |||
| p.Gly815Arg (4) | c.2443G>A | Het | De novo | M4 | Maximal agonist-inducible currents↓, Glu↓ | LOF | Epilepsy + Severe ID + MD | [23] | |
| c.2443G>A | Het | De novo | Epilepsy + Severe ID + MD + CVI (2) | [22] | |||||
| c.2444G>T | Het | De novo | Epilepsy + Severe ID + MD | [22] | |||||
| p.Gly827Arg (4) | c.2479G>A | Het | M4 | Nonfunctional | LOF | Epilepsy + Severe ID + MD | [22] | ||
| c.2479G>A | Het | De novo | Epilepsy + Severe ID + MD | [22] | |||||
| c.2479G>A | Het | De novo | Severe ID + MD | [22] | |||||
| c.2479G > A | Het | De novo | EOEE+ Hyperkinetic and oculogyric-like movements | [24] | |||||
| p.Arg844Cys (2) | c.2530C>T | Het | De novo | CTD | → | No change | Epilepsy + Severe ID + MD (2) | [22] |
CTD C-terminal domain, CVI cortical visual impairment, EE epileptic encephalopathy, EOEE early-onset epileptic encephalopathy, Het heterozygous, Hom homozygous, ID intellectual disability, LBD ligand-binding domain, LOF loss-of-function, M1-4 transmembrane domain 1-4, MD movement disorder, S1-2 S1 and S2 segment of ligand binding domains
↓ Decrease, → no change