GRIN2A

Highest pathogenic variant AF is 0.000013133874

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000396573

Coding exons

12

Length

424236

Individuals with no LoFs

125742

Homozygous LoFs

0

Heterozygous LoFs

6

Defined

125748

p

0.0000239

Function

FUNCTION: Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28105280). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B (PubMed:26919761, PubMed:26875626). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:Q00959, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:8768735}.;

Disease

DISEASE: Epilepsy, focal, with speech disorder and with or without mental retardation (FESD) [MIM:245570]: A highly variable neurologic disorder with features ranging from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and mental retardation to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, mental retardation and speech dyspraxia, and benign epilepsy with centrotemporal spikes. {ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23933818, ECO:0000269|PubMed:23933819, ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:24504326, ECO:0000269|PubMed:24903190, ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28182669}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2).; DISEASE: Note=GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma. {ECO:0000269|PubMed:21499247, ECO:0000269|PubMed:24455489}.;