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This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
GRIN2A (Glutamate Ionotropic Receptor NMDA Type Subunit 2A) is a Protein Coding gene. Diseases associated with GRIN2A include Epilepsy, Focal, With Speech Disorder And With Or Without Mental Retardation and Benign Epilepsy With Centrotemporal Spikes. Among its related pathways are Neuroscience and Nicotine addiction. Gene Ontology (GO) annotations related to this gene include calcium channel activity and ionotropic glutamate receptor activity. An important paralog of this gene is GRIN2B.
NMDA receptors are members of the ionotropic class of glutamate receptors, which also includes Kainate and AMPA receptors. NMDA receptors consist of NR1 subunits combined with NR2 (A-D) or NR3 (A-B) subunits. The ligand-gated channel is permeable to cations.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH16J010180 | Promoter/Enhancer | 1.8 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +0.9 | 927 | 2.8 | HNRNPL CTCF TEAD4 REST BACH1 LARP7 ZNF143 ZIC2 RAD21 IRF2 | GRIN2A piR-50241-003 | |
GH16J010120 | Enhancer | 0.9 | Ensembl ENCODE dbSUPER | 39.1 | +60.9 | 60926 | 2.8 | CTCF ZNF316 MAFF MAFK MAFG ARNT RAD21 FOS ATF7 JUND | GRIN2A ENSG00000261810 piR-50241-003 | |
GH16J010129 | Enhancer | 0.5 | dbSUPER | 32 | +52.4 | 52419 | 2.5 | ATF7 DPF2 ARNT PLRG1 ATF2 | GRIN2A piR-50241-003 | |
GH16J010361 | Enhancer | 1.2 | Ensembl ENCODE | 11.2 | -179.8 | -179773 | 2.6 | GATAD2A TFE3 ZNF512 LEF1 IKZF1 NFKBIZ JUND ZNF143 RBFOX2 PKNOX1 | ATF7IP2 HNRNPCP4 GRIN2A ENSG00000260756 piR-49097-040 lnc-ATF7IP2-3 EMP2 | |
GH16J010126 | Enhancer | 0.4 | FANTOM5 ENCODE | 33.8 | +55.9 | 55938 | 1 | GRIN2A ATF7IP2 piR-50241-003 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001540 | amyloid-beta binding | TAS | 26719327 |
GO:0004970 | ionotropic glutamate receptor activity | IEA | -- |
GO:0004972 | NMDA glutamate receptor activity | IEA,TAS | 17526495 |
GO:0005216 | ion channel activity | IEA | -- |
GO:0005261 | cation channel activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005783 | endoplasmic reticulum | IEA | -- |
GO:0005886 | plasma membrane | IEA,TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IDA | 26875626 |
GO:0008021 | synaptic vesicle | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Post NMDA receptor activation events | ||
3 | Circadian entrainment | ||
4 | Transmission across Chemical Synapses |
.62
|
|
5 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 |
.35
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001964 | startle response | IEA | -- |
GO:0001975 | response to amphetamine | IEA | -- |
GO:0006811 | ion transport | IEA | -- |
GO:0006816 | calcium ion transport | IEA | -- |
GO:0007215 | glutamate receptor signaling pathway | TAS | 8768735 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Felbamate | Approved | Pharma | Target, antagonist | 4 | ||
Memantine | Approved, Investigational | Pharma | Channel blocker, Target, antagonist | 214 | ||
Glycine | Approved, Vet_approved | Nutra | Agonist, Full agonist, Target, antagonist | 196 | ||
Meperidine | Approved | Pharma | Target, antagonist | 83 | ||
Glutamic acid | Approved | Nutra | Agonist, Full agonist, Target | 304 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
[<sup>3</sup>H]MK-801 |
|
|
|
|||
CGS19755 |
|
Antagonist |
|
|
||
MK-801 |
|
Channel blocker |
|
|
||
trifluoroacetic acid |
|
76-05-1 | ||||
Ifenprodil hemitartrate |
|
23210-56-2 |
|
|
Compound | Action | Cas Number |
---|---|---|
cis-ACPD | Potent NMDA agonist. Also group II mGluR agonist | 477331-06-9 |
HU 211 | NMDA receptor antagonist; also NF-kappaB inhibitor | 112924-45-5 |
Ibotenic acid | Non-selective NMDA agonist | 2552-55-8 |
Ifenprodil hemitartrate | Non-competitive NMDA antagonist. Also sigma ligand | 23210-56-2 |
L-Cysteinesulfinic acid | NMDA and mGlu agonist | 1115-65-7 |
Compound | Action | Cas Number |
---|---|---|
(-)-Huperzine A | NMDA receptor antagonist/AChE inhibitor | 102518-79-6 |
(-)-MK 801 | NMDA antagonist,potent and selective | 121917-57-5 |
(+)-MK 801 | Potent NMDA antagonist | 70449-94-4 |
(+)-MK 801 Maleate | Potent NMDA antagonist | 77086-22-7 |
(2R,3S)-Chlorpheg | 140924-23-8 | |
(R)-(+)-HA-966 | 123931-04-4 | |
(R)-4-Carboxyphenylglycine | 134052-68-9 | |
(R)-CPP | 126453-07-4 | |
(RS)-(Tetrazol-5-yl)glycine | 138199-51-6 | |
(RS)-CPP | 100828-16-8 | |
(S)-(-)-HA-966 | 111821-58-0 | |
5,7-Dichlorokynurenic acid | 131123-76-7 | |
5,7-Dichlorokynurenic acid sodium salt | 1184986-70-6 | |
ACBC | 22264-50-2 | |
Arcaine sulfate | 14923-17-2 | |
CCMQ | 132623-44-0 | |
CGP 37849 | 127910-31-0 | |
CGP 39551 | 127910-32-1 | |
CGP 78608 hydrochloride | 1135278-54-4 | |
CGS 19755 | 110347-85-8 | |
CIQ | 486427-17-2 | |
cis-ACPD | 477331-06-9 | |
Co 101244 hydrochloride | 193356-17-1 | |
Conantokin G | 93438-65-4 | |
Conantokin-T | 127476-26-0 | |
D-AP5 | 79055-68-8 | |
D-CPP-ene | 117414-74-1 | |
DL-AP5 | 76326-31-3 | |
DL-AP5 Sodium salt | 1303993-72-7 | |
DL-AP7 | 78966-69-5 | |
DQP 1105 | 380560-89-4 | |
Eliprodil | 119431-25-3 | |
Felbamate | 25451-15-4 | |
Felbamate hydrate | 1177501-39-1 | |
Flupirtine maleate | 75507-68-5 | |
Gavestinel | 153436-38-5 | |
GLYX 13 | 117928-94-6 | |
Homoquinolinic acid | 490-75-5 | |
HU 211 | NMDA antagonist, novel and non-competitive | 112924-45-5 |
Ibotenic acid | 2552-55-8 | |
Ifenprodil Tartrate | NMDA receptor antagonist | 23210-58-4 |
L-689,560 | potent NMDA antagonist | 139051-78-8 |
L-701,252 | 151057-13-5 | |
L-701,324 | 142326-59-8 | |
L-AP5 | 79055-67-7 | |
L-Cysteinesulfinic acid | 1115-65-7 | |
LY 233053 | 125546-04-5 | |
LY 235959 | 137433-06-8 | |
MDL-29951 | 130798-51-5 | |
Memantine hydrochloride | NMDA receptor antagonist | 41100-52-1 |
MNI-caged-D-aspartate | 845555-94-4 | |
MNI-caged-NMDA | 1227675-52-6 | |
N-(4-Hydroxyphenylacetyl)spermine | 130210-32-1 | |
N20C hydrochloride | 1177583-87-7 | |
NMDA (N-Methyl-D-aspartic acid) | NMDA receptor agonist | 6384-92-5 |
PMPA (NMDA antagonist) | 113919-36-1 | |
PPDA | 684283-16-7 | |
PPPA | 113190-92-4 | |
QNZ 46 | 1237744-13-6 | |
Quinolinic acid | 89-00-9 | |
Remacemide hydrochloride | 111686-79-4 | |
Ro 04-5595 hydrochloride | 64047-73-0 | |
Ro 8-4304 hydrochloride | 1312991-77-7 | |
SDZ 220-040 | 174575-40-7 | |
SDZ 220-581 | NMDA glutamate receptor subtype antagonist | 174575-17-8 |
SDZ 220-581 hydrochloride | NMDA receptor antagonist | 179411-93-9 |
Spermidine trihydrochloride | 334-50-9 | |
Spermine tetrahydrochloride | 306-67-2 | |
Synthalin sulfate | 182285-12-7 | |
TCN 201 | 852918-02-6 | |
TCN 213 | 556803-08-8 | |
TCN 237 dihydrochloride | 700878-19-9 | |
TCS 46b | 302799-86-6 | |
threo Ifenprodil hemitartrate | 1312991-83-5 | |
ZD 9379 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | GRIN2A 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | GRIN2A 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | GRIN2A 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Grin2a 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Grin2a 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | GRIN2A 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | GRIN2A 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | GRIN2A 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | GRIN2A 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | grin2a 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | grin2aa 30 31 |
|
OneToMany | |
grin2ab 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Nmdar2 32 |
|
|
SNP ID | Clinical significance and condition | Chr 16 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
638905 | Uncertain Significance: Epilepsy, focal, with speech disorder and with or without mental retardation | 9,834,112(-) | T/G | MISSENSE_VARIANT | |
639911 | Uncertain Significance: Epilepsy, focal, with speech disorder and with or without mental retardation | 9,849,776(-) | ACATGGCACGGTGTTC | INFRAME_INDEL | |
640659 | Pathogenic: Epilepsy, focal, with speech disorder and with or without mental retardation | 9,841,099(-) | G/T | NONSENSE | |
641063 | Uncertain Significance: Epilepsy, focal, with speech disorder and with or without mental retardation | 9,764,068(-) | C/G | MISSENSE_VARIANT | |
641065 | Uncertain Significance: Epilepsy, focal, with speech disorder and with or without mental retardation; not provided | 9,849,813(-) | G/T | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
epilepsy, focal, with speech disorder and with or without mental retardation |
|
|
benign epilepsy with centrotemporal spikes |
|
|
rolandic epilepsy-speech dyspraxia syndrome |
|
|
early-onset epileptic encephalopathy and intellectual disability due to grin2a mutation |
|
|
alacrima, achalasia, and mental retardation syndrome |
|