GRIN2A

GRIN2A
Estructuras disponibles
PDB	Búsqueda ortóloga: PDBe RCSB
Lista de codigos id de PDB
	3NFL, 5H8Q, 5H8H, 5H8N, 5H8F, 5I2N, 5I2K, 5KDT, 5KCJ
Identificadores
Alias	GRIN2A, EPND, FESD, GluN2A, LKS, NMDAR2A, NR2A, glutamate ionotropic receptor NMDA type subunit 2A
IDs externos	OMIM: 138253 MGI: 95820 HomoloGene: 645 GeneCards: GRIN2A
Enfermedades genéticamente relacionadas
	hepatitis B, Síndrome de Landau-Kleffner, rolandic epilepsy-speech dyspraxia syndrome, benign epilepsy with centrotemporal spikes
Targeted by Drug
	glicina, ácido aspártico, homoquinolinic acid, Tetrazolylglycine, NMDAR, 5,7-dichlorokynurenic acid, Midafotel, selfotel, Amantadina, dizocilpine, ketamina, fenciclidina, Lanicemina, neboglamine, priralfinamide, esketamina, ketamina, CNS-5161, (RS)-ketamine hydrochloride, amantadine hydrochloride, orphenadrine citrate
Ontología génica
Función molecular	• calcium channel activity; • zinc ion binding; • NMDA glutamate receptor activity; • metal ion binding; • ion channel activity; • GO:0001948, GO:0016582 unión a proteína plasmática; • ionotropic glutamate receptor activity; • cation channel activity; • extracellularly glutamate-gated ion channel activity; • amyloid-beta binding; • glutamate-gated calcium ion channel activity; • signaling receptor activity;
Componente celular	• componente integral de membrana; • postsynaptic membrane; • membrana; • Vesícula sináptica; • GO:0097483, GO:0097481 postsynaptic density; • membrana plasmática; • sinapsis; • integral component of plasma membrane; • NMDA selective glutamate receptor complex; • cell surface; • unión celular; • retículo endoplasmático; • proyección neuronal; • presynaptic membrane; • postsynaptic density membrane; • integral component of postsynaptic density membrane; • synaptic membrane; • glutamatergic synapse; • cell projection; • Espina dendrítica;
Proceso biológico	• visual learning; • GO:0034613 protein localization; • glutamate receptor signaling pathway; • neurogénesis; • susto; • regulation of sensory perception of pain; • positive regulation of long-term synaptic potentiation; • GO:1903363 negative regulation of protein catabolic process; • response to amphetamine; • regulación de potencial de membrana; • directional locomotion; • modulation of chemical synaptic transmission; • memoria; • serotonin metabolic process; • ion transport; • aprendizaje; • cation transmembrane transport; • MAPK cascade; • regulation of synaptic plasticity; • sueño; • dopamine metabolic process; • ionotropic glutamate receptor signaling pathway; • response to wounding; • calcium ion transmembrane transport; • locomoción; • potencial postsináptico; • Potencial excitatorio postsináptico; • aprendizaje o memoria; • positive regulation of apoptotic process; • nocicepción; • response to ethanol; • calcium ion transport; • Potenciación a largo plazo; • transmisión sináptica química; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • ion transmembrane transport; • regulation of ion transmembrane transport; • GO:0015915 transporte; • desarrollo cerebral; • calcium-mediated signaling; • activation of cysteine-type endopeptidase activity; • GO:0060401 calcium ion transmembrane import into cytosol; • excitatory chemical synaptic transmission; • protein localization to postsynaptic membrane; • cellular response to amyloid-beta; • regulation of NMDA receptor activity;
	Fuentes: Amigo / QuickGO
Patrón de la expressión del ARN
	Más referencias a datos de expressión
Ortólogos
	2903
	14811
	ENSG00000183454
	ENSMUSG00000059003
	Q12879
	P35436
	NM_000833; NM_001134407; NM_001134408
	NM_008170
	NP_000824; NP_001127879; NP_001127880
	NP_032196
	Wikidata
Ver/Editar Humano	Ver/Editar Ratón

El receptor ionotrópico de glutamato, subunidad épsilon-1 [NMDA], es una proteína de vital importancia para la señalización cerebral normal, la plasticidad sináptica y la memoria. En humanos está codificada por el gen GRIN2A. La isoforma canónica de la subunidad GluN2A, con 1464 aminoácidos, es grande. Las isoformas cortas de GluN2A específicas de los primates pueden producirse mediante empalme alternativo y contienen 1281 aminoácidos.

Importancia clínica

Ciertas variantes del gen están asociadas con el efecto protector del café sobre la enfermedad de Parkinson.

Las mutaciones en el gen GRIN2A están asociadas a la epilepsia refractaria.

La secuenciación del exoma/genoma completo ha llevado al descubrimiento de una cercana asociación entre ciertas mutaciones en el gen GRIN2A y una amplia variedad de enfermedades neurológicas, incluyendo epilepsia, discapacidad intelectual, trastornos del espectro autista, retraso del desarrollo y esquizofrenia. Estas enfermedades asociadas a GRIN2A se suelen agrupar como "trastornos relacionados con GRIN2A".

Interacciones

Se ha demostrado que la proteína GRIN2A interactúa con:

Referencias

↑ «Diseases that are genetically associated with GRIN2A view/edit references on wikidata».
↑ «Drugs that physically interact with Glutamate ionotropic receptor NMDA type subunit 2A view/edit references on wikidata».
↑ «Human PubMed Reference:».
↑ «Mouse PubMed Reference:».
↑ Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (February 1998). «Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels». Genomics 47 (3): 423-425. PMID 9480759. doi:10.1006/geno.1997.5132.
↑ Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, Ahmed A, Grundy P, Vajramani G, Bulters D, Altafaj X, Deinhardt K, Vargas-Caballero M (July 2019). «A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain». Molecular Brain 12 (1). PMC 6610962. PMID 31272478. doi:10.1186/s13041-019-0485-9.
↑ Herbrechter R, Hube N, Buchholz R, Reiner A (July 2021). «Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data». Cellular and Molecular Life Sciences 78 (14): 5605-5630. PMC 8257547. PMID 34100982. doi:10.1007/s00018-021-03865-z.
↑ Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H (August 2011). «Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee». PLOS Genetics 7 (8). PMC 3158052. PMID 21876681. doi:10.1371/journal.pgen.1002237.
↑ Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). «Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population». PLOS ONE 9 (6). Bibcode:2014PLoSO...999294Y. PMC 4051678. PMID 24915238. doi:10.1371/journal.pone.0099294.
↑ Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, Bulman D, Boycott KM, Dyment DA (July 2014). «Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation». Epilepsia 55 (7): e75-e79. PMID 24903190. doi:10.1111/epi.12663.
↑ Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). «Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases». Molecular Pharmacology 88 (1): 203-217. PMC 4468639. PMID 25904555. doi:10.1124/mol.115.097998.
↑ Ebrahim AK, Makhlooq JJ, Busehail MY (July 2025). «Landau-Kleffner Syndrome Can Herald the Diagnosis of GRIN2A Gene Mutation». Case Reports in Pediatrics 2025. PMC 12301084. PMID 40727434. doi:10.1155/crpe/8869587.
↑ Xu C, Wang ML, Ling WH, Tang JH (June 2025). «Neurodevelopmental disorder due to a frameshift mutation in the GRIN2A gene: a case report». Translational Pediatrics 14 (6): 1353-1361. PMC 12268631. PMID 40688221. doi:10.21037/tp-2025-93.
↑ Tarabeux J, Kebir O, Gauthier J, Hamdan FF, Xiong L, Piton A, Spiegelman D, Henrion É, Millet B, Fathalli F, Joober R, Rapoport JL, DeLisi LE, Fombonne É, Mottron L, Forget-Dubois N, Boivin M, Michaud JL, Drapeau P, Lafrenière RG, Rouleau GA, Krebs MO (November 2011). «Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia». Translational Psychiatry 1 (11): e55. PMC 3309470. PMID 22833210. doi:10.1038/tp.2011.52.
↑ Strehlow, Vincent; Myers, Kenneth A.; Morgan, Angela T.; Scheffer, Ingrid E.; Lemke, Johannes R. (4 de julio de 2024). GRIN2A-Related Disorders (en inglés). University of Washington, Seattle. Consultado el 13 de octubre de 2026.
↑ Gardoni F, Mauceri D, Fiorentini C, Bellone C, Missale C, Cattabeni F, Di Luca M (November 2003). «CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction». The Journal of Biological Chemistry 278 (45): 44745-44752. PMID 12933808. doi:10.1074/jbc.M303576200.
1 2 Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). «Binding of neuroligins to PSD-95». Science 277 (5331): 1511-1515. PMID 9278515. doi:10.1126/science.277.5331.1511.
1 2 Lim IA, Hall DD, Hell JW (June 2002). «Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102». The Journal of Biological Chemistry 277 (24): 21697-21711. PMID 11937501. doi:10.1074/jbc.M112339200.
1 2 Hou XY, Zhang GY, Yan JZ, Chen M, Liu Y (November 2002). «Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia». Brain Research 955 (1–2): 123-132. PMID 12419528. doi:10.1016/s0006-8993(02)03376-0.
↑ Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (June 1997). «DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95». Genes to Cells 2 (6): 415-424. PMID 9286858. doi:10.1046/j.1365-2443.1997.1310329.x.
↑ Sans N, Petralia RS, Wang YX, Blahos J, Hell JW, Wenthold RJ (February 2000). «A developmental change in NMDA receptor-associated proteins at hippocampal synapses». The Journal of Neuroscience 20 (3): 1260-1271. PMC 6774158. PMID 10648730. doi:10.1523/JNEUROSCI.20-03-01260.2000.
1 2 Ma J, Zhang GY (September 2003). «Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia». Neuroscience Letters 348 (3): 185-189. PMID 12932824. doi:10.1016/s0304-3940(03)00784-5.
↑ Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T (January 1999). «PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A». Proceedings of the National Academy of Sciences of the United States of America 96 (2): 435-440. Bibcode:1999PNAS...96..435T. PMC 15154. PMID 9892651. doi:10.1073/pnas.96.2.435.
1 2 Takagi N, Cheung HH, Bissoon N, Teves L, Wallace MC, Gurd JW (August 1999). «The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains». Journal of Cerebral Blood Flow and Metabolism 19 (8): 880-888. PMID 10458595. doi:10.1097/00004647-199908000-00007.
↑ Kurschner C, Yuzaki M (September 1999). «Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein». The Journal of Neuroscience 19 (18): 7770-7780. PMC 6782450. PMID 10479680. doi:10.1523/JNEUROSCI.19-18-07770.1999.
↑ Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (April 2003). «Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102». The Journal of Biological Chemistry 278 (17): 15040-15048. PMID 12576483. doi:10.1074/jbc.M212825200.
↑ Liu Y, Zhang G, Gao C, Hou X (August 2001). «NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion». Brain Research 909 (1–2): 51-58. PMID 11478920. doi:10.1016/s0006-8993(01)02619-1.

[1] «Diseases that are genetically associated with GRIN2A view/edit references on wikidata».

[2] «Drugs that physically interact with Glutamate ionotropic receptor NMDA type subunit 2A view/edit references on wikidata».

[3] «Human PubMed Reference:».

[4] «Mouse PubMed Reference:».

[Kalsi_1998-5] Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (February 1998). «Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels». Genomics 47 (3): 423-425. PMID 9480759. doi:10.1006/geno.1997.5132.

[6] Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, Ahmed A, Grundy P, Vajramani G, Bulters D, Altafaj X, Deinhardt K, Vargas-Caballero M (July 2019). «A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain». Molecular Brain 12 (1). PMC 6610962. PMID 31272478. doi:10.1186/s13041-019-0485-9.

[7] Herbrechter R, Hube N, Buchholz R, Reiner A (July 2021). «Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data». Cellular and Molecular Life Sciences 78 (14): 5605-5630. PMC 8257547. PMID 34100982. doi:10.1007/s00018-021-03865-z.

[8] Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H (August 2011). «Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee». PLOS Genetics 7 (8). PMC 3158052. PMID 21876681. doi:10.1371/journal.pgen.1002237.

[9] Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). «Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population». PLOS ONE 9 (6). Bibcode:2014PLoSO...999294Y. PMC 4051678. PMID 24915238. doi:10.1371/journal.pone.0099294.

[10] Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, Bulman D, Boycott KM, Dyment DA (July 2014). «Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation». Epilepsia 55 (7): e75-e79. PMID 24903190. doi:10.1111/epi.12663.

[Yuan_2015-11] Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). «Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases». Molecular Pharmacology 88 (1): 203-217. PMC 4468639. PMID 25904555. doi:10.1124/mol.115.097998.

[12] Ebrahim AK, Makhlooq JJ, Busehail MY (July 2025). «Landau-Kleffner Syndrome Can Herald the Diagnosis of GRIN2A Gene Mutation». Case Reports in Pediatrics 2025. PMC 12301084. PMID 40727434. doi:10.1155/crpe/8869587.

[13] Xu C, Wang ML, Ling WH, Tang JH (June 2025). «Neurodevelopmental disorder due to a frameshift mutation in the GRIN2A gene: a case report». Translational Pediatrics 14 (6): 1353-1361. PMC 12268631. PMID 40688221. doi:10.21037/tp-2025-93.

[14] Tarabeux J, Kebir O, Gauthier J, Hamdan FF, Xiong L, Piton A, Spiegelman D, Henrion É, Millet B, Fathalli F, Joober R, Rapoport JL, DeLisi LE, Fombonne É, Mottron L, Forget-Dubois N, Boivin M, Michaud JL, Drapeau P, Lafrenière RG, Rouleau GA, Krebs MO (November 2011). «Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia». Translational Psychiatry 1 (11): e55. PMC 3309470. PMID 22833210. doi:10.1038/tp.2011.52.

[15] Strehlow, Vincent; Myers, Kenneth A.; Morgan, Angela T.; Scheffer, Ingrid E.; Lemke, Johannes R. (4 de julio de 2024). GRIN2A-Related Disorders (en inglés). University of Washington, Seattle. Consultado el 13 de octubre de 2026.

[Gardoni_2003-16] Gardoni F, Mauceri D, Fiorentini C, Bellone C, Missale C, Cattabeni F, Di Luca M (November 2003). «CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction». The Journal of Biological Chemistry 278 (45): 44745-44752. PMID 12933808. doi:10.1074/jbc.M303576200.

[pmid9278515-17] 1 2 Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). «Binding of neuroligins to PSD-95». Science 277 (5331): 1511-1515. PMID 9278515. doi:10.1126/science.277.5331.1511.

[Lim_2002-18] 1 2 Lim IA, Hall DD, Hell JW (June 2002). «Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102». The Journal of Biological Chemistry 277 (24): 21697-21711. PMID 11937501. doi:10.1074/jbc.M112339200.

[Hou_2002-19] 1 2 Hou XY, Zhang GY, Yan JZ, Chen M, Liu Y (November 2002). «Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia». Brain Research 955 (1–2): 123-132. PMID 12419528. doi:10.1016/s0006-8993(02)03376-0.

[pmid9286858-20] Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (June 1997). «DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95». Genes to Cells 2 (6): 415-424. PMID 9286858. doi:10.1046/j.1365-2443.1997.1310329.x.

[Sans_2000-21] Sans N, Petralia RS, Wang YX, Blahos J, Hell JW, Wenthold RJ (February 2000). «A developmental change in NMDA receptor-associated proteins at hippocampal synapses». The Journal of Neuroscience 20 (3): 1260-1271. PMC 6774158. PMID 10648730. doi:10.1523/JNEUROSCI.20-03-01260.2000.

[Ma_2003-22] 1 2 Ma J, Zhang GY (September 2003). «Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia». Neuroscience Letters 348 (3): 185-189. PMID 12932824. doi:10.1016/s0304-3940(03)00784-5.

[Tezuka_1999-23] Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T (January 1999). «PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A». Proceedings of the National Academy of Sciences of the United States of America 96 (2): 435-440. Bibcode:1999PNAS...96..435T. PMC 15154. PMID 9892651. doi:10.1073/pnas.96.2.435.

[Takagi_1999-24] 1 2 Takagi N, Cheung HH, Bissoon N, Teves L, Wallace MC, Gurd JW (August 1999). «The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains». Journal of Cerebral Blood Flow and Metabolism 19 (8): 880-888. PMID 10458595. doi:10.1097/00004647-199908000-00007.

[Kurschner_1999-25] Kurschner C, Yuzaki M (September 1999). «Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein». The Journal of Neuroscience 19 (18): 7770-7780. PMC 6782450. PMID 10479680. doi:10.1523/JNEUROSCI.19-18-07770.1999.

[Seabold_2003-26] Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (April 2003). «Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102». The Journal of Biological Chemistry 278 (17): 15040-15048. PMID 12576483. doi:10.1074/jbc.M212825200.

[Liu_2001-27] Liu Y, Zhang G, Gao C, Hou X (August 2001). «NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion». Brain Research 909 (1–2): 51-58. PMID 11478920. doi:10.1016/s0006-8993(01)02619-1.