Pathway Human Homo sapiens

Assembly and cell surface presentation of NMDA receptors

R-HSA-9609736 in Reactome release 97: under Activation of NMDA receptors and postsynaptic events, with 44 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9609736 (mouse), R-RNO-9609736 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9609736.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2019-03-20
Last updated: 2020-03-16
Events inside: 23, counted from the record

N-methyl-D-aspartate receptors (NMDARs) are tetramers that consist of two GluN1 (GRIN1) subunits and two subunits that belong to either the GluN2 (GRIN2) subfamily (GluN2A, GluN2B, GluN2C and GluN2D) or the GluN3 (GRIN3) subfamily (GluN3A and GluN3B). The GluN2/GluN3 subunits in the NMDA tetramer can either be identical, constituting an NMDA di-heteromer (di-heterotetramer), which consists of two subunit types, GluN1 and one of GluN2s/GluN3s, or they can be two different GluN2/GluN3 proteins, constituting an NMDA tri-heteromer (tri-heterotetramer), which consists of three subunit types, GluN1 and two of GluN2s/GluN3s (Monyer et al. 1992, Wafford et al. 1993, Sheng et al. 1994, Dunah et al. 1998, Perez-Otano et al. 2001, Chatterton et al. 2002, Matsuda et al. 2002, Yamakura et al. 2005, Nilsson et al. 2007, Hansen et al. 2014, Kaiser et al. 2018, Bhattacharya et al. 2018, Bhattacharya and Traynelis 2018).

NMDA tetramers assemble in the endoplasmic reticulum and traffic to the plasma membrane as part of transport vesicles (McIlhinney et al. 1998, Perez-Otano et al. 2001). NMDA receptor subunits undergo N-glycosylation, which impacts their trafficking from the endoplasmic reticulum to the plasma membrane. Trafficking efficiency may vary among different subunits of NMDARs (Lichnereva et al. 2015). Mechanistic details, such as glycosyl transferases involved and the type of sugar side chains added, are not known.

As there are eight splicing isoforms of GluN1, four different GluN2 and two different GluN3 proteins, many different combinations of NMDAR subunits are possible, but only a handful of distinct NMDAR receptors have been experimentally confirmed and functionally studied. The composition of NMDARs affects trafficking, spatial (including synaptic) localization, ligand preference, channel conductivity and downstream signal transmission. Prevalent NMDARs differ at different stages of neuronal development, in different regions of the central nervous system, and at different levels of neuronal activity. For review, please refer to Lau and Zukin 2007, Traynelis et al. 2010, Paoletti et al. 2013, Pérez-Otaño et al. 2016, Iacobucci and Popescu 2017.

Literature Reactome attaches

NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and diseaseNat. Rev. Neurosci., 2013, vol. 14, p. 383-400PubMed 23686171
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disordersNat. Rev. Neurosci., 2007, vol. 8, p. 413-26PubMed 17514195
Emerging roles of GluN3-containing NMDA receptors in the CNSNat. Rev. Neurosci., 2016, vol. 17, p. 623-35PubMed 27558536
NMDA receptors: linking physiological output to biophysical operationNat. Rev. Neurosci., 2017, vol. 18, p. 236-249PubMed 28303017
Assembly intracellular targeting and cell surface expression of the human N-methyl-D-aspartate receptor subunits NR1a and NR2A in transfected cellsNeuropharmacology, 1998, vol. 37, p. 1355-67PubMed 9849671
Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptorsJ. Neurosci., 2001, vol. 21, p. 1228-37PubMed 11160393
Two N-glycosylation Sites in the GluN1 Subunit Are Essential for Releasing N-methyl-d-aspartate (NMDA) Receptors from the Endoplasmic ReticulumJ. Biol. Chem., 2015, vol. 290, p. 18379-90PubMed 26045554
Changing subunit composition of heteromeric NMDA receptors during development of rat cortexNature, 1994, vol. 368, p. 144-7PubMed 8139656
Heteromeric NMDA receptors: molecular and functional distinction of subtypesScience, 1992, vol. 256, p. 1217-21PubMed 1350383
Subunit composition of N-methyl-D-aspartate receptors in the central nervous system that contain the NR2D subunitMol. Pharmacol., 1998, vol. 53, p. 429-37PubMed 9495808
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunitsNature, 2002, vol. 415, p. 793-8PubMed 11823786
Preferential co-assembly of recombinant NMDA receptors composed of three different subunitsNeuroreport, 1993, vol. 4, p. 1347-9PubMed 7903167
Analysis of NR3A receptor subunits in human native NMDA receptorsBrain Res., 2007, vol. 1186, p. 102-12PubMed 17997397
The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-D-aspartate receptorsAnesth. Analg., 2005, vol. 100, p. 1687-92PubMed 15920196
Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeabilityBrain Res. Mol. Brain Res., 2002, vol. 100, p. 43-52PubMed 12008020
Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptorsNeuron, 2014, vol. 81, p. 1084-1096PubMed 24607230
The Bioactive Protein-Ligand Conformation of GluN2C-Selective Positive Allosteric Modulators Bound to the NMDA ReceptorMol. Pharmacol., 2018, vol. 93, p. 141-156PubMed 29242355
Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule CellsNeuron, 2018, vol. 99, p. 315-328.e5PubMed 30056832
Unique Biology and Single-Channel Properties of GluN2A- and GluN2C-Containing Triheteromeric N-Methyl-D-Aspartate ReceptorsJ Exp Neurosci, 2018, vol. 12, p. 1179069518810423PubMed 30479490
Glutamate receptor ion channels: structure, regulation, and functionPharmacol. Rev., 2010, vol. 62, p. 405-96PubMed 20716669

Reactome's record lists 9 orthologous events, R-MMU-9609736 (Mus musculus), R-RNO-9609736 (Rattus norvegicus) among the species this site serves, and 7 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Assembly and cell surface presentation of NMDA receptors". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9609736 with StableID: R-HSA-9609736.5 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 44 genes in this human pathway; showing 1 to 44, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneACTN2	AuthorityHGNC:164	Mapping file id88 NCBI file	EvidenceIEA
GeneAPBA1	AuthorityHGNC:578	Mapping file id320 NCBI file	EvidenceIEA
GeneCAMK2A	AuthorityHGNC:1460	Mapping file id815 NCBI file	EvidenceIEA
GeneCAMK2B	AuthorityHGNC:1461	Mapping file id816 NCBI file	EvidenceIEA
GeneCAMK2D	AuthorityHGNC:1462	Mapping file id817 NCBI file	EvidenceIEA
GeneCAMK2G	AuthorityHGNC:1463	Mapping file id818 NCBI file	EvidenceIEA
GeneCASK	AuthorityHGNC:1497	Mapping file id8573 NCBI file	EvidenceIEA
GeneDLG1	AuthorityHGNC:2900	Mapping file id1739 NCBI file	EvidenceIEA
GeneDLG2	AuthorityHGNC:2901	Mapping file id1740 NCBI file	EvidenceIEA
GeneDLG3	AuthorityHGNC:2902	Mapping file id1741 NCBI file	EvidenceIEA
GeneDLG4	AuthorityHGNC:2903	Mapping file id1742 NCBI file	EvidenceIEA
GeneGRIN1	AuthorityHGNC:4584	Mapping file id2902 NCBI file	EvidenceIEA, TAS
GeneGRIN2A	AuthorityHGNC:4585	Mapping file id2903 NCBI file	EvidenceIEA, TAS
GeneGRIN2B	AuthorityHGNC:4586	Mapping file id2904 NCBI file	EvidenceIEA, TAS
GeneGRIN2C	AuthorityHGNC:4587	Mapping file id2905 NCBI file	EvidenceIEA, TAS
GeneGRIN2D	AuthorityHGNC:4588	Mapping file id2906 NCBI file	EvidenceIEA, TAS
GeneGRIN3A	AuthorityHGNC:16767	Mapping file id116443 NCBI file	EvidenceIEA, TAS
GeneGRIN3B	AuthorityHGNC:16768	Mapping file id116444 NCBI file	EvidenceIEA
GeneKIF17	AuthorityHGNC:19167	Mapping file id57576 NCBI file	EvidenceIEA
GeneLIN7A	AuthorityHGNC:17787	Mapping file id8825 NCBI file	EvidenceIEA
GeneLIN7B	AuthorityHGNC:17788	Mapping file id64130 NCBI file	EvidenceIEA
GeneLIN7C	AuthorityHGNC:17789	Mapping file id55327 NCBI file	EvidenceIEA
GeneLRRC7	AuthorityHGNC:18531	Mapping file id57554 NCBI file	EvidenceIEA
GeneNBEA	AuthorityHGNC:7648	Mapping file id26960 NCBI file	EvidenceIEA
GeneNEFL	AuthorityHGNC:7739	Mapping file id4747 NCBI file	EvidenceIEA
GeneTUBA1A	AuthorityHGNC:20766	Mapping file id7846 NCBI file	EvidenceIEA
GeneTUBA1B	AuthorityHGNC:18809	Mapping file id10376 NCBI file	EvidenceIEA
GeneTUBA1C	AuthorityHGNC:20768	Mapping file id84790 NCBI file	EvidenceIEA
GeneTUBA3C	AuthorityHGNC:12408	Mapping file id7278 NCBI file	EvidenceIEA
GeneTUBA3D	AuthorityHGNC:24071	Mapping file id113457 NCBI file	EvidenceIEA
GeneTUBA3E	AuthorityHGNC:20765	Mapping file id112714 NCBI file	EvidenceIEA
GeneTUBA4A	AuthorityHGNC:12407	Mapping file id7277 NCBI file	EvidenceIEA
GeneTUBA4B	AuthorityHGNC:18637	Mapping file id80086 NCBI file	EvidenceIEA
GeneTUBA8	AuthorityHGNC:12410	Mapping file id51807 NCBI file	EvidenceIEA
GeneTUBAL3	AuthorityHGNC:23534	Mapping file id79861 NCBI file	EvidenceIEA
GeneTUBB1	AuthorityHGNC:16257	Mapping file id81027 NCBI file	EvidenceIEA
GeneTUBB2A	AuthorityHGNC:12412	Mapping file id7280 NCBI file	EvidenceIEA
GeneTUBB2B	AuthorityHGNC:30829	Mapping file id347733 NCBI file	EvidenceIEA
GeneTUBB3	AuthorityHGNC:20772	Mapping file id10381 NCBI file	EvidenceIEA
GeneTUBB4A	AuthorityHGNC:20774	Mapping file id10382 NCBI file	EvidenceIEA
GeneTUBB4B	AuthorityHGNC:20771	Mapping file id10383 NCBI file	EvidenceIEA
GeneTUBB6	AuthorityHGNC:20776	Mapping file id84617 NCBI file	EvidenceIEA
GeneTUBB8	AuthorityHGNC:20773	Mapping file id347688 NCBI file	EvidenceIEA
GeneTUBB8B	AuthorityHGNC:24983	Mapping file id260334 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Activation of NMDA receptors and postsynaptic eventsR-HSA-44275596 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.