GRIN2A

Protein identityUniProt · HPA

UniProt accession

Q12879

Gene

GRIN2A

Ensembl

ENSG00000183454

Chromosome

16

Canonical length

1464 aa

Protein class

Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, RAS pathway related proteins, Transporters

Subcellular location

Endoplasmic reticulum,Vesicles

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1464 residues, UniProt reviewed canonical sequence.

>Q12879|GRIN2A
     1  MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE LRTLWGPEQA
    61  AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF GDDTDQEAVA QMLDFISSHT
   121  FVPILGIHGG ASMIMADKDP TSTFFQFGAS IQQQATVMLK IMQDYDWHVF SLVTTIFPGY
   181  REFISFVKTT VDNSFVGWDM QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL
   241  SEARSLGLTG YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT
   301  TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF TEEGYQVHPR
   361  LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW PRYKSFSDCE PDDNHLSIVT LEEAPFVIVE
   421  DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFC IDILKKLSRT VKFTYDLYLV
   481  TNGKHGKKVN NVWNGMIGEV VYQRAVMAVG SLTINEERSE VVDFSVPFVE TGISVMVSRS
   541  NGTVSPSAFL EPFSASVWVM MFVMLLIVSA IAVFVFEYFS PVGYNRNLAK GKAPHGPSFT
   601  IGKAIWLLWG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEFVD
   661  QVTGLSDKKF QRPHDYSPPF RFGTVPNGST ERNIRNNYPY MHQYMTKFNQ KGVEDALVSL
   721  KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI GSGYIFATTG YGIALQKGSP WKRQIDLALL
   781  QFVGDGEMEE LETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL
   841  FYWKLRFCFT GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTGS QSNMLKLLRS
   901  AKNISSMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ GKESIFGDNM
   961  NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV STESKANSRP RQLWKKSVDS
  1021  IRQDSLSQNP VSQRDEATAE NRTHSLKSPR YLPEEMAHSD ISETSNRATC HREPDNSKNH
  1081  KTKDNFKRSV ASKYPKDCSE VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT
  1141  LPENVDFPDP YQDPSENFRK GDSTLPMNRN PLHNEEGLSN NDQYKLYSKH FTLKDKGSPH
  1201  SETSERYRQN STHCRSCLSN MPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP
  1261  ATGEQVYQQD WAQNNALQLQ KNKLRISRQH SYDNIVDKPR ELDLSRPSRS ISLKDRERLL
  1321  EGNFYGSLFS VPSSKLSGKK SSLFPQGLED SKRSKSLLPD HTSDNPFLHS HRDDQRLVIG
  1381  RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHN DVYISEHVMP YAANKNNMYS
  1441  TPRVLNSCSN RRVYKKMPSI ESDV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIN2A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

3

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIN2A.

Disease | AllUniProt

Conditions GRIN2A is implicated in, by any mechanism.

• Epilepsy, focal, with speech disorder and with or without impaired intellectual development (FESD) MIM:245570

Disease | GeneticClinVar

297 pathogenic / likely-pathogenic of 2,393 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Landau-Kleffner syndrome
• Inborn genetic diseases
• Self-limited epilepsy with centrotemporal spikes
• Seizure
• Intellectual disability

Disease | ImmuneIEDB

Conditions an epitope on GRIN2A was assayed in.

• systemic lupus erythematosus B cell
• myasthenia gravis B cell
• autoimmune polyendocrine syndrome B cell
• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell
• epilepsy B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against GRIN2A are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 4

ReferencesPubMed · IEDB

Publications for GRIN2A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

2.83

DepMap mean gene effect

-0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• calcium ion transmembrane import into cytosol
• calcium ion transmembrane transport
• chemical synaptic transmission
• directional locomotion
• dopamine metabolic process
• excitatory chemical synaptic transmission
• excitatory postsynaptic potential
• glutamate receptor signaling pathway
• ionotropic glutamate receptor signaling pathway
• learning or memory
• long-term synaptic potentiation
• memory
• monoatomic cation transmembrane transport
• negative regulation of protein catabolic process
• neurogenesis
• positive regulation of apoptotic process
• positive regulation of excitatory postsynaptic potential
• positive regulation of synaptic transmission, glutamatergic
• protein catabolic process
• protein localization to postsynaptic membrane
• regulation of monoatomic cation transmembrane transport
• regulation of neuronal synaptic plasticity
• regulation of synaptic plasticity
• response to amphetamine
• response to ethanol
• response to wounding
• response to xenobiotic stimulus
• sensory perception of pain
• serotonin metabolic process
• sleep
• sodium ion transmembrane transport
• startle response
• synaptic transmission, glutamatergic
• visual learning

Molecular functions

• amyloid-beta binding
• glutamate-gated calcium ion channel activity
• NMDA glutamate receptor activity
• transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
• zinc ion binding

Cellular components

• cell surface
• cytoplasmic vesicle membrane
• dendritic spine
• endoplasmic reticulum membrane
• glutamatergic synapse
• NMDA selective glutamate receptor complex
• plasma membrane
• postsynaptic density
• postsynaptic density membrane
• postsynaptic membrane
• presynaptic membrane
• synaptic membrane
• synaptic vesicle

Protein domainsUniProt · Pfam · InterPro

• Ionotropic glutamate receptor, C-terminal
• Ionotropic glutamate receptor, metazoa
• Receptor, ligand binding region
• Ionotropic glutamate receptor
• Glutamate [NMDA] receptor, epsilon subunit, C-terminal
• Ionotropic glutamate receptor, L-glutamate and glycine-binding domain
• Periplasmic binding protein-like I
• Ligand-gated ion channel
• Receptor family ligand binding region
• N-methyl D-aspartate receptor 2B3 C-terminus
• Ligated ion channel L-glutamate- and glycine-binding site

KeywordsUniProt

• Calcium
• Cell membrane
• Cell projection
• Chromosomal rearrangement
• Cytoplasmic vesicle
• Disulfide bond
• Epilepsy
• Glycoprotein
• Ion channel
• Ion transport
• Ligand-gated ion channel
• Magnesium
• Membrane
• Metal-binding
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport
• Zinc

InteractionsUniProt · HPA

Protein binding partners of GRIN2A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AIP1
• ARC
• DLG4
• HIP1
• LRFN2
• NETO1
• RPH3A
• SNX27
• SORCS2
• IL16
• PATJ