GRIN2D (glutamate ionotropic receptor NMDA type subunit 2D)

Gene

• Entrez ID: 2906
• Gene name: Glutamate ionotropic receptor NMDA type subunit 2D
• Gene symbol: GRIN2D
• Synonyms (NCBI Gene): DEE46, EB11, EIEE46, GluN2D, NMDAR2D, NR2D
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certai

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs771799381	G>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs886040861	G>A	Pathogenic	Missense variant, coding sequence variant
rs1569064110	G>A	Pathogenic	Coding sequence variant, missense variant
rs1569065861	G>C	Pathogenic	Coding sequence variant, missense variant
rs1569065866	A>C	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017316	hsa-miR-335-5p	Microarray	18185580
MIRT570165	hsa-miR-4779	PAR-CLIP	20371350
MIRT570166	hsa-miR-6732-5p	PAR-CLIP	20371350
MIRT490929	hsa-miR-6804-5p	PAR-CLIP	20371350
MIRT490927	hsa-miR-7-5p	PAR-CLIP	20371350
MIRT490926	hsa-miR-6077	PAR-CLIP	20371350
MIRT570164	hsa-miR-765	PAR-CLIP	20371350
MIRT570163	hsa-miR-6752-5p	PAR-CLIP	20371350
MIRT570162	hsa-miR-6842-5p	PAR-CLIP	20371350
MIRT570161	hsa-miR-7110-5p	PAR-CLIP	20371350
MIRT570160	hsa-miR-6747-5p	PAR-CLIP	20371350
MIRT490925	hsa-miR-363-5p	PAR-CLIP	20371350
MIRT490923	hsa-miR-6745	PAR-CLIP	20371350
MIRT490924	hsa-miR-3190-3p	PAR-CLIP	20371350
MIRT490931	hsa-miR-4670-5p	PAR-CLIP	23592263
MIRT490929	hsa-miR-6804-5p	PAR-CLIP	23592263
MIRT490928	hsa-miR-6124	PAR-CLIP	23592263
MIRT490927	hsa-miR-7-5p	PAR-CLIP	23592263
MIRT490926	hsa-miR-6077	PAR-CLIP	23592263
MIRT490925	hsa-miR-363-5p	PAR-CLIP	23592263
MIRT490923	hsa-miR-6745	PAR-CLIP	23592263
MIRT490924	hsa-miR-3190-3p	PAR-CLIP	23592263
MIRT490924	hsa-miR-3190-3p	PAR-CLIP	26701625
MIRT490925	hsa-miR-363-5p	PAR-CLIP	26701625
MIRT490931	hsa-miR-4670-5p	PAR-CLIP	26701625
MIRT490926	hsa-miR-6077	PAR-CLIP	26701625
MIRT490928	hsa-miR-6124	PAR-CLIP	26701625
MIRT490923	hsa-miR-6745	PAR-CLIP	26701625
MIRT490929	hsa-miR-6804-5p	PAR-CLIP	26701625
MIRT490927	hsa-miR-7-5p	PAR-CLIP	26701625
MIRT570164	hsa-miR-765	PAR-CLIP	26701625
MIRT570165	hsa-miR-4779	PAR-CLIP	20371350
MIRT570166	hsa-miR-6732-5p	PAR-CLIP	20371350
MIRT490929	hsa-miR-6804-5p	PAR-CLIP	20371350
MIRT490927	hsa-miR-7-5p	PAR-CLIP	20371350
MIRT490926	hsa-miR-6077	PAR-CLIP	20371350
MIRT570164	hsa-miR-765	PAR-CLIP	20371350
MIRT570163	hsa-miR-6752-5p	PAR-CLIP	20371350
MIRT570162	hsa-miR-6842-5p	PAR-CLIP	20371350
MIRT570161	hsa-miR-7110-5p	PAR-CLIP	20371350
MIRT570160	hsa-miR-6747-5p	PAR-CLIP	20371350
MIRT490925	hsa-miR-363-5p	PAR-CLIP	20371350
MIRT490923	hsa-miR-6745	PAR-CLIP	20371350
MIRT490924	hsa-miR-3190-3p	PAR-CLIP	20371350
MIRT490931	hsa-miR-4670-5p	PAR-CLIP	23592263
MIRT490929	hsa-miR-6804-5p	PAR-CLIP	23592263
MIRT490928	hsa-miR-6124	PAR-CLIP	23592263
MIRT490927	hsa-miR-7-5p	PAR-CLIP	23592263
MIRT490926	hsa-miR-6077	PAR-CLIP	23592263
MIRT490925	hsa-miR-363-5p	PAR-CLIP	23592263
MIRT490923	hsa-miR-6745	PAR-CLIP	23592263
MIRT490924	hsa-miR-3190-3p	PAR-CLIP	23592263
MIRT1034474	hsa-miR-1468	CLIP-seq
MIRT1034475	hsa-miR-1908	CLIP-seq
MIRT1034476	hsa-miR-2110	CLIP-seq
MIRT1034477	hsa-miR-296-5p	CLIP-seq
MIRT1034478	hsa-miR-3144-5p	CLIP-seq
MIRT1034479	hsa-miR-3150a-3p	CLIP-seq
MIRT1034480	hsa-miR-3151	CLIP-seq
MIRT1034481	hsa-miR-3191	CLIP-seq
MIRT1034482	hsa-miR-3937	CLIP-seq
MIRT1034483	hsa-miR-4436b-5p	CLIP-seq
MIRT1034484	hsa-miR-4508	CLIP-seq
MIRT1034485	hsa-miR-4532	CLIP-seq
MIRT1034486	hsa-miR-4648	CLIP-seq
MIRT1034487	hsa-miR-4652-5p	CLIP-seq
MIRT1034488	hsa-miR-615-5p	CLIP-seq
MIRT1034489	hsa-miR-663	CLIP-seq
MIRT1034490	hsa-miR-744	CLIP-seq
MIRT2239273	hsa-miR-141	CLIP-seq
MIRT2239274	hsa-miR-147	CLIP-seq
MIRT1034475	hsa-miR-1908	CLIP-seq
MIRT2239275	hsa-miR-200a	CLIP-seq
MIRT2239276	hsa-miR-3911	CLIP-seq
MIRT1034488	hsa-miR-615-5p	CLIP-seq
MIRT2239277	hsa-miR-644	CLIP-seq
MIRT1034489	hsa-miR-663	CLIP-seq
MIRT2450788	hsa-miR-3922-5p	CLIP-seq
MIRT2450789	hsa-miR-4313	CLIP-seq
MIRT2450790	hsa-miR-4655-3p	CLIP-seq
MIRT2543111	hsa-miR-1270	CLIP-seq
MIRT2543112	hsa-miR-1285	CLIP-seq
MIRT2543113	hsa-miR-2467-3p	CLIP-seq
MIRT2543114	hsa-miR-3135b	CLIP-seq
MIRT2543115	hsa-miR-3187-5p	CLIP-seq
MIRT2543116	hsa-miR-3188	CLIP-seq
MIRT2543117	hsa-miR-3652	CLIP-seq
MIRT2543118	hsa-miR-378g	CLIP-seq
MIRT2450788	hsa-miR-3922-5p	CLIP-seq
MIRT2450789	hsa-miR-4313	CLIP-seq
MIRT2543119	hsa-miR-4430	CLIP-seq
MIRT2543120	hsa-miR-4486	CLIP-seq
MIRT2450790	hsa-miR-4655-3p	CLIP-seq
MIRT2543121	hsa-miR-4683	CLIP-seq
MIRT2543122	hsa-miR-4695-5p	CLIP-seq
MIRT2543123	hsa-miR-612	CLIP-seq
MIRT2543124	hsa-miR-620	CLIP-seq
MIRT2450788	hsa-miR-3922-5p	CLIP-seq
MIRT2450789	hsa-miR-4313	CLIP-seq
MIRT2450790	hsa-miR-4655-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001964	Process	Startle response	IEA
GO:0004970	Function	Glutamate-gated receptor activity	IDA	27616483
GO:0004970	Function	Glutamate-gated receptor activity	IEA
GO:0004972	Function	NMDA glutamate receptor activity	IBA
GO:0004972	Function	NMDA glutamate receptor activity	IDA	9489750, 26875626, 26919761
GO:0004972	Function	NMDA glutamate receptor activity	IEA
GO:0004972	Function	NMDA glutamate receptor activity	ISS
GO:0004972	Function	NMDA glutamate receptor activity	TAS	17526495
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005261	Function	Monoatomic cation channel activity	IEA
GO:0005515	Function	Protein binding	IPI	11937501
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	26875626, 26919761
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	NAS	36959261
GO:0005886	Component	Plasma membrane	TAS
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0007420	Process	Brain development	NAS	17526495
GO:0008344	Process	Adult locomotory behavior	IEA
GO:0015276	Function	Ligand-gated monoatomic ion channel activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016595	Function	Glutamate binding	IEA
GO:0017146	Component	NMDA selective glutamate receptor complex	IBA
GO:0017146	Component	NMDA selective glutamate receptor complex	IDA	26875626, 26919761, 36309015
GO:0017146	Component	NMDA selective glutamate receptor complex	IEA
GO:0017146	Component	NMDA selective glutamate receptor complex	TAS	17526495
GO:0019722	Process	Calcium-mediated signaling	IEA
GO:0022843	Function	Voltage-gated monoatomic cation channel activity	IEA
GO:0022849	Function	Glutamate-gated calcium ion channel activity	IDA	26875626
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0035235	Process	Ionotropic glutamate receptor signaling pathway	IEA
GO:0035235	Process	Ionotropic glutamate receptor signaling pathway	NAS	36959261
GO:0035249	Process	Synaptic transmission, glutamatergic	IBA
GO:0035249	Process	Synaptic transmission, glutamatergic	IEA
GO:0038023	Function	Signaling receptor activity	IEA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0045211	Component	Postsynaptic membrane	ISS
GO:0045211	Component	Postsynaptic membrane	NAS	15317856
GO:0048167	Process	Regulation of synaptic plasticity	IEA
GO:0048167	Process	Regulation of synaptic plasticity	ISS
GO:0048167	Process	Regulation of synaptic plasticity	NAS	17526495
GO:0048168	Process	Regulation of neuronal synaptic plasticity	NAS	15003177
GO:0048787	Component	Presynaptic active zone membrane	IEA
GO:0051930	Process	Regulation of sensory perception of pain	IEA
GO:0051968	Process	Positive regulation of synaptic transmission, glutamatergic	IEA
GO:0051968	Process	Positive regulation of synaptic transmission, glutamatergic	NAS	15003177
GO:0060079	Process	Excitatory postsynaptic potential	IBA
GO:0060291	Process	Long-term synaptic potentiation	IBA
GO:0097553	Process	Calcium ion transmembrane import into cytosol	IDA	26875626
GO:0097553	Process	Calcium ion transmembrane import into cytosol	IEA
GO:0098655	Process	Monoatomic cation transmembrane transport	IDA	9489750, 26875626
GO:0098655	Process	Monoatomic cation transmembrane transport	IDA	9489750, 26875626
GO:0098655	Process	Monoatomic cation transmembrane transport	IEA
GO:0098655	Process	Monoatomic cation transmembrane transport	NAS	36959261
GO:0098686	Component	Hippocampal mossy fiber to CA3 synapse	IEA
GO:0098839	Component	Postsynaptic density membrane	IBA
GO:0098839	Component	Postsynaptic density membrane	IEA
GO:0098976	Process	Excitatory chemical synaptic transmission	NAS	17526495
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099505	Process	Regulation of presynaptic membrane potential	IEA
GO:0099507	Function	Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA
GO:1904062	Process	Regulation of monoatomic cation transmembrane transport	IEA
GO:1904062	Process	Regulation of monoatomic cation transmembrane transport	NAS	15003177
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IEA
GO:1905232	Process	Cellular response to L-glutamate	IEA
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	IEA
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	NAS	36959261

Other IDs

• MIM: 602717
• HGNC: 4588
• e!Ensembl: ENSG00000105464

Protein

• UniProt ID: O15399
• Protein name: Glutamate receptor ionotropic, NMDA 2D (GluN2D) (EB11) (Glutamate [NMDA] receptor subunit epsilon-4) (N-methyl D-aspartate receptor subtype 2D) (NMDAR2D) (NR2D)
• Protein function: Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:26875626, PubMed:27616483, PubMed:28126851,
• PDB: 7YFF, 7YFL, 7YFM, 7YFO, 7YFR, 8E96, 8Y1V, 9D37, 9D38, 9D39, 9D3A, 9D3B, 9D3C
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	83 → 396	Receptor family ligand binding region	Family
  PF10613	Lig_chan-Glu_bd	473 → 569	Ligated ion channel L-glutamate- and glycine-binding site	Domain
  PF00060	Lig_chan	582 → 856	Ligand-gated ion channel	Family

• Sequence:

  MRGAGGPRGPRGPAKMLLLLALACASPFPEEAPGPGGAGGPGGGLGGARPLNVALVFSGP
  AYAAEAARLGPAVAAAVRSPGLDVRPVALVLNGSDPRSLVLQLCDLLSGLRVHGVVFEDD
  SRAPAVAPILDFLSAQTSLPIVAVHGGAALVLTPKEKGSTFLQLGSSTEQQLQVIFEVLE
  EYDWTSFVAVTTRAPGHRAFLSYIEVLTDGSLVGWEHRGALTLDPGAGEAVLSAQLRSVS
  AQIRLLFCAREEAEPVFRAAEEAGLTGSGYVWFMVGPQLAGGGGSGAPGEPPLLPGGAPL
  PAGLFAVRSAGWRDDLARRVAAGVAVVARGAQALLRDYGFLPELGHDCRAQNRTHRGESL
  HRYFMNITWDNRDYSFNEDGFLVNPSLVVISLTRDRTWEVVGSWEQQTLRLKYPLWSRYG
  RFLQPVDDTQHLTVATLEERPFVIVEPADPISGTCIRDSVPCRSQLNRTHSPPPDAPRPE
  KRCCKGFCIDILKRLAHTIGFSYDLYLVTNGKHGKKIDGVWNGMIGEVFYQRADMAIGSL
  TINEERSEIVDFSVPFVETGISVMVARSNGTVSPSAFLEPYSPAVWVMMFVMCLTVVAVT
  VFIFEYLSPVGYNRSLATGKRPGGSTFTIGKSIWLLWALVFNNSVPVENPRGTTSKIMVL
  VWAFFAVIFLASYTANLAAFMIQEEYVDTVSGLSDRKFQRPQEQYPPLKFGTVPNGSTEK
  NIRSNYPDMHSYMVRYNQPRVEEALTQLKAGKLDAFIYDAAVLNYMARKDEGCKLVTIGS
  GKVFATTGYGIALHKGSRWKRPIDLALLQFLGDDEIEMLERLWLSGICHNDKIEVMSSKL
  DIDNMAGVFYMLLVAMGLSLLVFAWEHLVYWRLRHCLGPTHRMDFLLAFSRGMYSCCSAE
  AAPPPAKPPPPPQPLPSPAYPAPRPAPGPAPFVPRERASVDRWRRTKGAGPPGGAGLADG
  FHRYYGPIEPQGLGLGLGEARAAPRGAAGRPLSPPAAQPPQKPPPSYFAIVRDKEPAEPP
  AGAFPGFPSPPAPPAAAATAVGPPLCRLAFEDESPPAPARWPRSDPESQPLLGPGAGGAG
  GTGGAGGGAPAAPPPCRAAPPPCPYLDLEPSPSDSEDSESLGGASLGGLEPWWFADFPYP
  YAERLGPPPGRYWSVDKLGGWRAGSWDYLPPRSGPAAWHCRHCASLELLPPPRHLSCSHD
  GLDGGWWAPPPPPWAAGPLPRRRARCGCPRSHPHRPRASHRTPAAAAPHHHRHRRAAGGW
  DLPPPAPTSRSLEDLSSCPRAAPARRLTGPSRHARRCPHAAHWGPPLPTASHRRHRGGDL
  GTRRGSAHFSSLESEV

• Sequence length: 1336

Pathways

KEGG:

Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Circadian entrainment
Long-term potentiation
Glutamatergic synapse
Alzheimer disease
Amyotrophic lateral sclerosis
Spinocerebellar ataxia
Prion disease
Pathways of neurodegeneration - multiple diseases
Cocaine addiction
Amphetamine addiction
Nicotine addiction
Alcoholism

Reactome:

Unblocking of NMDA receptors, glutamate binding and activation
RAF/MAP kinase cascade
Synaptic adhesion-like molecules
Assembly and cell surface presentation of NMDA receptors

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Developmental and epileptic encephalopathy, 46	Likely pathogenic; Pathogenic	rs1555893359, rs2147452753, rs2147455922, rs901526282, rs2147455888, rs2513690519, rs886040861, rs1569065861, rs1569065866, rs1569064110	RCV005253793 RCV001785273 RCV001785274 RCV001808954 RCV002250038 RCV002466331 RCV000257970 RCV000736015 RCV000736016 RCV000736017

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Developmental disorder	Likely benign	rs1971305781	RCV003764468
Gastric cancer	Uncertain significance	rs1258193242	RCV005920762
GRIN2D-related disorder	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	rs773824115, rs1459290952, rs1448941653, rs773803571, rs369769435, rs1461904559, rs746578868, rs778297666, rs2513690624, rs1319668543, rs1361618111, rs2513693531, rs2516062865, rs776934120, rs2513691157, rs1971341588, rs1160229233, rs2513694261, rs2513675252, rs1317407702, rs2513676721, rs1600967281, rs2516062058, rs2516062080, rs1600967287, rs774133185, rs571334598, rs144676582, rs771799381, rs77992710, rs150885362, rs148340456, rs1015965636	RCV003908879 RCV004752006 RCV003418263 RCV003958630 RCV003916299 RCV004750823 RCV003971304 RCV003943449 RCV003961107 RCV003916509 RCV004750780 RCV003953823 RCV005429100 RCV003391444 RCV003402175 RCV003400299 RCV003412174 RCV003405842 RCV003897071 RCV003921595 RCV003919842 RCV003929731 RCV003902240 RCV003949734 RCV003939333 RCV003969078 RCV003935343 RCV003978186 RCV003935840 RCV003972931 RCV003950585 RCV003923290 RCV003933224
Intellectual disability	Uncertain significance; Likely benign	rs1970669406, rs750359083, rs1970943117, rs1297532606, rs1971324842, rs1386318829, rs1340140743, rs1261712245	RCV001252261 RCV001252262 RCV001252263 RCV001252258 RCV001252264 RCV001252259 RCV001252257 RCV001252260
Melanoma	Uncertain significance	rs2147451651, rs2147455389	RCV005923902 RCV005934636
Ovarian serous cystadenocarcinoma	Uncertain significance	rs766471644	RCV005934957
See cases	Uncertain significance	rs935135704, rs1970766242, rs371691127	RCV002252744 RCV002287822 RCV003128462
Seizure	Uncertain significance	rs2147441538	RCV002275908
Thymoma	Likely benign	rs1249708741	RCV005931568

Associations from Text Mining
Disease Name	Relationship Type	References
Alzheimer Disease	Associate	37794492
Brain Diseases	Associate	27616483, 33397303, 33482465
Breast Neoplasms	Associate	22302350
Coronary Artery Disease	Associate	40147550
Coronary Disease	Associate	40147550
Death Sudden Cardiac	Associate	33397303
Depressive Disorder	Stimulate	26013316
Epilepsy	Associate	33397303, 37095367
Epilepsy Tonic Clonic	Stimulate	26013316
Epileptic Encephalopathy Early Infantile 3	Associate	33397303, 33482465
Keratitis Dendritic	Associate	27616483
Leukemia Lymphoma Adult T Cell	Associate	34446027
Mental Disorders	Associate	33208725
Neoplasms	Associate	20061814, 29672706
Nerve Degeneration	Associate	27616483
Paraparesis Tropical Spastic	Associate	34446027
Schizophrenia	Associate	29317596, 33208725, 8613785
Stomach Neoplasms	Associate	38438090
Triple Negative Breast Neoplasms	Associate	35295962