GRID2

glutamate ionotropic receptor delta type subunit 2, the group of Glutamate ionotropic receptor delta type subunits

Basic information

Region (hg38): 4:92303965-93810157

Links

ENSG00000152208 ∙ NCBI:2895 ∙ OMIM:602368 ∙ HGNC:4576 ∙ Uniprot:O43424 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spinocerebellar ataxia 18 (Supportive), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 18	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23611888; 24078737

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRID2 gene.

• not provided (125 variants)
• Inborn genetic diseases (31 variants)
• Autosomal recessive spinocerebellar ataxia 18 (10 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRID2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	30	9	40
missense	1	2	62	3	3	71
nonsense	1	2				3
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding			1	8	30	39
Total	2	4	65	41	42

Highest pathogenic variant AF is 0.0000131

Variants in GRID2

This is a list of pathogenic ClinVar variants found in the GRID2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-92304340-C-T			Benign (May 12, 2021)
4-92304595-C-T		Autosomal recessive spinocerebellar ataxia 18	Uncertain significance (Oct 12, 2022)
4-92304677-C-T		GRID2-related disorder	Likely benign (Sep 06, 2019)
4-92304696-T-A		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
4-92304709-G-A			Likely pathogenic (Sep 07, 2018)
4-92304718-C-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2022)
4-92304718-C-T			Uncertain significance (Nov 03, 2022)
4-92304731-G-C			Likely benign (Jul 17, 2018)
4-92304740-C-T			Likely benign (Feb 03, 2023)
4-92304743-C-T		GRID2-related disorder	Benign/Likely benign (Aug 30, 2023)
4-92304774-A-T			Likely benign (Dec 07, 2021)
4-92304923-C-G			Benign (Apr 13, 2021)
4-92590120-C-T			Likely benign (May 20, 2023)
4-92590127-C-T			Likely benign (Aug 30, 2023)
4-92590138-T-G		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
4-92590143-A-G		Autosomal recessive spinocerebellar ataxia 18	Uncertain significance (Nov 22, 2023)
4-92590159-G-T		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
4-92590163-G-T		Autosomal recessive spinocerebellar ataxia 18	Uncertain significance (Jan 18, 2018)
4-92590175-C-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
4-92590204-TGAG-T			Uncertain significance (Mar 26, 2022)
4-92590219-G-A			Likely benign (Jan 07, 2024)
4-92590245-C-T		GRID2-related disorder	Benign/Likely benign (Jan 29, 2024)
4-92590246-G-A		GRID2-related disorder	Likely benign (Apr 12, 2022)
4-92590254-A-C		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
4-92590330-G-A			Benign (May 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRID2	protein_coding	protein_coding	ENST00000282020	16	1470158

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000243	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.708	527	575	0.917	0.0000317	6604
Missense in Polyphen		177	234.83	0.75373		2618
Synonymous	-1.07	229	209	1.09	0.0000115	1993
Loss of Function	6.29	4	53.8	0.0744	0.00000322	549

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000278	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. Promotes synaptogenesis and mediates the D-Serine- dependent long term depression signals and AMPA receptor endocytosis of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses through the beta-NRX1-CBLN1-GRID2 triad complex (PubMed:27418511). {ECO:0000269|PubMed:27418511}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 18 (SCAR18) [MIM:616204]: Spinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR18 features include progressive cerebellar atrophy, delayed psychomotor development, severely impaired gait, ocular movement abnormalities, and intellectual disability. {ECO:0000269|PubMed:23611888, ECO:0000269|PubMed:24078737, ECO:0000269|PubMed:25841024, ECO:0000269|PubMed:27418511}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Long-term depression - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.0371
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.4

Haploinsufficiency Scores

• pHI: 0.347
• hipred: Y
• hipred_score: 0.846
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.800

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grid2
• Phenotype: reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;glutamate receptor signaling pathway;regulation of neuron projection development;cerebellar granule cell differentiation;ion transmembrane transport;cellular protein localization;ionotropic glutamate receptor signaling pathway;synaptic transmission, glutamatergic;regulation of neuron apoptotic process;modulation of chemical synaptic transmission;positive regulation of synapse assembly;excitatory postsynaptic potential;prepulse inhibition;regulation of postsynaptic density assembly;positive regulation of long-term synaptic depression;excitatory synapse assembly
• Cellular component: plasma membrane;integral component of plasma membrane;ionotropic glutamate receptor complex;cell junction;dendritic spine;synapse;postsynaptic membrane;parallel fiber to Purkinje cell synapse;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: ionotropic glutamate receptor activity;protein binding;glutamate receptor activity;PDZ domain binding;scaffold protein binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential