GRIA2

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

Basic information

Region (hg38): 4:157204182-157387146

Previous symbols: [ "GLUR2" ]

Links

ENSG00000120251 ∙ NCBI:2891 ∙ OMIM:138247 ∙ HGNC:4572 ∙ Uniprot:P42262 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with language impairment and behavioral abnormalities (Definitive), mode of inheritance: AD
• neurodevelopmental disorder with language impairment and behavioral abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with language impairment and behavioral abnormalities (Definitive), mode of inheritance: AD
• neurodevelopmental disorder with language impairment and behavioral abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with language impairment and behavioral abnormalities	AD	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	31300657

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRIA2 gene.

• Neurodevelopmental disorder with language impairment and behavioral abnormalities (8 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRIA2 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				10	6	16
missense	4	18	64	5	2	93
nonsense	2	3				5
start loss			1			1
frameshift	2	1				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	2	1	5
non coding			1	3	1	5
Total	8	22	67	18	9

Variants in GRIA2

This is a list of pathogenic ClinVar variants found in the GRIA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-157221055-A-T			Uncertain significance (May 25, 2022)
4-157221056-T-C		Neurodevelopmental disorder with language impairment and behavioral abnormalities	Uncertain significance (Jan 27, 2023)
4-157221065-C-A			Uncertain significance (Sep 28, 2022)
4-157221107-T-G			Uncertain significance (Nov 21, 2022)
4-157221112-T-C			Uncertain significance (Sep 07, 2022)
4-157221668-G-T			Benign (Aug 01, 2024)
4-157221683-G-C		Inborn genetic diseases	Uncertain significance (May 28, 2024)
4-157221688-C-T		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
4-157221704-T-C			Likely benign (Oct 10, 2018)
4-157221718-G-A		Neurodevelopmental disorder with language impairment and behavioral abnormalities	Uncertain significance (Apr 01, 2021)
4-157221720-A-G			Uncertain significance (Feb 17, 2023)
4-157221759-C-G			Uncertain significance (Feb 15, 2024)
4-157303568-G-A			Likely benign (Sep 01, 2023)
4-157303579-AT-A		Neurodevelopmental disorder with language impairment and behavioral abnormalities	Pathogenic (Jan 01, 2020)
4-157303609-C-G			Uncertain significance (Jul 08, 2022)
4-157303611-G-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
4-157303646-C-T			Likely benign (Dec 31, 2019)
4-157303662-C-T		GRIA2-related disorder	Uncertain significance (Apr 03, 2023)
4-157303706-G-A			Benign (Sep 01, 2023)
4-157303712-C-T		not specified	Likely benign (Jan 15, 2024)
4-157303720-A-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
4-157303735-G-A		EBV-positive nodal T- and NK-cell lymphoma	Uncertain significance (Jun 15, 2023)
4-157303758-G-A			Uncertain significance (May 16, 2022)
4-157303777-A-G			Uncertain significance (Jan 04, 2023)
4-157303799-A-G			Likely benign (Jul 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRIA2	protein_coding	protein_coding	ENST00000296526	15	161894

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000835	125699	0	7	125706	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.56	197	477	0.413	0.0000243	5804
Missense in Polyphen		42	229.41	0.18308		2839
Synonymous	0.568	172	182	0.946	0.0000105	1675
Loss of Function	5.33	5	42.5	0.118	0.00000199	535

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000163	0.000161
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P19491, ECO:0000269|PubMed:20614889}.
• Pathway: Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Long-term depression - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);miR-targeted genes in muscle cell - TarBase;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Common Pathways Underlying Drug Addiction;fosb gene expression and drug abuse;Activation of AMPA receptors;Neuronal System;BDNF;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Unblocking of NMDA receptor, glutamate binding and activation;Activation of NMDA receptor and postsynaptic events;N-cadherin signaling events (Consensus)

Recessive Scores

• pRec: 0.258

Intolerance Scores

• loftool: 0.0604
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.88

Haploinsufficiency Scores

• pHI: 0.306
• hipred: Y
• hipred_score: 0.817
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gria2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region 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); normal 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)

Zebrafish Information Network

• Gene name: gria2a
• Affected structure: anterior lateral line neuromast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: signal transduction;chemical synaptic transmission;ion transmembrane transport;ionotropic glutamate receptor signaling pathway;synaptic transmission, glutamatergic
• Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell junction;dendrite;endocytic vesicle membrane;AMPA glutamate receptor complex;dendritic spine;postsynaptic membrane;excitatory synapse;postsynapse;postsynaptic endocytic zone
• Molecular function: amyloid-beta binding;ionotropic glutamate receptor activity;AMPA glutamate receptor activity;protein binding