GRIA1

glutamate ionotropic receptor AMPA type subunit 1, the group of Glutamate ionotropic receptor AMPA type subunits

Basic information

Region (hg38): 5:153489615-153813869

Previous symbols: [ "GLUR1" ]

Links

ENSG00000155511 ∙ NCBI:2890 ∙ OMIM:138248 ∙ HGNC:4571 ∙ Uniprot:P42261 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 76 (Limited), mode of inheritance: AR
• intellectual developmental disorder, autosomal dominant 67 (Strong), mode of inheritance: AD
• intellectual developmental disorder, autosomal recessive 76 (Limited), mode of inheritance: Unknown
• neurodevelopmental disorder (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 67; Intellectual developmental disorder, autosomal recessive 76	AD/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	23033978; 28628100; 35675825

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRIA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRIA1 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	93	14	1	112
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			3	3	1	7
non coding			1	2	2	5
Total	0	4	98	26	9

Variants in GRIA1

This is a list of pathogenic ClinVar variants found in the GRIA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-153490969-C-A			Benign (Dec 31, 2019)
5-153491305-G-T			Likely benign (Apr 01, 2024)
5-153492228-T-TC		not specified • GRIA1-related disorder	Benign (Feb 16, 2015)
5-153492244-G-A		GRIA1-related disorder	Likely benign (Jun 12, 2019)
5-153492275-G-T		Intellectual developmental disorder, autosomal dominant 67	Benign (Mar 25, 2024)
5-153492309-G-A		Intellectual developmental disorder, autosomal dominant 67	Uncertain significance (-)
5-153493966-G-A		not specified	Uncertain significance (May 17, 2024)
5-153493974-A-T		Inborn genetic diseases	Uncertain significance (Jun 03, 2024)
5-153493985-C-T		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
5-153493999-C-T		Inborn genetic diseases	Uncertain significance (Aug 14, 2024)
5-153494002-C-T		Intellectual developmental disorder, autosomal dominant 67	Uncertain significance (Feb 23, 2023)
5-153494041-G-A		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
5-153494055-G-A		Intellectual developmental disorder, autosomal dominant 67	Uncertain significance (Mar 08, 2024)
5-153646947-A-G		GRIA1-related disorder	Likely benign (Sep 10, 2019)
5-153646951-G-C			Uncertain significance (Dec 20, 2024)
5-153646955-A-C			Uncertain significance (Jul 11, 2022)
5-153646956-T-C			Likely benign (Dec 31, 2019)
5-153646962-C-G		GRIA1-related disorder	Uncertain significance (Sep 19, 2023)
5-153646976-A-C		Intellectual developmental disorder, autosomal dominant 67	Uncertain significance (Dec 21, 2023)
5-153646978-C-T		Inborn genetic diseases	Likely benign (Jun 30, 2023)
5-153646979-G-A		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
5-153647039-C-T		not specified	Uncertain significance (Mar 28, 2024)
5-153647048-C-T		Intellectual developmental disorder, autosomal dominant 67	Uncertain significance (Aug 29, 2023)
5-153647053-G-T		Inborn genetic diseases	Uncertain significance (May 15, 2024)
5-153647084-G-A		Inborn genetic diseases	Likely benign (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRIA1	protein_coding	protein_coding	ENST00000518783	16	324255

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00131	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.60	302	537	0.563	0.0000320	6012
Missense in Polyphen		114	275.91	0.41317		3054
Synonymous	-0.494	220	211	1.04	0.0000136	1752
Loss of Function	5.45	6	45.7	0.131	0.00000234	527

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ionotropic glutamate receptor. 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. {ECO:0000269|PubMed:20805473, ECO:0000269|PubMed:21172611}.
• 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);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Amyotrophic lateral sclerosis (ALS);Common Pathways Underlying Drug Addiction;MECP2 and Associated Rett Syndrome;Phosphodiesterases in neuronal function;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Activation of AMPA receptors;Neuronal System;Synaptic adhesion-like molecules;Cargo concentration in the ER;BDNF;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;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;Protein-protein interactions at synapses;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.293

Intolerance Scores

• loftool: 0.0577
• rvis_EVS: -1.2
• rvis_percentile_EVS: 5.79

Haploinsufficiency Scores

• pHI: 0.399
• hipred: Y
• hipred_score: 0.853
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.681

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gria1
• Phenotype: normal phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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; homeostasis/metabolism phenotype

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;signal transduction;chemical synaptic transmission;long-term memory;receptor internalization;ion transmembrane transport;ionotropic glutamate receptor signaling pathway;COPII vesicle coating;regulation of postsynaptic membrane potential;long-term synaptic depression;regulation of postsynaptic cytosolic calcium ion concentration
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;plasma membrane;synaptic vesicle;cell surface;ER to Golgi transport vesicle membrane;postsynaptic density;cell junction;dendrite;endocytic vesicle membrane;early endosome membrane;AMPA glutamate receptor complex;dendritic spine membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;neuronal cell body;dendritic spine;axonal spine;neuron spine;recycling endosome;recycling endosome membrane;synaptic membrane;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: amyloid-beta binding;AMPA glutamate receptor activity;protein binding;glutamate receptor activity;PDZ domain binding;neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential