GRIK2

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

Basic information

Region (hg38): 6:100962701-102081622

Previous symbols: [ "GLUR6" ]

Links

ENSG00000164418 ∙ NCBI:2898 ∙ OMIM:138244 ∙ HGNC:4580 ∙ Uniprot:Q13002 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 6 (Definitive), mode of inheritance: AR
• intellectual disability, autosomal recessive 6 (Limited), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 6 (Strong), mode of inheritance: AR
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Moderate), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures; Intellectual developmental disorder, autosomal recessive 6	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	17120046; 17847003; 25039795; 28180184; 34375587

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRIK2 gene.

• Neurodevelopmental disorder with impaired language and ataxia and with or without seizures (2 variants)
• 6 conditions (1 variants)
• GRIK2-related neurodevelopmental disorder (1 variants)
• not provided (1 variants)
• Intellectual disability;Severe global developmental delay;Gait ataxia (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRIK2 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			4	30	4	38
missense	2	1	82	6	1	92
nonsense		2	2			4
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		2	1			3
splice region			3	6	2	11
non coding				1	3	4
Total	2	5	89	37	8

Variants in GRIK2

This is a list of pathogenic ClinVar variants found in the GRIK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-101399291-T-C			Uncertain significance (Jul 28, 2022)
6-101399309-C-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
6-101399317-A-G			Uncertain significance (Jan 26, 2024)
6-101399332-C-A			Uncertain significance (Apr 19, 2023)
6-101399342-G-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
6-101399377-C-T			Uncertain significance (Oct 01, 2017)
6-101399379-T-C			Likely benign (Dec 11, 2018)
6-101621952-G-T		Inborn genetic diseases	Uncertain significance (Apr 04, 2024)
6-101621983-G-A		not specified	Uncertain significance (Oct 30, 2015)
6-101622038-A-G		Neurodevelopmental disorder with impaired language and ataxia and with or without seizures	Uncertain significance (Dec 07, 2021)
6-101622041-T-C			Likely benign (Dec 08, 2017)
6-101622048-C-A		Developmental disorder	Likely benign (Jan 17, 2022)
6-101622055-T-C		not specified	Uncertain significance (Sep 23, 2015)
6-101622056-A-G			Uncertain significance (Nov 16, 2022)
6-101622058-C-A			Likely benign (Aug 27, 2018)
6-101622072-C-T		GRIK2-related disorder	Uncertain significance (May 28, 2024)
6-101622094-T-C			Uncertain significance (Aug 15, 2020)
6-101622114-A-G		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
6-101622117-G-C			Likely pathogenic (Nov 23, 2022)
6-101626418-G-T			Uncertain significance (Jul 01, 2023)
6-101626444-C-T		GRIK2-related disorder	Likely benign (May 01, 2023)
6-101626451-C-T		Neurodevelopmental disorder with impaired language and ataxia and with or without seizures	Likely pathogenic (Aug 18, 2023)
6-101626457-A-G		Neurodevelopmental disorder with impaired language and ataxia and with or without seizures	Uncertain significance (Dec 19, 2024)
6-101626469-C-G			Uncertain significance (May 21, 2024)
6-101626504-C-A		Neurodevelopmental disorder with impaired language and ataxia and with or without seizures	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRIK2	protein_coding	protein_coding	ENST00000421544	16	671295

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00159	125734	0	9	125743	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.91	319	502	0.635	0.0000261	5962
Missense in Polyphen		102	232.2	0.43927		2775
Synonymous	-0.497	190	181	1.05	0.00000988	1723
Loss of Function	5.41	6	45.2	0.133	0.00000245	529

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000623	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 (PubMed:28180184). May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity). {ECO:0000250|UniProtKB:P39087, ECO:0000269|PubMed:28180184}.
• Disease: DISEASE: Mental retardation, autosomal recessive 6 (MRT6) [MIM:611092]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. In contrast to syndromic or specific mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic mental retardation. MRT6 patients display mild to severe mental retardation and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal. {ECO:0000269|PubMed:17847003}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Splicing factor NOVA regulated synaptic proteins;Activation of Ca-permeable Kainate Receptor;Ionotropic activity of kainate receptors;Activation of kainate receptors upon glutamate binding;Neuronal System;Activation of Na-permeable kainate receptors;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Intolerance Scores

• loftool: 0.0927
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.48

Haploinsufficiency Scores

• pHI: 0.536
• hipred: Y
• hipred_score: 0.749
• ghis: 0.610

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grik2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: behavioral fear response;cellular calcium ion homeostasis;glutamate receptor signaling pathway;chemical synaptic transmission;neuronal action potential;ion transmembrane transport;ionotropic glutamate receptor signaling pathway;synaptic transmission, glutamatergic;receptor clustering;negative regulation of neuron apoptotic process;positive regulation of neuron apoptotic process;regulation of JNK cascade;regulation of long-term neuronal synaptic plasticity;regulation of short-term neuronal synaptic plasticity;modulation of chemical synaptic transmission;positive regulation of synaptic transmission;neuron apoptotic process;negative regulation of synaptic transmission, glutamatergic;excitatory postsynaptic potential;inhibitory postsynaptic potential;regulation of presynaptic membrane potential
• Cellular component: plasma membrane;integral component of plasma membrane;postsynaptic density;cell junction;dendrite cytoplasm;kainate selective glutamate receptor complex;presynaptic membrane;terminal bouton;perikaryon;postsynaptic membrane;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse
• Molecular function: extracellularly glutamate-gated ion channel activity;glutamate receptor activity;kainate selective glutamate receptor activity;PDZ domain binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase binding;protein homodimerization activity;ligand-gated ion channel activity involved in regulation of presynaptic membrane potential;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential