GRIK1

protein-coding

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

Gene summary

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to alter the properties of ion flow. Alternative splicing, resulting in transcript variants encoding different isoforms, has been noted for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

GLUR5

MANE transcript

NM_001330994.2

Inheritance

—

ClinVar variants

U:132B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr21:29,536,933-29,940,033

External References & Databases

Ensembl (ENSG00000171189)

Transcript & Mutation Effects

hg38 • Region Span ~403.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRIK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 15

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330994.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	10 clinvar	3 clinvar	14
missense			131 clinvar	1 clinvar		132
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	132	11	3	146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330994.2	RefSeq	NP_001317923.1	18	MANE Select
ENST00000327783.9	Ensembl	ENSP00000327687.4	18	MANE Select
NM_000830.6	RefSeq	NP_000821.1	17	Standard
NM_001320616.2	RefSeq	NP_001307545.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glutamatergic synapse - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Activation of Ca-permeable Kainate Receptor
Ionotropic activity of kainate receptors
Activation of kainate receptors upon glutamate binding

Biological Process

glutamate receptor signaling pathway
chemical synaptic transmission
nervous system development
central nervous system development
ion transmembrane transport

Molecular Function

glutamate receptor activity
kainate selective glutamate receptor activity
transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential

Cellular Component

plasma membrane
integral component of plasma membrane
cell junction
kainate selective glutamate receptor complex
presynaptic membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399907
Coding exons: 17
Length: 403098
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	440	510	0.862	0.0000274	6019
Missense (PolyPhen)		139	203.49	0.68308		2395
Synonymous	-0.497	210	201	1.04	0.0000119	1755
Loss of Function	3.03	22	43.6	0.504	0.00000204	536

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00043	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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. May be involved in the transmission of light information from the retina to the hypothalamus.;

Recessive Scores

pRec: 0.550

Intolerance Scores

LoFtool: 0.227
RVIS EVS: -1.64
RVIS percentile EVS: 2.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.810

Gene Damage Prediction

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