GRIK3

protein-coding

glutamate ionotropic receptor kainate type subunit 3, 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. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000831.4

Inheritance

—

ClinVar variants

U:110B:13

Top phenotype

GRIK3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr1:36,795,527-37,034,515

External References & Databases

Ensembl (ENSG00000163873)

Transcript & Mutation Effects

hg38 • Region Span ~239.0 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 GRIK3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 17

GRIK3-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000831.4. 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	4 clinvar	7 clinvar	12
missense			104 clinvar	2 clinvar		106
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	110	6	7	123

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000831.4	RefSeq	NP_000822.2	16	MANE Select
ENST00000373091.8	Ensembl	ENSP00000362183.3	16	MANE Select
ENST00000373093.4	Ensembl	ENSP00000362185.4	15	Standard
ENST00000373093.5	Ensembl	ENSP00000362185.4	15	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
Presynaptic function of Kainate receptors

Biological Process

adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
glutamate receptor signaling pathway
G protein-coupled glutamate receptor signaling pathway
ion transmembrane transport
ionotropic glutamate receptor signaling pathway

Molecular Function

adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
G protein-coupled receptor binding
ionotropic glutamate receptor activity
glutamate receptor activity
kainate selective glutamate receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
cell junction
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373091
Coding exons: 16
Length: 238603
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125745
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.01	386	592	0.652	0.0000380	6031
Missense (PolyPhen)		105	231.2	0.45415		2430
Synonymous	-0.400	264	256	1.03	0.0000185	1821
Loss of Function	5.86	4	47.6	0.0840	0.00000275	467

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.00441
RVIS EVS: -1.68
RVIS percentile EVS: 2.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.935

Gene Damage Prediction

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