GRIK5

protein-coding

glutamate ionotropic receptor kainate type subunit 5, the group of Glutamate ionotropic receptor kainate type subunits

Gene summary

This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Previous symbols:

GRIK2

MANE transcript

NM_002088.5

Inheritance

—

ClinVar variants

U:123B:13

Top phenotype

GRIK5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr19:41,998,321-42,070,206

External References & Databases

Ensembl (ENSG00000105737)

Transcript & Mutation Effects

hg38 • Region Span ~71.9 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 GRIK5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 106

GRIK5-related disorderTotal: 19

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002088.5. 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			4 clinvar	8 clinvar	1 clinvar	13
missense			115 clinvar	3 clinvar	1 clinvar	119
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	123	11	2	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002088.5	RefSeq	NP_002079.3	19	MANE Select
ENST00000593562.6	Ensembl	ENSP00000470251.1	19	MANE Select
NM_001301030.2	RefSeq	NP_001287959.1	19	Standard
ENST00000262895.7	Ensembl	ENSP00000262895.2	19	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

protein retention in ER lumen
regulation of synaptic vesicle fusion to presynaptic active zone membrane
ion transmembrane transport
ionotropic glutamate receptor signaling pathway
synaptic transmission, glutamatergic

Molecular Function

glutamate receptor activity
kainate selective glutamate receptor activity
SH3 domain binding
PDZ domain binding
identical protein binding

Cellular Component

nucleus
endoplasmic reticulum
plasma membrane
cell junction
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262895
Coding exons: 19
Length: 71178
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.36	358	587	0.609	0.0000395	6255
Missense (PolyPhen)		127	253.68	0.50063		2590
Synonymous	0.0562	252	253	0.996	0.0000181	2081
Loss of Function	5.34	7	46.2	0.152	0.00000247	479

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for glutamate. 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 kainate > quisqualate > domoate > L- glutamate >> AMPA >> NMDA = 1S,3R-ACPD.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.144
RVIS EVS: -1.13
RVIS percentile EVS: 6.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.704

Gene Damage Prediction

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