GRIK4
protein-codingglutamate ionotropic receptor kainate type subunit 4, 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
- GRIK
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~477.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: The choice of medications may be affected by the presence of variants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GRIK4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014619.5. 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 | 2 | 21 | 5 | 28 | ||
| missense | 130 | 1 | 5 | 136 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 134 | 22 | 10 | 166 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055434.2 | 19 | MANE Select | |
| Ensembl | ENSP00000435648.2 | 19 | MANE Select | |
| RefSeq | NP_001269399.1 | 19 | Standard | |
| RefSeq | NP_001269402.1 | 16 | 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
- ion transmembrane transport
- ionotropic glutamate receptor signaling pathway
- synaptic transmission, glutamatergic
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:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000527524
- Coding exons
- 19
- Length
- 477146
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.04 | 436 | 574 | 0.760 | 0.0000347 | 6211 |
| Missense (PolyPhen) | 154 | 241.31 | 0.63818 | 2606 | ||
| Synonymous | -0.191 | 242 | 238 | 1.02 | 0.0000157 | 1884 |
| Loss of Function | 4.65 | 11 | 44.5 | 0.247 | 0.00000208 | 510 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.208
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 20
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.103
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |