GRM5
protein-codingglutamate metabotropic receptor 5, the group of Glutamate metabotropic receptors|Protein phosphatase 1 regulatory subunits
Gene summary
This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~561.4 kbGenCC 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 GRM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001143831.3. 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 | 24 | 12 | 37 | ||
| missense | 128 | 3 | 2 | 133 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 130 | 27 | 14 | 171 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001137303.1 | 9 | MANE Select | |
| Ensembl | ENSP00000306138.4 | 9 | MANE Select | |
| RefSeq | NP_000833.1 | 8 | Standard | |
| RefSeq | NP_001371197.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Long-term potentiation - Homo sapiens (human)
- Retrograde endocannabinoid signaling - Homo sapiens (human)
- Glutamatergic synapse - Homo sapiens (human)
- Huntington,s disease - Homo sapiens (human)
- Gap junction - Homo sapiens (human)
Biological Process
- regulation of protein phosphorylation
- regulation of translation
- regulation of translational elongation
- G protein-coupled receptor signaling pathway
- phospholipase C-activating G protein-coupled glutamate receptor signaling pathway
Molecular Function
- G protein-coupled receptor activity
- protein binding
- glutamate receptor activity
- protein tyrosine kinase activator activity
- G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- neuron projection
- Schaffer collateral - CA1 synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000418177
- Coding exons
- 9
- Length
- 561370
- 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 | 3.21 | 425 | 656 | 0.648 | 0.0000341 | 7885 |
| Missense (PolyPhen) | 150 | 356.73 | 0.42049 | 4316 | ||
| Synonymous | -2.25 | 308 | 262 | 1.18 | 0.0000140 | 2432 |
| Loss of Function | 5.24 | 5 | 41.4 | 0.121 | 0.00000223 | 504 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000046 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity. {ECO:0000269|PubMed:25042998, ECO:0000269|PubMed:7908515}.;
Recessive Scores
- pRec
- 0.187
Intolerance Scores
- LoFtool
- 0.00978
- RVIS EVS
- -1.26
- RVIS percentile EVS
- 5.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.327
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |