GRM3
protein-codingglutamate metabotropic receptor 3, the group of Glutamate metabotropic receptors
Gene summary
L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~221.0 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 GRM3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000840.3. 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 | 3 | 6 | 3 | 12 | ||
| missense | 48 | 1 | 1 | 50 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 52 | 7 | 4 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000831.2 | 5 | MANE Select | |
| Ensembl | ENSP00000355316.2 | 5 | MANE Select | |
| RefSeq | NP_001350451.1 | 4 | Standard | |
| Ensembl | ENSP00000390037.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutamatergic synapse - Homo sapiens (human)
- Phospholipase D signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Cocaine addiction - Homo sapiens (human)
- GPCRs, Class C Metabotropic glutamate, pheromone
Biological Process
- G protein-coupled receptor signaling pathway
- negative regulation of adenylate cyclase activity
- adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
- G protein-coupled glutamate receptor signaling pathway
- chemical synaptic transmission
Molecular Function
- group II metabotropic glutamate receptor activity
- G protein-coupled receptor activity
- calcium channel regulator activity
- glutamate receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- postsynaptic density
- axon
- dendritic spine
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361669
- Coding exons
- 5
- Length
- 220971
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.20 | 323 | 530 | 0.609 | 0.0000323 | 5782 |
| Missense (PolyPhen) | 109 | 244.47 | 0.44586 | 2681 | ||
| Synonymous | 0.784 | 205 | 220 | 0.933 | 0.0000147 | 1738 |
| Loss of Function | 4.21 | 6 | 31.5 | 0.191 | 0.00000169 | 366 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 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 inhibits adenylate cyclase activity. {ECO:0000269|PubMed:8840013}.;
Recessive Scores
- pRec
- 0.255
Intolerance Scores
- LoFtool
- 0.0728
- RVIS EVS
- -1.29
- RVIS percentile EVS
- 5.08
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.674
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |