CNR2
protein-codingcannabinoid receptor 2, the group of Cannabinoid receptors
Gene summary
The cannabinoid delta-9-tetrahydrocannabinol is the principal psychoactive ingredient of marijuana. The proteins encoded by this gene and the cannabinoid receptor 1 (brain) (CNR1) gene have the characteristics of a guanine nucleotide-binding protein (G-protein)-coupled receptor for cannabinoids. They inhibit adenylate cyclase activity in a dose-dependent, stereoselective, and pertussis toxin-sensitive manner. These proteins have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. The cannabinoid receptors are members of family 1 of the G-protein-coupled receptors. [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 ~42.8 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 CNR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001841.3. 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 | 1 | 2 | |||
| missense | 50 | 1 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 50 | 1 | 2 | 53 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001832.1 | 1 | MANE Select | |
| Ensembl | ENSP00000363596.4 | 1 | MANE Select | |
| Ensembl | ENSP00000810410.1 | 1 | Standard | |
| RefSeq | XP_011538931.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cnr2 | Danio rerio | Structure: hepatocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Small Ligand GPCRs
- Cannabinoid receptor signaling
- Gastric ulcer formation
- GPCRs, Class A Rhodopsin-like
Biological Process
- response to amphetamine
- inflammatory response
- immune response
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
Molecular Function
- cannabinoid receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- dendrite
- extrinsic component of cytoplasmic side of plasma membrane
- perikaryon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536471
- Coding exons
- 1
- Length
- 88534
- Individuals with no LoFs
- 125628
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 119
- Defined
- 125747
- p
- 0.000473
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.681 | 173 | 200 | 0.864 | 0.0000104 | 2316 |
| Missense (PolyPhen) | 53 | 73.413 | 0.72194 | 906 | ||
| Synonymous | -0.314 | 88 | 84.3 | 1.04 | 0.00000430 | 785 |
| Loss of Function | 0.0786 | 8 | 8.24 | 0.970 | 5.21e-7 | 82 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0027 | 0.0027 | notable |
| Finnish | 0.00088 | 0.00088 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00049 | 0.00039 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis. {ECO:0000269|PubMed:10051546, ECO:0000269|PubMed:12663043, ECO:0000269|PubMed:12711605, ECO:0000269|PubMed:18692962}.;
Recessive Scores
- pRec
- 0.452
Intolerance Scores
- LoFtool
- 0.727
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.150
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |