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 p... See more...

Aliases for CNR2 Gene

Aliases for CNR2 Gene

  • Cannabinoid Receptor 2 2 3 4 5
  • CB2 2 3 4
  • Cannabinoid Receptor 2 (Macrophage) 2 3
  • CB-2 3 4
  • CX5 3 4
  • CNR2 5
  • CB2A 4
  • CB2B 4
  • HCB2 4

External Ids for CNR2 Gene

Previous GeneCards Identifiers for CNR2 Gene

  • GC01M023725
  • GC01M023271
  • GC01M9A0006
  • GC01M9A3945
  • GC01M023945
  • GC01M024069
  • GC01M024197
  • GC01M022452

Summaries for CNR2 Gene

Entrez Gene Summary for CNR2 Gene

  • 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]

GeneCards Summary for CNR2 Gene

CNR2 (Cannabinoid Receptor 2) is a Protein Coding gene. Diseases associated with CNR2 include Cannabis Abuse and Polyarticular Juvenile Idiopathic Arthritis. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and cannabinoid receptor activity. An important paralog of this gene is CNR1.

UniProtKB/Swiss-Prot Summary for CNR2 Gene

  • Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.

Tocris Summary for CNR2 Gene

  • The CB2 receptor, also known as the peripheral cannabinoid receptor, is a member of the cannabinoid receptor group of G-protein-coupled receptors that also includes CB1 and GPR55. CB2 receptors are located primarily in immune cells both within and outside the CNS.

Gene Wiki entry for CNR2 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CNR2 Gene

Genomics for CNR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CNR2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CNR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CNR2

Top Transcription factor binding sites by QIAGEN in the CNR2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • CREB
  • deltaCREB
  • GR
  • GR-alpha
  • STAT1
  • STAT5A

Genomic Locations for CNR2 Gene

Latest Assembly
chr1:23,870,515-23,913,362
(GRCh38/hg38)
Size:
42,848 bases
Orientation:
Minus strand

Previous Assembly
chr1:24,197,005-24,239,852
(GRCh37/hg19 by Entrez Gene)
Size:
42,848 bases
Orientation:
Minus strand

chr1:24,197,016-24,285,549
(GRCh37/hg19 by Ensembl)
Size:
88,534 bases
Orientation:
Minus strand

Genomic View for CNR2 Gene

Genes around CNR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CNR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CNR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CNR2 Gene

Proteins for CNR2 Gene

  • Protein details for CNR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P34972-CNR2_HUMAN
    Recommended name:
    Cannabinoid receptor 2
    Protein Accession:
    P34972
    Secondary Accessions:
    • C6ES44
    • Q4VBK8
    • Q5JRH7
    • Q6B0G7
    • Q6NSY0

    Protein attributes for CNR2 Gene

    Size:
    360 amino acids
    Molecular mass:
    39681 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for CNR2 Gene

neXtProt entry for CNR2 Gene

Post-translational modifications for CNR2 Gene

  • Constitutively phosphorylated on Ser-352; phosphorylation increases cell internalization and desensitizes the receptor.
  • Glycosylation at Asn11
  • Modification sites at PhosphoSitePlus

Other Protein References for CNR2 Gene

No data available for DME Specific Peptides for CNR2 Gene

Domains & Families for CNR2 Gene

Gene Families for CNR2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • G-protein coupled receptors
  • Predicted membrane proteins
  • Transporters

Protein Domains for CNR2 Gene

InterPro:
Blocks:
  • Cannabinoid receptor signature
  • Cannabinoid receptor type 2 signature

Suggested Antigen Peptide Sequences for CNR2 Gene

GenScript: Design optimal peptide antigens:
  • Testis-dominant CNR2 isoform CB2 (C6ES44_HUMAN)
  • CX5 (CNR2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P34972

UniProtKB/Swiss-Prot:

CNR2_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with CNR2: view

Function for CNR2 Gene

Molecular function for CNR2 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
In macrophages, down-regulated by endocannabinoid anandamide/AEA.
GENATLAS Biochemistry:
cannabinoid receptor 2,peripheral,expressed in spleen,inhibiting adenylate cyclase

Phenotypes From GWAS Catalog for CNR2 Gene

Gene Ontology (GO) - Molecular Function for CNR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IBA 21873635
GO:0004949 cannabinoid receptor activity IBA 21873635
GO:0005515 protein binding IPI 28843453
genes like me logo Genes that share ontologies with CNR2: view
genes like me logo Genes that share phenotypes with CNR2: view

Animal Models for CNR2 Gene

MGI Knock Outs for CNR2:

miRNA for CNR2 Gene

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CNR2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CNR2 Gene

Localization for CNR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CNR2 Gene

Cell membrane. Multi-pass membrane protein. Cell projection, dendrite. Perikaryon. Note=Localizes to apical dendrite of pyramidal neurons. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CNR2 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 4
extracellular 2
cytoskeleton 2
mitochondrion 2
nucleus 2
peroxisome 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for CNR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005783 endoplasmic reticulum IDA 28364261
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 8679694
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with CNR2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CNR2 Gene

Pathways & Interactions for CNR2 Gene

genes like me logo Genes that share pathways with CNR2: view

Pathways by source for CNR2 Gene

1 KEGG pathway for CNR2 Gene
1 Qiagen pathway for CNR2 Gene
  • Reelin Pathway (Cajal-Retzius cells)

SIGNOR curated interactions for CNR2 Gene

Activates:

Gene Ontology (GO) - Biological Process for CNR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001975 response to amphetamine IEA --
GO:0006954 inflammatory response IEA --
GO:0006955 immune response TAS 7556170
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with CNR2: view

Drugs & Compounds for CNR2 Gene

(76) Drugs for CNR2 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dronabinol Approved, Illicit Pharma Target, agonist 216
Nabilone Approved, Investigational Pharma Target, partial agonist 26
cannabidiol Approved, Investigational Pharma Target, antagonist 0
Rimonabant Approved, Investigational Pharma CB1 receptor antagonist 46
Lasofoxifene Approved, Investigational Pharma Target, inverse agonist 0

(15) Additional Compounds for CNR2 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
GW 405833
180002-83-9
JWH 015
155471-08-2
JWH 133
259869-55-1
JWH 133 (in Tocrisolve 100)
259869-55-1

(5) Tocris Compounds for CNR2 Gene

Compound Action Cas Number
GW 405833 Selective, high affinity CB2 receptor partial agonist 180002-83-9
JWH 015 Selective CB2 agonist 155471-08-2
JWH 133 Potent, selective CB2 agonist 259869-55-1
JWH 133 (in Tocrisolve 100) Potent, selective CB2 agonist (in water-soluble emulsion) 259869-55-1
L-759,633 High affinity, selective CB2 agonist 174627-50-0

(35) ApexBio Compounds for CNR2 Gene

Compound Action Cas Number
2-Palmitoylglycerol 23470-00-0
AM 1172 Inhibitor of anandamide uptake and FAAH,potent and selective 251908-92-6
AM1241 Cannabinoid CB2 receptor agonist,potent and selective 444912-48-5
AM251 Potent CB1 antagonist 183232-66-8
AM630 CB2 receptor antagonist,selective and competitive 164178-33-0
Arachidonyl serotonin 187947-37-1
Arvanil 128007-31-8
BML-190 CB2 receptor ligand 2854-32-2
COR 170 1048039-15-1
CP-945598 HCl CB1 antagonist,selective and high affinity 686347-12-6
GW842166X 666260-75-9
Hemopressin (human, mouse) 1314035-51-2
Hemopressin (rat) 568588-77-2
HU 308 CB2-receptor agonist 256934-39-1
JTE 907 282089-49-0
LY 320135 176977-56-3
MAFP 188404-10-6
MJ 15 944154-76-1
MM-22 956605-71-3
N-Arachidonylglycine 179113-91-8
NIDA 41020 502486-89-7
O-1918 536697-79-7
O-2050
O-2093 439080-01-0
Oleamide 301-02-0
OMDM-2 616884-63-0
Org 27569 Cannabinoid CB1 receptor allosteric modulator 868273-06-7
Palmitoylisopropylamide 189939-61-5
PF 514273 851728-60-4
Rimonabant CB1 receptor antagonist 168273-06-1
Taranabant 701977-09-5
TC-C 14G 656804-72-7
Tocrifluor T1117 1186195-59-4
UCM 707 390824-20-1
VDM 11 313998-81-1
genes like me logo Genes that share compounds with CNR2: view

Drug products for research

Transcripts for CNR2 Gene

mRNA/cDNA for CNR2 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CNR2

Alternative Splicing Database (ASD) splice patterns (SP) for CNR2 Gene

No ASD Table

Relevant External Links for CNR2 Gene

GeneLoc Exon Structure for
CNR2

Expression for CNR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CNR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CNR2 Gene

This gene is overexpressed in Spleen (x19.6), Small Intestine - Terminal Ileum (x7.1), and Whole Blood (x7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CNR2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CNR2

SOURCE GeneReport for Unigene cluster for CNR2 Gene:

Hs.73037

mRNA Expression by UniProt/SwissProt for CNR2 Gene:

P34972-CNR2_HUMAN
Tissue specificity: Preferentially expressed in cells of the immune system with higher expression in B-cells and NK cells (at protein level). Expressed in skin in suprabasal layers and hair follicles (at protein level). Highly expressed in tonsil and to a lower extent in spleen, peripheral blood mononuclear cells, and thymus. PubMed:14657172 could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root ganglion sensory neurons (at protein level). Two isoforms are produced by alternative promoter usage and differ only in the 5' UTR: isoform CB2A is observed predominantly in testis with some expression in brain, while isoform CB2B is predominant in spleen and leukocytes.

Evidence on tissue expression from TISSUES for CNR2 Gene

  • Nervous system(4.5)
  • Blood(4.5)
  • Spleen(4.4)
  • Skin(2.3)
  • Intestine(2.3)
genes like me logo Genes that share expression patterns with CNR2: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CNR2 Gene

Orthologs for CNR2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CNR2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CNR2 29 30
  • 99.26 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CNR2 29 30
  • 85 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CNR2 29 30
  • 84.22 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Cnr2 29 16 30
  • 82.32 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cnr2 29
  • 81.85 (n)
Oppossum
(Monodelphis domestica)
Mammalia CNR2 30
  • 68 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CNR2 30
  • 57 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CNR2 29 30
  • 56.11 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CNR2 30
  • 54 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cnr2 29
  • 54.98 (n)
Zebrafish
(Danio rerio)
Actinopterygii cnr2 29 30
  • 51.04 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 23 (a)
ManyToMany
-- 30
  • 21 (a)
ManyToMany
Species where no ortholog for CNR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CNR2 Gene

ENSEMBL:
Gene Tree for CNR2 (if available)
TreeFam:
Gene Tree for CNR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CNR2: view image
Alliance of Genome Resources:
Additional Orthologs for CNR2

Paralogs for CNR2 Gene

(1) SIMAP similar genes for CNR2 Gene using alignment to 1 proteins:

  • CNR2_HUMAN
genes like me logo Genes that share paralogs with CNR2: view

Variants for CNR2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CNR2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs144279977 Likely Benign: not provided 23,875,327(-) G/A
NM_001841.3(CNR2):c.291C>T (p.Phe97=)
SYNONYMOUS
rs201210941 Benign: not provided 23,874,679(-) G/A
NM_001841.3(CNR2):c.939C>T (p.Cys313=)
SYNONYMOUS
rs61996280 Benign: not provided 23,875,421(-) C/T
NM_001841.3(CNR2):c.197G>A (p.Arg66Gln)
MISSENSE
rs2229579 -- p.His316Tyr
rs2501432 -- p.Gln63Arg

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CNR2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CNR2 Gene

Variant ID Type Subtype PubMed ID
dgv190n54 CNV loss 21841781
dgv191n54 CNV loss 21841781
dgv29n67 CNV loss 20364138
esv1663042 CNV insertion 17803354
esv2672735 CNV deletion 23128226
esv2745386 CNV deletion 23290073
esv29329 CNV loss 19812545
esv3585494 CNV loss 21293372
esv3585495 CNV loss 21293372
esv3893081 CNV gain 25118596
esv991485 CNV insertion 20482838
nsv1122310 CNV deletion 24896259
nsv1133021 OTHER inversion 24896259
nsv1145326 CNV deletion 24896259
nsv512727 CNV insertion 21212237
nsv545778 CNV loss 21841781

Variation tolerance for CNR2 Gene

Residual Variation Intolerance Score: 39.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.18; 39.42% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CNR2 Gene

Human Gene Mutation Database (HGMD)
CNR2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CNR2
Leiden Open Variation Database (LOVD)
CNR2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CNR2 Gene

Disorders for CNR2 Gene

MalaCards: The human disease database

(9) MalaCards diseases for CNR2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
cannabis abuse
  • marijuana abuse
polyarticular juvenile idiopathic arthritis
  • juvenile polyarthritis
chlorhexidine allergy
advanced sleep phase syndrome, familial, 3
  • fasps3
multiple sclerosis
  • multiple sclerosis, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search CNR2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CNR2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CNR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CNR2 Gene

Publications for CNR2 Gene

  1. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. (PMID: 18286196) Onaivi ES … Uhl GR (PloS one 2008) 3 4 22 40
  2. Hepatic expression of endocannabinoid receptors and their novel polymorphisms in primary biliary cirrhosis. (PMID: 19730968) Floreani A … Bergasa NV (Journal of gastroenterology 2010) 3 22 40
  3. Brain cannabinoid CB2 receptor in schizophrenia. (PMID: 19931854) Ishiguro H … Arinami T (Biological psychiatry 2010) 3 22 40
  4. Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. (PMID: 19496827) Liu QR … Uhl GR (Genes, brain, and behavior 2009) 3 4 22
  5. The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample. (PMID: 19565271) Karsak M … Livshits G (Human genetics 2009) 3 22 40

Products for CNR2 Gene

Sources for CNR2 Gene