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FLASH GENE

Symbol

CNR1

contributors: mct/npt - updated : 09-07-2017

HGNC name	cannabinoid receptor 1 (brain)
HGNC id	2159

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	26.18 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016083 2 - 5732 NP_057167 52.8 472 - 2008 18285348 CNR1 Ia NM_033181 2 - 5387 NP_149421 - 439 - 2008 18285348 CNR1 Ib NM_001160226 3 - 5863 NP_001153698 52.8 472 - 2008 18285348 NM_001160258 4 - 5901 NP_001153730 52.8 472 - 2008 18285348 NM_001160259 2 - 5776 NP_001153731 52.8 472 - 2008 18285348

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Homo sapiens Lymphoid/Immune lymph node       highly Nervous brain       predominantly Homo sapiens Urinary kidney tubule collecting duct     Homo sapiens   kidney tubule convoluted tubule     Homo sapiens Visual eye anterior segment cornea       eye uvea ciliary body

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective         Muscular striatum     highly Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	expressed in the subventricular zone and in Cajal-Retzius cells in the molecular zone of the developing neocortex
	expression in fetal and adult kidneys

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor
	C-terminus, having critical structures that are important for CB(1) activity and regulation

HOMOLOGY

Homologene

FAMILY

G protein coupled receptor superfamily

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,microsome

basic FUNCTION	inhibiting adenylate cyclase located in and/or one cone pedicles and rod spherules
	also inhibiting voltage-gated L-type calcium channel current in retinal bipolar cells
	putatively involved for endogenous cannabinoid system in retinal physiology
	play an unexpected role in dorsal horn pain-controlling circuits
	participated in the regulation of lipid metabolism in human-derived immortalized hepatocytes by regulating the expression of key enzymes of lipid synthesis and transport
	potential function in the early stages of corticogenesis
	having a role in the regulation of bone mass
	responsible for the psychotropic action of cannabinoids
	could play an instrumental role in the development and function of the retina (
	seems to be involved in the regulation of the EP300 wave as a marker of selective attention and working memory
	its activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation
	role of CNR1 in the regulation of Neural stem cells (NSCs) fate, suggesting that its activation may represent a pro-neuronal differentiation signal
	endogenous CNR1 activation contributes to vascular SMC proliferation and neointima formation in response to arterial injury
	play a critical role in LPS-induced febrile responses through inhibiting TLR4-mediated cytokine production
	dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior
	is not only associated with phenotypes such as cognitive performance, addiction and anxiety, but is also known to be crucially involved in responses to acute and chronic psychological and cellular stress conditions
	has a major role in the activation of myofibroblasts
	possibility of crosstalk between SST subtypes and CNR1 in regulation of physiological activities in the hippocampus
	participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	CNR1 signaling may thus play a role in physiological cardiorespiratory regulation and protect from some adverse cardiovascular consequences of a high-fat diet (HFD)
	CNR1 signaling contributes to the hyperglycemia disturbance of PPARG2 signaling and increases inflammatory cytokine secretion and fibrotic matrix deposition in renal glomeruli

a component

INTERACTION

DNA

RNA

small molecule

protein	tight control of CNR1 function by ADORA2A in glutamatergic terminals of the striatum
	receptor binding &
	916;(9)-tetrahydrocannabinol, and implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain
	binding between a distal C-terminus fragment of cannabinoid receptor 1 CNR1) and arrestin-2 (ARRB2) (
	ADORA2A and CNR1 may physically and functionally interact
	CNR1 activation did not engage the key regulator of skin pigmentation, cyclic AMP, showing a major difference compared with the regulation of melanogenesis by alpha-melanocyte-stimulating hormone through MC1R
	HINT1 protein cooperates with CNR1 to negatively regulate glutamate NMDA receptor activity
	assembles with multiple members of the WASL complex and the RhoGTPase RAC1 and modulates their activity

cell & other

REGULATION

Other

RARgamma regulates CNR1 expression and is thus involved in the control of hepatic fat metabolism by endocannabinoids

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in clear cell renal cell carcinoma constitutional     --over   might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia constitutional       loss of function alleviates diabetes-mediated renal deterioration constitutional       loss of function combined deficiency of the CNR1 and CNR2 receptors protects against age-related bone loss by osteoclast inhibition

Susceptibility

to anorexia nervosa to obesity related phenotypes to hebephrenic schizophrenia to sensitivity to the acute effects of cannabinoids on EP300 generation in healthy subjects to diabetic nephropathy and diabetic retinopathy in patients with T2DM

Variant & Polymorphism other	variant increasing the risk of obesity related phenotypes
	variant increasing the risk of hebephrenic schizophrenia
	variations within CNR1 may differentially alter the sensitivity to the acute effects of cannabinoids on EP300 generation in healthy subjects
	association of the G1359A polymorphism with diabetic nephropathy and diabetic retinopathy in patients with T2DM

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed osteoarticular bone   treatment of osteoporosis and other bone diseases (antagonists of CNR1) digestive     use of cannabinoid CB(1) receptors in parietal cells as new therapeutic targets for the regulation of gastric acid production diabete type 1   CNR1 inhibition may be beneficial in the treatment of diabetic retinopathy, a devastating complication of diabetes miscelleaneous urinary chronic kidney disease may be a new target for treating chronic kidney disease

ANIMAL & CELL MODELS

	mice lacking the Cnr1 gene, showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus (