CNR1
Chr 6cannabinoid receptor 1
Also known as: CANN6, CB-R, CB1, CB1A, CB1K5, CB1R, CNR
The protein is a G-protein coupled receptor for endogenous cannabinoids that regulates neurotransmission, energy metabolism, and inflammatory responses throughout the central nervous system and peripheral tissues. Mutations cause early-onset epileptic encephalopathy and neurodevelopmental disorders with seizures, developmental delay, and movement abnormalities. The gene shows autosomal recessive inheritance and demonstrates significant constraint against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
70 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 36 | 4 | 0 | 40 |
Likely Benign | 0 | 0 | 0 | 9 | 9 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 36 | 18 | 10 | 64 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CNR1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
THC Titration of High-Potency Cannabis Concentrates
NOT YET RECRUITINGPilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users
RECRUITINGThe Effect of Different Diets on Arterial Stiffness in Obese Patients on Semaglutide
RECRUITINGPharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes
RECRUITINGIMarkHD: in Vivo Longitudinal Imaging of HD Pathology
RECRUITINGImaging Cannabinoid Receptors Using Positron Emission Tomography (PET) Scanning
RECRUITINGExternal Resources
Links to major genomics databases and tools