OPRL1
Chr 20opioid related nociceptin receptor 1
Also known as: KOR-3, KOR3, NOCIR, NOP, NOPr, OOR, OPRL, ORL1
The protein is a G-protein coupled receptor that binds the neuropeptide nociceptin and modulates pain perception, locomotor activity, stress responses, and learning and memory through inhibition of adenylate cyclase and calcium channel activity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.617), but no established human disease associations with OPRL1 mutations are currently documented in the provided data. This receptor system represents a potential therapeutic target for pain and neuropsychiatric conditions, though its role in pediatric neurogenetic disorders remains to be established.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
153 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 | 30 | 0 | 30 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 96 | 9 | 0 | 105 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 1 | 3 | 4 |
| Total | 0 | 99 | 47 | 3 | 149 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
OPRL1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools