Evidence map›Paper›PMID 33010019›Full record

ArticleCellular and molecular neurobiology2021

Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.

Marjo Piltonen, Andrey Krokhotin, Marc Parisien, Pierre Bérubé, Haig Djambazian, Rob Sladek, Nikolay V Dokholyan, Svetlana A Shabalina, Luda Diatchenko

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 44% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Morphine-inducedFrontiers in neuroscience · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

Marjo PiltonenSchool of Dentistry, McGill University, Genome Building, Room 2201, 740 Dr. Penfield Avenue, Montreal, Quebec, H3A 0G1, Canada.
Andrey KrokhotinDepartments of Pathology, Genetics and Developmental Biology, Stanford Medical School, Howard Hughes Medical Institute, Palo Alto, CA, 94305, USA.
Marc ParisienSchool of Dentistry, McGill University, Genome Building, Room 2201, 740 Dr. Penfield Avenue, Montreal, Quebec, H3A 0G1, Canada.ORCID http://orcid.org/0000-0003-2924-5960
Pierre BérubéDepartments of Human Genetics and Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 0G1, Canada.
Haig DjambazianDepartments of Human Genetics and Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 0G1, Canada.
Rob SladekDepartments of Human Genetics and Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 0G1, Canada.
Nikolay V DokholyanDepartments of Pharmacology, and Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.
Svetlana A ShabalinaNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, Room S604, 8600 Rockville Pike MSC 3830, Bethesda, MD, 20894-6075, USA. shabalin@ncbi.nlm.nih.gov.
Luda DiatchenkoSchool of Dentistry, McGill University, Genome Building, Room 2201, 740 Dr. Penfield Avenue, Montreal, Quebec, H3A 0G1, Canada. luda.diatchenko@mcgill.ca.
McGill Genome Centre · CAMcGill University and Génome Québec Innovation Centre · CAHoward Hughes Medical Institute · USMcGill University · CANational Institutes of Health · USPennsylvania State University · US

Funding

Nanoscale programming of cellular and physiological phenotypes: EquipmentR35GM134864 · NIGMS · UNIVERSITY OF VIRGINIA · PI Nikolay Dokholyan · 2020 to 2026
$5.2M
NIGMS NIH HHS R35 GM134864
6 · The paper itself

Abstract

The opioid receptor (OPR) family comprises the mu-, delta-, and kappa-opioid, and nociceptin receptors that belong to the superfamily of 7-transmembrane spanning G protein-coupled receptors (GPCRs). The mu-opioid receptor is the main target for clinically used opioid analgesics, and its biology has been extensively studied. The N-terminally truncated 6TM receptors isoform produced through alternative splicing of the OPRM1 gene displays unique signaling and analgesic properties, but it is unclear if other OPRs have the same ability. In this study, we have built a comprehensive map of alternative splicing events that produce 6TM receptor variants in all the OPRs and demonstrated their evolutionary conservation. We then obtained evidence for their translation through ribosomal footprint analysis. We discovered that N-terminally truncated 6TM GPCRs are rare in the human genome and OPRs are overrepresented in this group. Finally, we also observed a significant enrichment of 6TM GPCR genes among genes associated with pain, psychiatric disorders, and addiction. Understanding the biology of 6TM receptors and leveraging this knowledge for drug development should pave the way for novel therapies.

Indexed as

Alternative SplicingAnimalsCell Line, TumorConserved SequenceDatabases, GeneticGenetic VariationHumansMacacaMiceNociceptin ReceptorReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, muSpecies SpecificityNociceptin ReceptorOPRD1 protein, humanOPRK1 protein, humanOPRM1 protein, humanReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, muAlternative splicingEvolutionary conservationGene enrichmentOpioid receptor

Identifiers

PMID33010019
PMCPMC8159799
OpenAlexW3090039959

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.