ArticleeLife2025
High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed.
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- The GPCRDiabetologia · 2026Article
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- A cost-effective and scalable barcoded library construction method for deep mutational scanning studies.PLoS biology · 2026Article
- A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.Cell genomics · 2025Article
- Decoding missense variants pleiotropy in the immune GPCR P2RY8.Cell genomics · 2025Article
- Characterizing Variants of Uncertain Drug Resistance (VUDRs) Using Quantitative Measurements at Clinical Exposures.bioRxiv : the preprint server for biology · 2025Article
- Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes.Nature communications · 2025Article
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Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Deep Mutational Scanning (DMS) is an emerging method to systematically test the functional consequences of thousands of sequence changes to a protein target in a single experiment. Because of its utility in interpreting both human variant effects and protein structure-function relationships, it holds substantial promise to improve drug discovery and clinical development. However, applications in this domain require improved experimental and analytical methods. To address this need, we report novel DMS methods to precisely and quantitatively interrogate disease-relevant mechanisms, protein-ligand interactions, and assess predicted response to drug treatment. Using these methods, we performed a DMS of the melanocortin-4 receptor (MC4R), a G-protein-coupled receptor (GPCR) implicated in obesity and an active target of drug development efforts. We assessed the effects of >6600 single amino acid substitutions on MC4R's function across 18 distinct experimental conditions, resulting in >20 million unique measurements. From this, we identified variants that have unique effects on MC4R-mediated Gα
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Registered trials
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.