ArticleCell reports2021
Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Interactions between genes altered during cardiotoxicity and neurotoxicity in zebrafish revealed using induced network modules analysis.Scientific reports · 2023Pooled it
- Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.Nature medicine · 2025Trial
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Functional characterisation of obesity-associated MRAP2 variants on MC4R and GHSR signalling.Human molecular genetics · 2026Article
- The Natural History of Prediabetes and Cardiovascular Disease in the Pediatric Population.Biomedicines · 2026Review
- A conserved functional missense SNP (E100K) in sheep MC4R gene leading to functional loss and impacting the growth traits.Journal of animal science · 2026Article
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.Nature medicine · 2025Article
- IMPROVE 2023: The 2nd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2025Article
- Article
- MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants.bioRxiv : the preprint server for biology · 2025Article
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- GPR45 modulates GαScience (New York, N.Y.) · 2025Article
- Article
- Identification and molecular characterization of missense mutations in orphan G protein-coupled receptor GPR61 occurring in severe obesity.Molecular pharmacology · 2025Article
- Canine genome-wide association study identifiesScience (New York, N.Y.) · 2025Article
- Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.Human molecular genetics · 2025Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
The Melanocortin-4 Receptor (MC4R) plays a pivotal role in energy homeostasis. We used human MC4R mutations associated with an increased or decreased risk of obesity to dissect mechanisms that regulate MC4R function. Most obesity-associated mutations impair trafficking to the plasma membrane (PM), whereas obesity-protecting mutations either accelerate recycling to the PM or decrease internalization, resulting in enhanced signaling. MC4R mutations that do not affect canonical 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 Socratic graph.