ArticleCell2019
Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.
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In one paragraph
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed, 4 pooled it
15.3field-weighted citation impact, top 1% of its field
What it found
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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
157 citing papers in PubMed, 4 syntheses or guidelines pooled it, 278 citations in OpenAlex.
- Pooled it
- The Genetic Basis of Childhood Obesity: A Systematic Review.Nutrients · 2023Pooled it
- The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes.EBioMedicine · 2020Pooled it
- Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.Nature medicine · 2025Trial
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Attractin-like protein 1 is an essential partner of MC4R to regulate body weight.Nature communications · 2026Article
- Genetic research on childhood obesity and asthma: exploring genetic risk factors and biological mechanisms.Pediatric research · 2026Review
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Primary cilia dysfunction: A critical driver of metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Primary Cilia as Integrative Hubs of Metabolic Signaling in Type 2 Diabetes: Inter-Organ Evidence From Central, Peripheral, and Pancreatic Islet Tissues.Journal of cellular physiology · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- The anti-inflammatory efficacy of melanocortin drugs is influenced by genetic variation at MC1R.Scientific reports · 2026Article
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Mice lacking β-arrestin-2 in melanocortin 4 receptor-expressing neurons show marked metabolic deficits.JCI insight · 2026Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations.Molecular metabolism · 2026Article
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 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
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Luca A LottaUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: luca.lotta@mrc-epid.cam.ac.uk.
Jacek MokrosińskiUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Edson Mendes de OliveiraUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Chen LiUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Stephen J SharpUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Jian'an LuanUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Bas BrouwersUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Vikram AyinampudiUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Nicholas BowkerUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Nicola KerrisonUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Vasileios KaimakisUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Diana HoultUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Isobel D StewartUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Eleanor WheelerUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Felix R DayUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
John R B PerryUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Claudia LangenbergUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Nicholas J WarehamUniversity of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
I Sadaf FarooqiUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: isf20@cam.ac.uk.
Wellcome Trust · GBAddenbrooke's Hospital · GBMRC Epidemiology Unit · GBUniversity of Cambridge · GB
Funding
Department of HealthMedical Research Council MC_PC_13046Medical Research Council MC_PC_13048Medical Research Council MC_UU_00014/1Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/2Medical Research Council MR/L00002/1Wellcome Trust 098497/Z/12/ZWellcome Trust 208363/Z/17/Z
Abstract
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor whose disruption causes obesity. We functionally characterized 61 MC4R variants identified in 0.5 million people from UK Biobank and examined their associations with body mass index (BMI) and obesity-related cardiometabolic diseases. We found that the maximal efficacy of β-arrestin recruitment to MC4R, rather than canonical Gα
Indexed as
Signal TransductionAdultAgedbeta-ArrestinsBody Mass IndexCoronary Artery DiseaseCyclic AMPDatabases, FactualDiabetes Mellitus, Type 2FemaleGain of Function MutationGenetic Predisposition to DiseaseGenotypeGTP-Binding Protein alpha Subunits, GsHumansMalebeta-ArrestinsCyclic AMPGTP-Binding Protein alpha Subunits, GsMC4R protein, humanReceptor, Melanocortin, Type 4biased signalinggeneticsGPCRsMC4RmelanocortinobesityUK Biobankβ-arrestin
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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.