ArticleCell2013
KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 4 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 4 syntheses or guidelines pooled it, 197 citations in OpenAlex.
- Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis.Biology of sex differences · 2024Pooled it
- Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes.Nature communications · 2019Pooled it
- Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nature genetics · 2019Pooled it
- A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.Nature genetics · 2015Pooled it
- Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study.Frontiers in endocrinology · 2023Trial
- Leptin-Mediated Changes in the Human Metabolome.The Journal of clinical endocrinology and metabolism · 2020Trial
- A single mechanism can explain network-wide insulin resistance in adipocytes from obese patients with type 2 diabetes.The Journal of biological chemistry · 2014Trial
- Genetic variants of the leptin-melanocortin pathway in a clinically selected Greek cohort with severe early-onset obesity and hyperphagia: implications for precision obesity medicine.Obesity pillars · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- KSR2 functions as a metabolic checkpoint for anti-PD-1 resistance by reprogramming glucose metabolism.Cancer immunology, immunotherapy : CII · 2026Article
- The genetics of obesity: aetiology, prevention and therapy.Nature metabolism · 2026Review
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Targeted Next-Generation Sequencing of the Leptin-Melanocortin Pathway in Severe Obesity.Obesity (Silver Spring, Md.) · 2026Article
- Endothelial KSR2 regulated by genetic variation protects against atherosclerosis through AMPKα1 stabilization.Theranostics · 2026Article
- Effects of Rare Coding Variants in Severe Early-Onset Obesity Genes in the Population-Based UK Biobank Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Differential Genetic Architecture of Insulin Resistance (HOMA-IR) Based on Obesity Status: Evidence from a Large-Scale GWAS of Koreans.Current issues in molecular biology · 2025Article
- Obese-diabetic femaleJBMR plus · 2025Article
- The Interplay of UCP3 and PCSK1 Variants in Severe Obesity.Current obesity reports · 2025Review
- Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.Archives of endocrinology and metabolism · 2025Article
- Obesity: exploring its connection to brain function through genetic and genomic perspectives.Molecular psychiatry · 2025Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 9 institutions in 2 countries.
Funding
Abstract
Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.
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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.