ArticleThe Journal of clinical investigation2013
Rare variants in single-minded 1 (SIM1) are associated with severe obesity.
Article in The Journal of clinical investigation, 2013. 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 90 papers, 2 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
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 166 citations in OpenAlex.
- Multi-ancestry investigation of the genomics of erectile dysfunction.Nature communications · 2025Pooled it
- Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2017 · on this mapGuideline
- A Batch-Aware, Subject-Grouped Pipeline to Prioritize HIIT-Associated DNA Methylation Candidates with Cross-Cohort Evaluation in Skeletal Muscle.International journal of molecular sciences · 2026Article
- Genetic determinants of obesity: mechanisms, clinical implications, and targeted therapies.Endocrine · 2026Review
- Aryl hydrocarbon receptor nuclear translocator 2: a forgotten per-ARNT-Sim transcription factor.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Hypothalamic obesity.Reviews in endocrine & metabolic disorders · 2026Review
- 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
- Multimodal bHLH-PAS DNA binding controls specificity and drives obesity.Nucleic acids research · 2026Article
- NovelInternational journal of molecular sciences · 2026Article
- Genetic architecture of obesity and advances in precision pharmacotherapy: a comprehensive review.Acta biochimica Polonica · 2026Review
- 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
- Article
- Towards Precision Medicine in Obesity: Genetic Copy Number Variations Profiling Linked to Specific Metabolic Dysregulation Patterns.International journal of molecular sciences · 2025Article
- Canine genome-wide association study identifiesScience (New York, N.Y.) · 2025Article
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Obesity: exploring its connection to brain function through genetic and genomic perspectives.Molecular psychiatry · 2025Review
- Identification and functional validation of rare coding variants in genes linked to monogenic obesity.Obesity (Silver Spring, Md.) · 2024Article
- Rare variation in non-coding regions with evolutionary signatures contributes to autism spectrum disorder risk.Cell genomics · 2024Article
- Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedDatta, Vippan [corrected to Datta, Vipan]
Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
Single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor involved in the development and function of the paraventricular nucleus of the hypothalamus. Obesity has been reported in Sim1 haploinsufficient mice and in a patient with a balanced translocation disrupting SIM1. We sequenced the coding region of SIM1 in 2,100 patients with severe, early onset obesity and in 1,680 controls. Thirteen different heterozygous variants in SIM1 were identified in 28 unrelated severely obese patients. Nine of the 13 variants significantly reduced the ability of SIM1 to activate a SIM1-responsive reporter gene when studied in stably transfected cells coexpressing the heterodimeric partners of SIM1 (ARNT or ARNT2). SIM1 variants with reduced activity cosegregated with obesity in extended family studies with variable penetrance. We studied the phenotype of patients carrying variants that exhibited reduced activity in vitro. Variant carriers exhibited increased ad libitum food intake at a test meal, normal basal metabolic rate, and evidence of autonomic dysfunction. Eleven of the 13 probands had evidence of a neurobehavioral phenotype. The phenotypic similarities between patients with SIM1 deficiency and melanocortin 4 receptor (MC4R) deficiency suggest that some of the effects of SIM1 deficiency on energy homeostasis are mediated by altered melanocortin signaling.
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What OpenQuestion holds
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.