ArticleEndocrinology2014
Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors.Pharmacogenetics and genomics · 2017Pooled it
- Monoallelic SH2B1 Variants in Neurodevelopmental Disorders: Phenotypic Expansion and Functional Characterization of Rare Variants.Molecular genetics & genomic medicine · 2026Article
- Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health.Molecular psychiatry · 2026Article
- Distribution of Variants and Identification of Novel Variants in Patients with Obesity Using Next-Generation Sequencing in Genes Associated with Obesity: A Single-Center Experience in Turkey.Molecular syndromology · 2025Article
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Identification of βIIΣ1-Spectrin as a Binding Partner of the GH-regulated Human Obesity Scaffold Protein SH2B1.Endocrinology · 2025Article
- Eating behavior patterns, metabolic parameters and circulating oxytocin levels in patients with obesity: an exploratory study.Eating and weight disorders : EWD · 2025Observational
- Endogenous SH2B1 protein localizes to lamellipodia and filopodia: platinum replica electron-microscopy study.microPublication biology · 2025Article
- SH2B1 Defends Against Energy Imbalance, Obesity, and Metabolic Disease via a Paraventricular Hypothalamus→Dorsal Raphe Nucleus Neurocircuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Oligogenic inheritance in severe adult obesity.International journal of obesity (2005) · 2024Article
- 2022 Cannon lecture: an ode to signal transduction: how the growth hormone pathway revealed insight into height, malignancy, and obesity.American journal of physiology. Endocrinology and metabolism · 2023Review
- Genetics and epigenetics in the obesity phenotyping scenario.Reviews in endocrine & metabolic disorders · 2023Review
- Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease.Cell reports. Medicine · 2023Article
- Role of the Beta and Gamma Isoforms of the Adapter Protein SH2B1 in Regulating Energy Balance.Endocrinology · 2023Article
- Genome Editing and Obesity.Advances in experimental medicine and biology · 2023Article
- The nucleolar δ isoform of adapter protein SH2B1 enhances morphological complexity and function of cultured neurons.Journal of cell science · 2022Article
- Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity.Diabetes · 2021Article
- High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Article
- Phenotypic and genetic analysis of an adult cohort with extreme obesity.International journal of obesity (2005) · 2019Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
We have previously reported rare variants in sarcoma (Src) homology 2 (SH2) B adaptor protein 1 (SH2B1) in individuals with obesity, insulin resistance, and maladaptive behavior. Here, we identify 4 additional SH2B1 variants by sequencing 500 individuals with severe early-onset obesity. SH2B1 has 4 alternatively spliced isoforms. One variant (T546A) lies within the N-terminal region common to all isoforms. As shown for past variants in this region, T546A impairs SH2B1β enhancement of nerve growth factor-induced neurite outgrowth, and the individual with the T546A variant exhibits mild developmental delay. The other 3 variants (A663V, V695M, and A723V) lie in the C-terminal tail of SH2B1α. SH2B1α variant carriers were hyperinsulinemic but did not exhibit the behavioral phenotype observed in individuals with SH2B1 variants that disrupt all isoforms. In in vitro assays, SH2B1α, like SH2B1β, enhances insulin- and leptin-induced insulin receptor substrate 2 (IRS2) phosphorylation and GH-induced cell motility. None of the variants affect SH2B1α enhancement of insulin- and leptin-induced IRS2 phosphorylation. However, T546A, A663V, and A723V all impair the ability of SH2B1α to enhance GH-induced cell motility. In contrast to SH2B1β, SH2B1α does not enhance nerve growth factor-induced neurite outgrowth. These studies suggest that genetic variants that disrupt isoforms other than SH2B1β may be functionally significant. Further studies are needed to understand the mechanism by which the individual isoforms regulate energy homeostasis and behavior.
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Registered trials
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