Ask about this productRelated genes to: SIM1 Blocking Peptide
- Gene:
- SIM1 NIH gene
- Name:
- SIM bHLH transcription factor 1
- Previous symbol:
- -
- Synonyms:
- bHLHe14
- Chromosome:
- 6q16.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-22
- Date modifiied:
- 2018-04-20
Related products to: SIM1 Blocking Peptide
Related articles to: SIM1 Blocking Peptide
- Recently, functional evaluation using 3D gait analysis (3DGA) proved to predict health-related quality-of-life (HRQOL) scores better than static radiographic evaluation in adult spinal deformity (ASD). However, 3DGA provides multiple parameters that can be a burden to interpret by non-experts. A recent study showed that the dynamic pelvic tilt (dPT), the forward projection of the head and thorax (dODHA) and walking step length (SL) are the most representative gait kinematics in ASD patients. - Source: PubMed
Publication date: 2026/04/28
Mekhael ElioRachkidi RamiNassim NabilHaddad Georges ElBoutros MarcKaram Maria RWakim EmmanuelleAsmar MariaKaram MohamadMassaad AbirGhanem IsmatAssi Ayman - Genetic factors are key determinants in the pathophysiology of obesity, regulating energy homeostasis. Monogenic non-syndromic obesity accounts for 2-3% of obesity in both children and adults and is most often attributable to mutations in genes encoding components of the leptin-melanocortin pathway. Genetic testing is indicated in children with severe obesity before age 5, hyperphagia, a family history of obesity, and neurodevelopmental delay or organ dysfunction. Mutations associated with monogenic obesity follow autosomal recessive (, , , and ) or autosomal dominant (, , , ) modes of inheritance. Other gene mutations in heterozygous states (, , , ) are associated with obesity and may exhibit autosomal dominant inheritance; however, the clinical phenotype depends on the degree of genetic penetrance and interactions with other genetic and/or environmental factors. No approved targeted pharmacotherapies are currently available for autosomal dominant monogenic obesity, and the frequent detection of variants of uncertain significance often hinders timely diagnostic confirmation. The review provides a comprehensive appraisal of autosomal dominant forms of monogenic non-syndromic obesity, analyzing genetic and molecular features, clinical presentations, and therapeutic strategies. - Source: PubMed
Publication date: 2026/02/01
Luppino GiovanniGiordano MaraFranchina FrancescaCoco RobertoInì EleonoraFazio CarlaPorri DeboraLugarà CeciliaCorica DomenicoAversa TommasoWasniewska Malgorzata - The paraventricular hypothalamus (PVH) controls behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for centrally projecting PVH neuron populations remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to catalog PVH neuron subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to map them spatially. Our spatial transcriptomic atlas resolves 26 Sim1 and 29 GABAergic neuron populations from the PVH and surrounding areas. Additionally, projection-based profiling identified neurons that project to the parabrachial region (PB) and spinal cord, helping to determine PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, activation of PB-projecting PVH neurons expressing Brs3 reduces food intake, and silencing them causes obesity. Together, this atlas contributes high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis. - Source: PubMed
Publication date: 2026/01/23
Li YuxiButler Trevor CNardone StefanoJacobs Christopher LDouglass Amelia MMadara Joseph CMcDonough Miriam CTao JenkangLowenstein Elijah DWang LuhongPant DeeptiWalker Samuel JWang AnnetteSrinivasan HariniYang ZongfangCampbell John NTsai Linus TLowell Bradford BResch Jon M - Monogenic forms of severe early-onset obesity often involve genetic disruptions in the hypothalamic leptin-melanocortin pathway. Pathogenic variants in the gene, a key transcription factor required for the development of the paraventricular nucleus, are a known cause of Prader-Willi-like syndrome, characterized by hyperphagia, severe obesity, and developmental delay. We performed targeted next-generation sequencing of 52 obesity-associated genes on a cohort of pediatric patients with severe early-onset obesity. Identified variants were analyzed for population frequency and predicted pathogenicity using in silico tools. The structural impact of the novel missense variants was assessed using protein domain modeling with AlphaFold3. We identified five rare variants in eleven patients. Four were heterozygous nonsynonymous variants: one frameshift in the bHLH domain (p.Ser18Ter), one frameshift in the Per-ARNT-Sim domain (p.His143Ter), and two missense variants, p.Pro30Ala and p.Ser663Leu. Structural modeling suggested that the missense variants are likely to disrupt critical protein-protein interactions. The fifth variant was a synonymous change, c.1173G>A, p.(Ser391Ser), which was detected in five unrelated patients. Bioinformatic analysis predicted that this variant could alter splicing. Structural modeling suggested that the missense variants interfere with SIM1 function. This study expands the mutational spectrum of SIM1-linked monogenic obesity, reporting novel likely pathogenic frameshift variants, a missense variant, and a recurrent synonymous variant with a potential splice-site effect. The majority of the variants are predicted to affect the SIM1 protein. Our findings strengthen the critical role of the gene in hypothalamic development and energy homeostasis. The results underscore the importance of including the gene in genetic testing panels for children with severe obesity and hyperphagia, enabling precise diagnosis and potential future personalized management. Functional in vitro or in vivo validation of these variants is required to confirm their pathogenicity. - Source: PubMed
Publication date: 2026/01/05
Mohammed IdrisAhmed Wesam SAl-Barazenji TaraDauleh HajarLove Donald RHussain Khalid - The basic-helix-loop-helix Per-Arnt-Sim (PAS) homology domain (bHLH-PAS) transcription factor (TF) family comprises critical sensors or actuators of physiological (hypoxia, tryptophan metabolites, neuronal activity, and appetite) and environmental (diet-derived metabolites and pollutants) stimuli regulating genes involved in signal adaptation and homeostasis. Despite the importance of this TF family, the mechanisms underlying specificity of DNA binding and target gene regulation by the bHLH-PAS subfamily remain unresolved. We systematically analysed cognate DNA binding hierarchies of prototypical bHLH-PAS family members (ARNT, ARNT2, HIF1α, HIF2α, AhR, NPAS4, SIM1), revealing large DNA binding footprints (12-15 bp) and unique mechanisms of DNA binding specificity involving preferential DNA sequences flanking the core motif. Flank-encoded DNA binding specificity discerns otherwise identical core sequence binding by SIM1 and the HIFs, mediated through N-terminal HIFα-DNA interactions. We also reveal an intimate relationship between DNA shape and core and flank TF binding that allows motif sequence flexibility and underpins multimodal mechanisms for achieving TF binding specificity. Furthermore, novel downstream SIM1 PAS-loop/DNA interactions are associated with AT-rich sequences contributing to DNA binding and transcriptional activity; these interactions are critical for TF biological function underpinning a monogenic cause of human hyperphagic obesity in a recapitulated SIM1.R171H knock-in mouse model. - Source: PubMed
Bersten David CMcDougal Daniel PSullivan Adrienne EGerassimou AlexisBreen JamesFitzsimmons Rebecca LMuscat George E OPederson StephenBruning John BFan Chen-MingThomas Paul QRussell Darryl LPeet Daniel JWhitelaw Murray L