Ask about this productRelated genes to: TOM1L2 antibody
- Gene:
- TOM1L2 NIH gene
- Name:
- target of myb1 like 2 membrane trafficking protein
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-16
- Date modifiied:
- 2015-09-08
Related products to: TOM1L2 antibody
Related articles to: TOM1L2 antibody
- Osteoporosis is a highly heritable metabolic bone disorder characterized by low bone mass and increased fracture risk. However, the causal genes underlying disease susceptibility remain incompletely understood. In this study, we employed a summary-data-based Mendelian randomization (SMR) framework to identify genes with potential causal effects on osteoporosis by integrating genome-wide association study summary statistics from the FinnGen consortium with multilayer molecular quantitative trait loci (xQTL) data, including expression, splicing, methylation, and protein QTLs across multiple tissues (106 xQTL datasets in total). The heterogeneity in dependent instruments (HEIDI) test was applied to distinguish pleiotropic associations from linkage disequilibrium-driven effects. Functional characterization was further conducted using Gene Ontology and KEGG pathway enrichment analyses, protein-protein interaction network construction, drug-gene enrichment analysis, and molecular docking. Using this integrative approach, we identified 15 high-confidence genes - CEP112, CKB, GID4, MEOX1, MEPE, PPP6R3, RGS9, RSPO3, SERPINA1, SFRP4, SOST, SPP1, SREBF1, TOM1L2, and ZBTB48 - showing evidence of causal associations with osteoporosis after stringent multiple-testing correction and HEIDI filtering. These genes included established regulators of bone metabolism as well as novel candidates involved in metabolic regulation and signal transduction. Enrichment analyses highlighted pathways related to Wnt and bone morphogenetic protein signaling, extracellular matrix organization, and metabolic processes, while network analysis revealed substantial functional connectivity among the prioritized genes. In addition, drug-gene enrichment analysis prioritized β-carotene, apocarotenal, and bezafibrate as potential therapeutic candidates, with molecular docking supporting stable interactions with key protein targets. Overall, this study provides robust genetic evidence for causal molecular regulators of osteoporosis and highlights potential therapeutic targets, offering a clinically relevant resource for future functional validation and translational research. - Source: PubMed
Yu FeiWan XiwenQiu Jiaxuan - Intracellular signaling pathways are modulated by ubiquitin-dependent trafficking, in which specific plasma membrane receptors and cytosolic proteins are tagged, internalized, and degraded in the endolysosomal pathway. Target of Myb1 (TOM1) family proteins, including TOM1, TOM1-L1, and TOM1-L2 function as early adaptors within the ESCRT-0 machinery to recognize ubiquitinated cargo and coordinate its sorting. TOM1 proteins interact with ubiquitin and accessory proteins, such as TOLLIP, facilitating efficient cargo sequestration and endosomal maturation. These interactions are known to be modulated by pathogen-driven processes, such as Shigella flexneri-mediated phosphatidylinositol 5-phosphate accumulation, which can impair TOM1-dependent cargo trafficking. Beyond endosomal sorting, TOM1 contributes to autophagic flux by linking autophagosomes and endosomes through its interaction with the motor protein Myosin VI. Dysregulation of these pathways has been implicated in immune disorders, myocardial ischemia-reperfusion injury, and potentially tumorigenesis. In plants, TOM1-like proteins serve as functional ESCRT-0 analogs, mediating ubiquitin-dependent cargo sorting and integrating stress-responsive signaling. Recent studies have shed light on the modular organization of TOM1, revealing mechanisms of ubiquitin recognition, DXXLL motif function, and complex formation with adaptor proteins. Nonetheless, key questions remain regarding how TOM1 discriminates among ubiquitin linkages, interacts with distinct phosphoinositides under varying physiological conditions, and cooperates with TOLLIP during selective autophagy. Elucidating these mechanisms will advance our understanding of cellular transport and signaling and may reveal novel intervention targets for inflammatory and autoimmune diseases in humans as well as for improving drought tolerance and immune regulation in plants. - Source: PubMed
Publication date: 2026/05/26
Collins Megan VLång Heljä K MFinkielstein Carla VRyhänen Samppa JIkonen ElinaCapelluto Daniel G S - Histone deacetylases (HDACs) play critical roles in immune regulation and inflammatory responses in sepsis. This study identified HDAC-related genes and explored their potential roles in sepsis. - Source: PubMed
Publication date: 2026/04/06
Wang YuanyuanShu TaoLi YanpengKang QiangqiangJia ZhanshengMa Chunyan - Mitochondrial dysfunction is a central driver of irreversible neuronal injury following ischemic stroke (IS); yet effective strategies to restore mitochondrial function and promote long-term neurological recovery remain limited. In this study, we demonstrate that mitochondrial extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSC Mito-EVs) serve as a novel biotherapeutic vehicle capable of delivering functional mitochondria to damaged neurons. This process involves Target of Myb1-like 2 membrane trafficking protein (Tom1l2)-dependent membrane fusion between hUCMSC Mito-EVs and neuronal mitochondria, leading to the restoration of mitochondrial membrane potential and mitochondrial function. Mechanistically, Mito-EVs-mediated mitochondrial transfer upregulates cardiolipin synthase 1 (CRLS1), which preserves the inner mitochondrial membrane integrity and stabilizes respiratory chain complexes. The restoration of mitochondrial structure and function subsequently reduces reactive oxygen species production, suppresses pyroptosis, and promotes the recovery of neuronal metabolic and functional homeostasis. Collectively, these findings suggest that the Tom1l2-Crls1 axis serves as a key mediator of mitochondrial repair in hUCMSC Mito-EVs therapy, highlighting its promising potential as a targeted therapeutic strategy for neuronal protection following IS. - Source: PubMed
Publication date: 2026/03/02
Li ZihengZhu XingjiaLiao WeiquanJiang RuiSang EnzeZhu JueSun GaojiaLu ZhichaoWang ChenxingJiang YiChen JianGong PeipeiLiu Qianqian - Genome-Wide Association Studies (GWAS) have transformed human genetics by identifying thousands of loci associated with complex traits and diseases. Yet, individual GWAS are often underpowered, and traditional meta-analysis methods - though widely used in tools such as METAL, GWAMA, and PLINK- typically analyze one trait at a time. This univariate focus risks overlooking pleiotropy and the correlations among traits that underlie complex genetic architectures. To address this gap, we introduce fastMETA, a novel and computationally efficient framework for multivariate meta-analysis of GWAS summary statistics. fastMETA implements an adaptation of the marginal method of moments (MmoM), avoiding the computational burden of hierarchical multivariate models while retaining statistical rigor. Three estimation strategies are provided: (i) a direct replication of the classical MmoM, (ii) a Pearson correlation-based approach, and (iii) a new method that aggregates correlations across all SNPs to estimate a stable trait correlation matrix. This last approach is particularly suited to large-scale GWAS, where within-study correlations are rarely available. We benchmarked fastMETA against existing multivariate meta-analysis packages (mvmeta in R and Stata, xmeta in R) using both real and synthetic datasets. Across scenarios, fastMETA consistently achieved 15-20× faster runtimes while maintaining high concordance with established methods. Applications included: (a) a bivariate meta-analysis of pediatric musculoskeletal traits, replicating pleiotropic effects at the TOM1L2/SREBF1 locus; (b) a multivariate meta-analysis of inflammatory bowel disease gene-expression data, showing near-identical results to published findings; and (c) a large set of genetic association meta-analyses, demonstrating robustness even when within-study correlations were ignored. By combining speed, robustness, and flexibility, fastMETA enables researchers to efficiently explore pleiotropy and complex trait relationships in modern GWAS. Its open-source Python implementation is available both as a standalone tool and as a web service (https://github.com/pbagos/fastMETA), lowering barriers to adoption. Importantly, fastMETA provides a practical and scalable solution for the next-generation of genomic meta-analyses, supporting deeper insights into the genetic basis of multifactorial diseases. - Source: PubMed
Publication date: 2025/12/19
Manios Georgios AKandylas DionysiosKylonis AthanasiosBagos Pantelis GKontou Panagiota I