Ask about this productRelated genes to: LDB3 Blocking Peptide
- Gene:
- LDB3 NIH gene
- Name:
- LIM domain binding 3
- Previous symbol:
- CMD1C
- Synonyms:
- PDLIM6, KIAA0613, ZASP
- Chromosome:
- 10q23.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-12-04
- Date modifiied:
- 2019-04-23
Related products to: LDB3 Blocking Peptide
Related articles to: LDB3 Blocking Peptide
- Dilated cardiomyopathy (DCM), a progressive cardiac disorder marked by ventricular dilatation and systolic dysfunction, involves a complex interplay between genetic and immune dysregulation. However, how alternative splicing remodeling contributes to its molecular heterogeneity remains poorly understood. Here, we performed an integrated transcriptomic analysis to characterize DCM-associated alternative splicing landscapes and their regulation by splicing factor networks. We identified widespread differential alternative splicing (DAS) events in DCM, with affected genes significantly enriched in cardiac contraction, sarcomere organization, calcium handling, extracellular matrix remodeling, and protein metabolism. Representative splicing events in key cardiac genes, including , , , and , exhibited distinct junction usage and percent spliced in (PSI) alterations between DCM and control samples, suggesting functionally relevant transcript isoform remodeling. By integrating splicing factor expression profiles with DAS event PSI values, we constructed a characteristic SF-AS regulatory network and identified five key splicing factors-, , , , and -as candidate tissue-level biomarkers of DCM-associated splicing remodeling. Molecular subtype analysis further revealed distinct DCM subgroups characterized by divergent immune infiltration patterns, pathway activities, and hub gene signatures. Machine learning-based identification and external validation supported the diagnostic potential of this five-splicing-factor signature. Collectively, this study deciphers coordinated splicing factor-associated alternative splicing remodeling in DCM, providing deeper insights into the immune-associated molecular heterogeneity and potential regulatory mechanisms underlying disease progression. - Source: PubMed
Publication date: 2026/09/04
Li JiaHe YiyuZhao XianxianGuo ZhifuSong JinchaoSong Xiaowei - Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource evaluation, the DCM gene curation expert panel reconvened in 2024-2025 to conduct a reassessment of genes in DCM. - Source: PubMed
Publication date: 2026/09/08
Jordan ElizabethGrover PhoenixParker PatriciaCowan JasonAsatryan BabkenAi TomohikoBerthold AkosBronicki LucasBrown EmilyCeleghin RudyEdwards MatthewFan JudithJames Cynthia AJohnson ReneeJudge Daniel PJurgens SeanLahrouchi NajimLumbers TomMazzarotto FrancescoMedeiros Domingo ArgeliaMurray BrittneyPeters StaceyPilichou KalliopiProtonotarios Alexandrosvan Spaendonck-Zwarts KarinSyrris PetrosWang JessicaWalsh RoddyWare James SHershberger Ray E - The scaffolding protein Zasp52 is required to maintain structure at the muscle Z-disc, which experiences strong forces during contraction. It is alternatively spliced into many isoforms, some of which contain a long intrinsically disordered region (IDR). We show that this region is primarily expressed in the indirect flight muscle (IFM) and is required for maintaining the integrity of the Z-disc. Deleting the IDR-encoding exon 15e results in flightlessness and structural IFM defects, including sarcomere bending at the Z-disc and an inability to de-contract. These defects are indicative of a lack of proper thin filament anchoring to the Z-disc. This is further supported by a genetic interaction between exon 15e and actin. Fluorescence recovery after photobleaching of an isoform lacking exon 15e shows that the IDR is required for maintaining Zasp52 at the Z-disc and thereby stabilizing Z-discs. Lastly, we can rescue these phenotypes by restricting IFM use. Together, these results suggest that Zasp52's IDR confers thin filament stability at the Z-disc of IFM. - Source: PubMed
Publication date: 2026/08/27
Ho NikolaiSchöck Frieder - The autosomal dominant p.Ala165Val mutation in LIM Domain Binding Protein 3 (LDB3) causes myofibrillar myopathy marked by Z-disc disruption, accumulation of filamin-C (FLNc) and chaperone proteins, and progressive muscle weakness. We previously showed that this mutation interferes with the LDB3-protein kinase C alpha (PKCα)-FLNc mechanosensing axis and impairs chaperone-assisted selective autophagy (CASA), establishing a gain-of-function mechanism. In this study, we examined whether mutant allele-specific knockdown could reverse the disease or mitigate disease progression . A single intramuscular-injection of an AAV9-delivered microRNA-based shRNA produced substantial knockdown of mutant transcripts and protein in knock-in mice treated either before or after the onset of pathology. Treatment after disease onset reduced filamin-C and CASA protein aggregates and improved muscle strength, whereas early intervention prevented development of molecular and histological features of myopathy. Phosphoproteomic profiling further showed broad remodeling of dysregulated phosphorylation networks, including restoration of PKCα-responsive sites and normalization of altered sarcomeric and cytoskeletal signaling observed in mice. These findings identify disruption of the LDB3-PKCα-FLNc mechanosensing pathway as a central disease driver and suggest that restoring this signaling axis may complement mutant allele-specific RNA interference (RNAi). Overall, our results support RNAi as a promising therapeutic strategy for dominant LDB3-related myofibrillar myopathy. - Source: PubMed
Publication date: 2026/03/31
Pathak PankajPalmeri JessicaHale JessicaSabu-Kurian AnnaPeiravi MortezaSpringer Danielle ALi YanJohnson Kory RMankodi Ami - : Cardiomyocyte-derived small extracellular vesicles (CM-sEVs) have emerged as important mediators of intercellular communication in cardiovascular diseases (CVDs). However, their origin-tracing markers, molecular signatures, and clinical applications remain incompletely characterized and lack systematic synthesis. This systematic review aimed to comprehensively evaluate CM-sEVs-specific markers, disease-associated cargos alterations, and their roles in intercellular communication. - Source: PubMed
Publication date: 2026/05/18
Liu ShaojiaoTeng YuSu ShaWang MengWang LeiZhao Mingjing