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更新于：2025-05-07

CASQ2

更新于：2025-05-07

基本信息

别名

calsequestrin 2、Calsequestrin-2、Calsequestrin, cardiac muscle isoform

+ [2]

简介

Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.

关联

项与 CASQ2 相关的药物

SGT-501

靶点

CASQ2 x RYR2

作用机制

CASQ2调节剂 [+1]

在研机构

Solid Biosciences, Inc.

原研机构

Solid Biosciences, Inc.

在研适应症

儿茶酚胺敏感性多形性室性心动过速

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

AT-307

靶点

CASQ2

作用机制

CASQ2调节剂

在研机构-

原研机构

Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabil

在研适应症-

非在研适应症

室性心动过速

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CASQ2 相关的临床结果

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100 项与 CASQ2 相关的转化医学

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0 项与 CASQ2 相关的专利（医药）

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321

项与 CASQ2 相关的文献（医药）

2025-03-01·Stem Cell Research

Generation of an isogenic CRISPR/Cas9-corrected control induced pluripotent stem cell line from a patient with autosomal dominant catecholaminergic polymorphic ventricular tachycardia with a heterozygous variant in cardiac calsequestrin-2

Article

作者: Li, Serena ; Lim, Seakcheng ; Semsarian, Christopher ; Holliday, Mira ; Ranpura, Ginell N ; Singer, Emma S ; Ross, Samantha B ; Bagnall, Richard D ; Fraser, Stuart T

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease characterised by adrenergic-induced arrhythmias. The leading causes of CPVT are pathogenic variants in cardiac ryanodine receptor 2 (RYR2) and rarely, in cardiac calsequestrin-2 (CASQ2) genes, which are major components of Ca²⁺ handling in cardiac myocytes. This resource builds upon an established induced pluripotent stem cell line generated from a family with autosomal dominant CPVT due to a heterozygous variant in CASQ2 c.539A > G, p.Lys180Arg (CIAUi003-A) (Ross et al., 2019). The current iPSC line was genetically modified using CRISPR/Cas9 to correct the pathogenic c.539A > G variant creating a CRISPR-corrected isogenic control line (CIAUi003-A-1).

2025-01-27·Journal of Cancer

Integrative multi-omics and machine learning identify a robust signature for discriminating prognosis and therapeutic targets in bladder cancer

Article

作者: Yang, Chadanfeng ; Li, Haihao ; Lv, Dihao ; Huang, Yinglong ; Wang, Haifeng ; Ding, Mingxia ; Gong, Chen ; Fu, Shi ; Wang, Jiansong ; Chen, Xiaorong ; Tan, Zhiyong

Background: Bladder cancer (BLCA) is a common malignant tumor whose pathogenesis has not yet been fully elucidated. This study analyzed prognostic genes in BLCA by integrating transcriptomics and proteomics data, and established prognostic models, aiming to offer novel insights for BLCA therapy. Methods: Transcriptomic, proteomic, and protein acetylation sequencing were conducted on six BLCA tumor tissues and six paraneoplastic tissue samples. Furthermore, data from TCGA-BLCA, GSE13507, and single-cell RNA sequencing (scRNA-seq) datasets were integrated. Initially, differential expression analysis identified candidate genes regulated by acetylation. These genes were further refined by intersecting with scRNA-DEG obtained from the scRNA-seq dataset, resulting in the identification of key genes. Subsequently, consistency clustering analysis was performed based on these key genes. Prognostic models were then developed utilizing Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. Independent prognostic factors were determined through independent prognostic analysis, followed by the establishment of a nomogram model. Additionally, gene set enrichment analysis (GSEA), immune cell infiltration analysis, mutation analysis, and drug sensitivity analysis were conducted between the two risk groups to elucidate underlying mechanisms. Results: A total of 15 key genes were obtained by crossing 284 candidate genes with 510 scRNA-DEGs. Patients in the TCGA-BLCA dataset were categorized into two subtypes based on the 15 key genes. Next, a risk model was developed using five prognostic genes (CTSE, XAGE2, MAP1A, CASQ2, and FXYD6), and a nomogram model was developed using age, pathologic T, pathologic N, and risk score. A total of 1089 GO entries and 49 KEGG pathways, including cytokine-cytokine receptor interactions, ECM receptor interactions, etc., were involved in all genes in both risk groups. The immunization score, matrix score, and ESTIMATE score were significantly higher in the low-risk group than in the high-risk group. Conclusion: CTSE, XAGE2, MAP1A, CASQ2 and FXYD6 were selected as prognostic genes in BLCA, risk model and nomogram model predicting the prognosis of BLCA patients were constructed. These were helpful for prognostic assessment of BLCA.

2024-12-01·Journal of Molecular and Cellular Cardiology Plus

Conditional ablation of MCU exacerbated cardiac pathology in a genetic arrhythmic model of CPVT

Article

作者: Gomez, Valeria ; Stewart, James A ; Hao, Jie ; Nguyen, Branden L ; Smuder, Ashley J ; Liu, Bin ; Deb, Arpita ; Knollmann, Bjorn C ; Tow, Brian D ; Wang, Ying

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmic syndrome caused by mutations in the calcium (Ca²⁺) release channel ryanodine receptor (RyR2) and its accessory proteins. These mutations make the channel leaky, resulting in Ca²⁺-dependent arrhythmias. Besides arrhythmias, CPVT hearts typically lack structural cardiac remodeling, a characteristic often observed in other cardiac conditions (heart failure, prediabetes) also marked by RyR2 leak. Recent studies suggest that mitochondria are able to accommodate more Ca²⁺ influx to inhibit arrhythmias in CPVT. Thus, we hypothesize that CPVT mitochondria can absorb diastolic Ca²⁺ to protect the heart from cardiac remodeling.Methods and resultsThe Mitochondrial Ca²⁺ uniporter (MCU), the main mitochondrial Ca²⁺ uptake protein, was conditionally knocked out in a CPVT model of calsequestrin 2 (CASQ2) KO. In vivo cardiac function was impaired in the CASQ2^-/--MCU^CKO model as assessed by echocardiography. Cardiac dilation and cellular hypertrophy were also observed in the CASQ2^-/--MCU^CKO hearts. Live-cell imaging identified altered Ca²⁺ handling and increased oxidative stress in CASQ2^-/--MCU^CKO myocytes. The activation status of Ca²⁺-dependent remodeling pathways (CaMKII, Calcineurin) was not altered in the CASQ2^-/--MCU^CKO model. RNAseq identified changes in the transcriptome of the CASQ2^-/--MCU^CKO hearts, distinct from the classic cardiac remodeling program of fetal gene re-expression.ConclusionsWe present genetic evidence that mitochondria play a protective role in CPVT. MCU-dependent Ca²⁺ uptake is crucial for preventing pathological cardiac remodeling in CPVT.

项与 CASQ2 相关的新闻（医药）

2023-11-09

·BioSpace

Solid Biosciences to Participate at Jefferies London Healthcare Conference

CHARLESTOWN, Mass., Nov. 09, 2023 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced that Bo Cumbo, President and Chief Executive Officer, will present at the Jefferies London Healthcare Conference on Wednesday, November 15, 2023, at 5:00 pm GMT. A live webcast of the presentation will be available on the Events page of the Investors section of the Company website or by clicking here. A webcast replay will be archived for 30 days on the Events page. Institutional investors interested in meeting with management during the conference may reach out to their Jefferies representatives. About Solid Biosciences Solid Biosciences is a life sciences company focused on advancing a portfolio of gene therapy candidates and neuromuscular and cardiac programs, including SGT-003, for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, AVB-202-TT for the treatment of Friedreich’s ataxia, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit . Solid Biosciences Contact: Leah Monteiro VP, Investor Relations & Communications 617-766-3430 lmonteiro@solidbio.com

基因疗法