ArticlePloS one2020
Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 19 citations in OpenAlex.
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Identifying and establishing the critical elements of a human cardiac in-vitro model for studying type-II diabetes.Discover applied sciences · 2025Article
- Four novel genetic mutations are associated with patent foramen ovale in Tibetan population using whole exome sequencing.Frontiers in genetics · 2025Article
- Of cells and tissues: Identifying the elements of a diabetic cardiac in vitro study model.Research square · 2024Article
- The genetic and molecular basis of a connexin-linked skin disease.The Biochemical journal · 2024Review
- Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer.Cancer science · 2024Article
- Cx31.1 can selectively intermix with co-expressed connexins to facilitate its assembly into gap junctions.Journal of cell science · 2024Article
- Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension.Journal of the American Heart Association · 2024Article
- Article
- Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.Nature cardiovascular research · 2023Article
- Connexinplexity: the spatial and temporal expression of connexin genes during vertebrate organogenesis.G3 (Bethesda, Md.) · 2022Article
- Serum-Induced Expression of Brain Natriuretic Peptide Contributes to Its Increase in Patients with HFpEF.International journal of molecular sciences · 2022Article
- Connecting different heart diseases through intercellular communication.Biology open · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions. This study investigated whether GJB4 plays an important role in human heart disease and function. METHODS AND
resultsWe examined a patient and her older brother who both presented with complicated severe hypertrophic cardiomyopathy (HCM) and whose parents are healthy married cousins. The gene exome analysis showed 340 single nucleotide polymorphisms (SNPs) that caused amino acid changes for which the patient was homozygous and both parents were heterozygous. After excluding all known common (>10%) SNP gene mutations, the gene for GJB4 was the only identified gene that is possibly associated with cardiac muscle. The resultant E204A substitution exists in the 4th transmembrane domain. GJB4-E204A impaired the binding with gap junction protein A1 (GJA1) compared with GJB4-WT. The expression of GJB4 was induced in rat disease models of left and right ventricle hypertrophy and mouse disease models of adriamycin-induced cardiomyopathy and myocardial infarction, while it was not detected at all in control. An immunohistochemical study was performed for autopsied human hearts and the explanted heart of the patient. GJB4 was expressed and colocalized with GJA1 in intercalated discs in human diseased hearts, which was extensively enhanced in the explanted heart of the patient. The abnormal expression and localization of GJB4 were observed in beating spheres of patient's induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). We generated knockout zebrafish of GJB4 by CRISPR/Cas9 and the endodiastolic volume and the ventricular ejection fraction were significantly lower in GJB4-deficient than in wild-type zebrafish at five days post-fertilization.
conclusionsThese results indicate both that GJB4 is defined as a new connexin in diseased hearts, of which mutation can cause a familial form of HCM, and that GJB4 may be a new target for the treatment of cardiac hypertrophy and dysfunction.
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