ArticleCardiovascular research2014
NEXN inhibits GATA4 and leads to atrial septal defects in mice and humans.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pooled it
- Genetic and Phenotypic Characterization of Nexilin (NEXN)-Related Cardiomyopathy: Results From a Multicentric Study.JACC. Heart failure · 2025Article
- The Role of miRNA Expression in Congenital Heart Disease: Insights into the Mechanisms and Biomarker Potential.Children (Basel, Switzerland) · 2025Review
- Transposition of the Great Arteries With Intact Ventricular Septum and Fetal-Onset Dilated Cardiomyopathy in a Neonate With a Homozygous NEXN Variant.Case reports in pediatrics · 2025Article
- Article
- Article
- Nexilin in cardiomyopathy: unveiling its diverse roles with special focus on endocardial fibroelastosis.Heart failure reviews · 2024Review
- Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I.International journal of molecular sciences · 2024Review
- Transcriptome studies of congenital heart diseases: identifying current gaps and therapeutic frontiers.Frontiers in genetics · 2023Review
- Loss of Nexilin function leads to a recessive lethal fetal cardiomyopathy characterized by cardiomegaly and endocardial fibroelastosis.American journal of medical genetics. Part A · 2022Article
- Two genetic variants inFrontiers in cardiovascular medicine · 2022Article
- Identification of LTF as a Prognostic Biomarker for Osteosarcoma.Journal of oncology · 2022Article
- Association between single-nucleotide polymorphisms ofOpen life sciences · 2022Article
- Single-cell RNA sequencing analysis to characterize cells and gene expression landscapes in atrial septal defect.Journal of cellular and molecular medicine · 2021Article
- GATA2 regulates the CAD susceptibility gene ADTRP rs6903956 through preferential interaction with the G allele.Molecular genetics and genomics : MGG · 2021Article
- Identification and functional study of GATA4 gene regulatory variants in atrial septal defects.BMC cardiovascular disorders · 2021Article
- Genetics of Congenital Heart Disease.Biomolecules · 2019Review
- Translating emerging molecular genetic insights into clinical practice in inherited cardiomyopathies.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Across-Experiment Transcriptomics of Sheep Rumen Identifies Expression of Lipid/Oxo-Acid Metabolism and Muscle Cell Junction Genes Associated With Variation in Methane-Related Phenotypes.Frontiers in genetics · 2018Article
- Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
26 authors at 12 institutions in 2 countries.
Funding
Abstract
aimsCardiac structural genes have been implicated as causative factors for congenital heart diseases (CHDs). NEXN is an F-actin binding protein and previously identified as a disease gene causing cardiomyopathies. Whether NEXN contributes to CHDs aetiologically remains unknown. Here, we explored the function of NEXN in cardiac development. METHODS AND
resultsFirst, we determine the role of NEXN in cardiac differentiation using mouse P19cl6 in vitro model; we demonstrated that NEXN inhibited cardiac contractile markers, serving as a negative regulator. Interestingly, we found this effect was mediated by GATA4, a crucial transcription factor that controls cardiac development by knockdown, overexpression, and rescue experiment, respectively. We then generated transgenic mouse models and surprisingly, we discovered cardiac-selective expression of the NEXN gene caused atrial septal defects (ASDs). Next, to search for the mutations in NEXN gene in patients suffering from ASDs, we sequenced the exon and exon-intron joint regions of the NEXN gene in 150 probands with isolated ASDs and identified three mutations in the conserved region of NEXN (c.-52-78C>A, K199E, and L227S), which were not found in 500 healthy controls. Finally, we characterize the related mechanisms and found all mutations inhibited GATA4 expression.
conclusionWe identify NEXN as a novel gene for ASD and its function to inhibit GATA4 established a critical regulation of an F-actin binding protein on a transcription factor in cardiac development.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.