ArticleeLife2015
NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Pooled it
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- NKX2-5 Mutation and ICD Implantation in a Pregnant AV Block Patient.JACC. Case reports · 2025Article
- NKX2-5 congenital heart disease mutations show diverse loss and gain of epigenomic, biochemical and chromatin search functions underpinning pathogenicity.bioRxiv : the preprint server for biology · 2025Article
- Decoding congenital heart disease: a multi-omic framework for cardiac lineage and regulatory dysfunction.Frontiers in cell and developmental biology · 2025Review
- Galectins induced from hemocytes bridge phosphatidylserine and N-glycosylated Drpr/CED-1 receptor during dendrite pruning.Nature communications · 2024Article
- Pluripotent stem cells for target organ developmental toxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Review
- Modeling a variant of unknown significance in the Drosophila ortholog of the human cardiogenic gene NKX2.5.Disease models & mechanisms · 2023Article
- Article
- Disease-associated non-coding variants alter NKX2-5 DNA-binding affinity.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Activation of Nkx2.5 transcriptional program is required for adult myocardial repair.Nature communications · 2022Article
- Lack of food intake during shift work alters the heart transcriptome and leads to cardiac tissue fibrosis and inflammation in rats.BMC biology · 2022Article
- Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.Circulation · 2022Article
- Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article.Epigenetics insights · 2022Article
- A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease.Genome biology · 2021Article
- Advances in Cardiac Development and Regeneration Using Zebrafish as a Model System for High-Throughput Research.Journal of developmental biology · 2021Review
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Genetic and Epigenetic Control of Heart Development.Cold Spring Harbor perspectives in biology · 2020Review
- Identification of Target Genes and Transcription Factors in Mice with LMNA-Related Dilated Cardiomyopathy by Integrated Bioinformatic Analyses.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
Corrections and comments
- Commented on by
Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease.
Indexed as
Identifiers
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.