ArticleCell2020
Comprehensive In Vivo Interrogation Reveals Phenotypic Impact of Human Enhancer Variants.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
What it found
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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.
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Who cites it
116 citing papers in PubMed, 187 citations in OpenAlex.
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- Characterizing highly conserved fragments in 3'UTRs via statistical and transfer learning approaches.NAR genomics and bioinformatics · 2026Article
- Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo.Nature genetics · 2026Article
- Functional annotation of non-coding variants identifies a novel enhancer with activity in neural crest cell-derived lineages.Research square · 2026Article
- Precise, predictable genome integrations by deep-learning-assisted design of microhomology-based templates.Nature biotechnology · 2026Article
- Article
- Human promoter-driven AAV tools enable precision gene therapy targeting cochlear hair cells.Cell reports. Medicine · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Convergence of external and internal stressors on a stress-responsive enhancer of theProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Enhanced Expression of the Female-Biased Gene Gsta2 in Male Proximal Tubule Cells Improves Renal Resilience to Ischemia-Reperfusion Injury.Journal of the American Society of Nephrology : JASN · 2026Article
- Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity.Cell · 2026Article
- Predictive design of tissue-specific mammalian enhancers that functionbioRxiv : the preprint server for biology · 2025Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- A primordial germ cell-like-cell platform enables CRISPRi screen for epigenetic fertility modifiers.EMBO reports · 2025Article
- A DNA language model based on multispecies alignment predicts the effects of genome-wide variants.Nature biotechnology · 2025Article
- Data navigation on the ENCODE portal.Nature communications · 2025Article
- Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development.Nature ecology & evolution · 2025Article
- Redundant and Singular Regulatory Elements Underlie the Rapidly Evolving Pigmentation of Drosophila.Molecular biology and evolution · 2025Article
- Uncovering hidden enhancers through unbiased in vivo testing.Nature communications · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
Abstract
Establishing causal links between non-coding variants and human phenotypes is an increasing challenge. Here, we introduce a high-throughput mouse reporter assay for assessing the pathogenic potential of human enhancer variants in vivo and examine nearly a thousand variants in an enhancer repeatedly linked to polydactyly. We show that 71% of all rare non-coding variants previously proposed as causal lead to reporter gene expression in a pattern consistent with their pathogenic role. Variants observed to alter enhancer activity were further confirmed to cause polydactyly in knockin mice. We also used combinatorial and single-nucleotide mutagenesis to evaluate the in vivo impact of mutations affecting all positions of the enhancer and identified additional functional substitutions, including potentially pathogenic variants hitherto not observed in humans. Our results uncover the functional consequences of hundreds of mutations in a phenotype-associated enhancer and establish a widely applicable strategy for systematic in vivo evaluation of human enhancer variants.
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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.