ArticleNature communications2020
Characterising the loss-of-function impact of 5' untranslated region variants in 15,708 individuals.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 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.
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.
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Who cites it
117 citing papers in PubMed, 189 citations in OpenAlex.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- Site-specific inhibition of translation initiation via 2'-O-methylation.Nucleic acids research · 2026Article
- Incremental yield of genome sequencing after exome sequencing for nonimmune hydrops fetalis spectrum.American journal of obstetrics & gynecology MFM · 2026Article
- Overlapping upstream ORFs repress translation and expand proteome diversity in Arabidopsis.bioRxiv : the preprint server for biology · 2026Article
- Article
- Identification of 5' untranslated region variants in genes involved in neurodevelopmental disorders.Journal of human genetics · 2026Article
- Human SRD5A1 as a case of gene expression indel-resistance in triple-coding region.Genome biology · 2026Article
- CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.Science China. Life sciences · 2026Article
- 5' UTR length shapes alternative N-terminal protein isoforms across cancers and in rare disease.EMBO reports · 2026Article
- Pharmacogenomics of Major Depressive Disorder in Indigenous Amazonian Populations.Clinical pharmacology and therapeutics · 2026Article
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes.American journal of human genetics · 2026Article
- The birth, death, and evolutionary compensation of uORFs in Drosophila.Nucleic acids research · 2026Article
- An expanded reference catalog of translated open reading frames for biomedical research.Nucleic acids research · 2026Article
- Novel genetic and nerve imaging characterization of Charcot-Marie-Tooth disease type 4F.Neurogenetics · 2026Article
- 5' UTR length regulates alternative N-terminal protein isoform production in health and disease.bioRxiv : the preprint server for biology · 2026Article
- A rare 5'UTR variant in SEC24D reveals translational dysfunction in osteogenesis imperfecta: a roadmap for RNA therapeutic rescue.Scientific reports · 2026Article
- Discovering, Integrating, and Reinterpreting the Molecular Logic of Life: From Classical Theories of Heredity to an Extended Functional Perspective on the Central Dogma.Life (Basel, Switzerland) · 2026Review
- Precision engineering of upstream open reading frames for translational regulation and crop improvement.Frontiers in genome editing · 2026Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
19 authors at 20 institutions in 18 countries.
Funding
Abstract
Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants that create or disrupt uORFs can cause disease. Here, in a systematic genome-wide study using 15,708 whole genome sequences, we show that variants that create new upstream start codons, and variants disrupting stop sites of existing uORFs, are under strong negative selection. This selection signal is significantly stronger for variants arising upstream of genes intolerant to loss-of-function variants. Furthermore, variants creating uORFs that overlap the coding sequence show signals of selection equivalent to coding missense variants. Finally, we identify specific genes where modification of uORFs likely represents an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in neurofibromatosis. Our results highlight uORF-perturbing variants as an under-recognised functional class that contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data in studying non-coding variant classes.
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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.