ArticleBMC genomics2023
Small open reading frames: a comparative genetics approach to validation.
Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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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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
6 citing papers in PubMed, 9 citations in OpenAlex.
- Dark matter matters: from noncoding RNA regulation to cancer immunity.Oncoimmunology · 2026Review
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- High-resolution multi-omics enhances prediction and detection of smORF-encoded proteins in the human gut microbiome.Nature communications · 2026Article
- Mutational constraint analysis workflow for overlapping short open reading frames and genomic neighbors.BMC genomics · 2025Article
- ShortStop: a machine learning framework for microprotein discovery.BMC methods · 2025Article
- Molecular and functional characterization of the Drosophila melanogaster conserved smORFome.Cell reports · 2023Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Open reading frames (ORFs) with fewer than 100 codons are generally not annotated in genomes, although bona fide genes of that size are known. Newer biochemical studies have suggested that thousands of small protein-coding ORFs (smORFs) may exist in the human genome, but the true number and the biological significance of the micropeptides they encode remain uncertain. Here, we used a comparative genomics approach to identify high-confidence smORFs that are likely protein-coding. We identified 3,326 high-confidence smORFs using constraint within human populations and evolutionary conservation as additional lines of evidence. Next, we validated that, as a group, our high-confidence smORFs are conserved at the amino-acid level rather than merely residing in highly conserved non-coding regions. Finally, we found that high-confidence smORFs are enriched among disease-associated variants from GWAS. Overall, our results highlight that smORF-encoded peptides likely have important functional roles in human disease.
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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.