ArticlePLoS biology2023
Functional unknomics: Systematic screening of conserved genes of unknown function.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed.
- The microbial unknome, a repertoire for microbial chatting?Heredity · 2026Review
- Progressive Slurred Speech as an Atypical Presentation of GDAP2-Related Spinocerebellar Ataxia: A Case Report.Cureus · 2026Article
- GATSBI: improving context-aware protein embeddings through biologically motivated data splits.Bioinformatics (Oxford, England) · 2026Article
- The role ofBlood science (Baltimore, Md.) · 2026Article
- Enzymology of the metazoan tRNA ligase complex: a lifetime in cycles.Cellular and molecular life sciences : CMLS · 2026Review
- GATSBI: Improving context-aware protein embeddings through biologically motivated data splits.bioRxiv : the preprint server for biology · 2026Article
- Cosmopolitan Gene Families With Known Functions Are Hotspots for the Evolution of Novel Genes in Stony Corals.Genome biology and evolution · 2026Article
- A Beginner's How-To Guide to Urban Population Genetics and Genomics.Ecology and evolution · 2026Review
- A machine learning classifier to identify and prioritise genes associated with murine cardiac development.PLoS genetics · 2026Article
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- CysDuF database: annotation and characterization of cysteine residues in domain of unknown function proteins based on cysteine post-translational modifications, their protein microenvironments, biochemical pathways, taxonomy, and diseases.Database : the journal of biological databases and curation · 2026Article
- Functional annotation of novel heat stress-responsive genes in rice utilizing public transcriptomes and structurome.Bioinformatics advances · 2026Article
- Beyond sequence similarity: toward function-based screening of nucleic acid synthesis.Frontiers in bioengineering and biotechnology · 2026Article
- InspectorORF: a tool for visualizing Ribo-Seq and additional genomic or transcriptomic data.Bioinformatics advances · 2026Article
- Proteome-widebioRxiv : the preprint server for biology · 2025Article
- Predicting protein-protein interactions in the human proteome.Science (New York, N.Y.) · 2025Article
- Limitations of current machine learning models in predicting enzymatic functions for uncharacterized proteins.G3 (Bethesda, Md.) · 2025Article
- Creation and validation of a proteome-wide yeast library for protein detection and analysis.Journal of cell science · 2025Article
- The Case for Limiting "Sequences of Concern" to Those with Demonstrated Pathogenic Function.Applied biosafety : journal of the American Biological Safety Association · 2025Article
- Phenotype to genotype: A new and rapid approach using whole-genome sequencing.PLoS genetics · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
The human genome encodes approximately 20,000 proteins, many still uncharacterised. It has become clear that scientific research tends to focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed a publicly available and customisable "Unknome database" that ranks proteins based on how little is known about them. We applied RNA interference (RNAi) in Drosophila to 260 unknown genes that are conserved between flies and humans. Knockdown of some genes resulted in loss of viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control, and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and 2 genes contributing to male fertility. Our work illustrates the importance of poorly understood genes, provides a resource to accelerate future research, and highlights a need to support database curation to ensure that misannotation does not erode our awareness of our own ignorance.
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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.