ArticleScience (New York, N.Y.)2012
A systematic survey of loss-of-function variants in human protein-coding genes.
Article in Science (New York, N.Y.), 2012. 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 748 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
748 citing papers in PubMed.
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- VN1K is a pangenome-informed multi-omics and phenomics resource for the Vietnamese population.Nature communications · 2026Article
- HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.bioRxiv : the preprint server for biology · 2026Article
- RankVar: machine learning-based variant ranking and reinterpretation for rare genetic diseases.Genome medicine · 2026Article
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- Targeting arginine metabolism reverses bone immunosuppressive microenvironment and metastasis in ARID1A-deficient triple negative breast cancer.Nature communications · 2026Article
- A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026Article
- Integrating common and rare variants improves polygenic risk prediction across diverse populations.Nature communications · 2026Article
- Functional insights into dispensable genes using genome-wide loss-of-function burden tests in Arabidopsis.The Plant cell · 2026Article
- Dissecting pleiotropy to gain mechanistic insights into human disease.Nature reviews. Genetics · 2026Review
- FAM96A functions as a novel pace controller for iron uptake to maintain iron homeostasis and erythropoiesis.Cell death and differentiation · 2026Article
688 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
52 authors.
Funding
Abstract
Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.
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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.