ArticleNature genetics2017
Estimating the selective effects of heterozygous protein-truncating variants from human exome data.
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 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
113 citing papers in PubMed, 193 citations in OpenAlex.
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Prediction of human missense variant effects from functional evidence.Nature genetics · 2026Article
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.PLoS genetics · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.bioRxiv : the preprint server for biology · 2026Article
- Regional nonsense constraint offers biological and clinical insights into genetic disease.Nature communications · 2026Article
- A scalable approach to resolving variants of uncertain significance.bioRxiv : the preprint server for biology · 2026Article
- The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects.Genome research · 2026Article
- IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy.Immunity · 2026Article
- Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes.bioRxiv : the preprint server for biology · 2025Article
- Spatial variation in the mutation rate within the plant shoot apical meristem.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Large-scale causal discovery using interventional data sheds light on gene network structure in k562 cells.Nature communications · 2025Article
- Functional Determinants and Evolutionary Consequences of Pleiotropy in Complex and Mendelian Traits.Molecular biology and evolution · 2025Article
- Estimation of demography and mutation rates from one million haploid genomes.American journal of human genetics · 2025Article
- Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations.Nature communications · 2025Article
- Reproductive and cognitive phenotypes in carriers of recessive pathogenic variants.Nature human behaviour · 2025Article
- A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects.PLoS genetics · 2025Article
- Insights from human NF-κB knockouts.EMBO reports · 2025Review
- A probabilistic graphical model for estimating selection coefficients of nonsynonymous variants from human population sequence data.Nature communications · 2025Article
- Socio-economic status is a social construct with heritable components and genetic consequences.Nature human behaviour · 2025Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
The evolutionary cost of gene loss is a central question in genetics and has been investigated in model organisms and human cell lines. In humans, tolerance of the loss of one or both functional copies of a gene is related to the gene's causal role in disease. However, estimates of the selection and dominance coefficients in humans have been elusive. Here we analyze exome sequence data from 60,706 individuals to make genome-wide estimates of selection against heterozygous loss of gene function. Using this distribution of selection coefficients for heterozygous protein-truncating variants (PTVs), we provide corresponding Bayesian estimates for individual genes. We find that genes under the strongest selection are enriched in embryonic lethal mouse knockouts, Mendelian disease-associated genes, and regulators of transcription. Screening by essentiality, we find a large set of genes under strong selection that are likely to have crucial functions but have not yet been thoroughly characterized.
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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.