ArticleNature2020
Transcript expression-aware annotation improves rare variant interpretation.
Erratum issuedOpen access · hybridAbstract read
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Article in Nature, 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 131 papers.
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131citing papers in PubMed
26.8field-weighted citation impact, top 1% of its field
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Who cites it
131 citing papers in PubMed, 200 citations in OpenAlex.
- The novel transcripts we keep rediscovering.Nature biotechnology · 2026Article
- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Long-read RNA-seq maps the isoform landscape of the trigeminal ganglion in an allergic rhinitis mouse model.BMC genomics · 2026Article
- A Comprehensive Analysis of the Agreement and Performance of Variant Annotation Programs in Equine Genomes.Genes · 2026Article
- Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms.Nature communications · 2026Article
- Reclassification ofBiomolecules & biomedicine · 2026Article
- LongAllele: a joint inference framework for allele-specific analysis on long-read bulk and single-cell RNA sequencing.bioRxiv : the preprint server for biology · 2026Article
- Tissue-specific gene dosage disruption is a key feature and pathogenic mechanism of structural variants in the human genome.Genome medicine · 2026Article
- Interstitial cystitis: a phenotype and rare variant exome sequencing study.EBioMedicine · 2026Article
- Genotype-Phenotype Correlations in Pediatric Hereditary Pancreatitis: Evidence from a Romanian Retrospective Cohort.Journal of clinical medicine · 2026Article
- Regional nonsense constraint offers biological and clinical insights into genetic disease.Nature communications · 2026Article
- A recently evolved TAF8 isoform arising from anbioRxiv : the preprint server for biology · 2026Article
- Interpretable machine-learning prediction of PSEN1 missense variant pathogenicity based on multi-omics enrichment in six core Alzheimer's disease genes.Alzheimer's research & therapy · 2026Article
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- Identification of Novel Pathogenic Variants in Familial Adenomatous Polyposis Through Whole Genome Sequencing.Human mutation · 2026Article
- Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes.bioRxiv : the preprint server for biology · 2025Article
- To be or not to be a protein coding mutation, that's the question!NAR genomics and bioinformatics · 2025Review
- Integrative and accurate annotations enhance current nonsense-mediated mRNA decay rules.Nucleic acids research · 2025Article
- Analysis of Transcript Expression and Core Promoter DNA Sequences of Brain, Adipose Tissues and Testis in Human and Fruit Fly.International journal of molecular sciences · 2025Article
- Reply to: 'Predicted loss-of-function variants before Met584 in ARID1B in population cohorts likely reflect reduced penetrance and should be reported diagnostically'.Genome medicine · 2025Article
71 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 20 institutions in 17 countries.
Beryl B CummingsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6346-1646
Konrad J KarczewskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2878-4671
Jack A KosmickiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eleanor G SeabyProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas A WattsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Moriel Singer-BerkProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jonathan M MudgeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Juha KarjalainenProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
F Kyle SatterstromProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6187-7680
Anne H O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6418-9592
Timothy PoterbaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cotton SeedAnalytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Matthew SolomonsonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jessica AlföldiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9713-6200
Genome Aggregation Database Production Team
Genome Aggregation Database Consortium
Mark J DalyProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0949-8752
Daniel G MacArthurProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. d.macarthur@garvan.org.au.ORCID http://orcid.org/0000-0002-5771-2290
Broad Institute · USMassachusetts General Hospital · USUniversity of Helsinki · FIFinnish Institute for Health and Welfare · FICardiff University · GBIcahn School of Medicine at Mount Sinai · USLund University · SEUniversity of Eastern Finland · FIBrigham and Women's Hospital · USCleveland Clinic Lerner College of Medicine · USHelsinki University Hospital · FIJackson Memorial Hospital · USKarolinska Institutet · SEMcLean Hospital · USNational Heart Lung and Blood Institute · USNational University of Singapore · SGSorbonne Université · FRTampere University · FIUniversity of Tartu · EECedars-Sinai Medical Center · US
Funding
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3MGENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3MAfrican Ancestry Genomic Psychiatry CohortR01MH104964 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2015 to 2024
$16.7MGenomic Psychiatry CohortR01MH085548 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PATO, CARLOS N, PATO, MICHELE T · 2008 to 2012
$16.3MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MComputational resources for genomic interpretation of type 2 diabetesU54DK105566 · NIDDK · BROAD INSTITUTE, INC. · PI MACARTHUR, DANIEL G, NEALE, BENJAMIN MICHAEL · 2014 to 2017
$8.6MThe Child Heath Research CenterK12HD052896 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Wendy K Chung · 2007 to 2026
$7.9MLatino Ancestry Genomic Psychiatry CohortR01MH123451 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2020 to 2025
$7.1MAnnotation and interpretation of loss-of-function polymorphisms in human genomesR01GM104371 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MACARTHUR, DANIEL G · 2013 to 2016
$1.3MThe Human Knockout Project: systematic discovery of loss-of-function variants in humansF32GM115208 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KARCZEWSKI, KONRAD · 2015 to 2016
$109kBritish Heart Foundation CS/14/2/30841British Heart Foundation RG/18/10/33842Medical Research Council MC_UP_1102/20Medical Research Council MR/R006237/1NHGRI NIH HHS T32 HG002295NHGRI NIH HHS U41 HG007234NICHD NIH HHS K12 HD052896NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK043351NIDDK NIH HHS U54 DK105566NIGMS NIH HHS F32 GM115208NIGMS NIH HHS R01 GM104371NIMH NIH HHS R01 MH085548NIMH NIH HHS R01 MH104964NIMH NIH HHS R01 MH123451
Abstract
The acceleration of DNA sequencing in samples from patients and population studies has resulted in extensive catalogues of human genetic variation, but the interpretation of rare genetic variants remains problematic. A notable example of this challenge is the existence of disruptive variants in dosage-sensitive disease genes, even in apparently healthy individuals. Here, by manual curation of putative loss-of-function (pLoF) variants in haploinsufficient disease genes in the Genome Aggregation Database (gnomAD)
Indexed as
Molecular Sequence AnnotationTranscription, GeneticAutism Spectrum DisorderDatasets as TopicDevelopmental DisabilitiesDiseaseExome SequencingExonsFemaleGenotypeHaploinsufficiencyHumansIntellectual DisabilityLoss of Function MutationMalePoisson DistributionRNA, Messenger
Identifiers
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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.