ArticleNature communications2020
Human and mouse essentiality screens as a resource for disease gene discovery.
Open access · goldAbstract readEvaluation Study
In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits.Genome medicine · 2022Pooled it
- Article
- Overcoming the challenges of genome-editing essential genes.STAR protocols · 2026Review
- Engineered bipaternal mice reveal the consequences of life without a maternal genomic contribution.PLoS biology · 2026Article
- Flux sampling and graph neural networks for improved gene essentiality prediction in mammalian genome-scale metabolic models.NPJ systems biology and applications · 2026Article
- The Human Pleiotropic Map of GWAS Associations and Therapeutic Implications.bioRxiv : the preprint server for biology · 2026Article
- The redundant protein synthesis gene Aimp1 challenges the canonical inverse relationship between translation and autophagy.Communications biology · 2026Article
- Degron models: a toolbox for rapid in vivo depletion of essential proteins regulating mRNA metabolism.Communications biology · 2026Article
- Loss of CTLH component MAEA impairs DNA repair and replication and leads to developmental delay.EMBO molecular medicine · 2026Article
- International Mouse Phenotyping Consortium Portal: facilitating investigation of gene function and providing insights into human disease.Nucleic acids research · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Site-specific DNA insertion into the human genome with engineered recombinases.Nature biotechnology · 2025Article
- International Mouse Phenotyping Consortium: Investigating gene function and providing insights into human disease.bioRxiv : the preprint server for biology · 2025Article
- Functional Determinants and Evolutionary Consequences of Pleiotropy in Complex and Mendelian Traits.Molecular biology and evolution · 2025Article
- Accurate prediction of gene deletion phenotypes with Flux Cone Learning.Nature communications · 2025Article
- Assessing tissue-specific gene expression of essential genes from human and mouse.Briefings in bioinformatics · 2025Article
- A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects.PLoS genetics · 2025Article
- Natural dispersal is better than translocation for reducing risks of inbreeding depression in eastern black rhinoceros (Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- IMPC impact on preclinical mouse models.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Unique signatures of highly constrained genes across publicly available genomic databases.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 15 institutions in 7 countries.
Pilar Cacheiro *Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-6335-8208
Violeta Muñoz-Fuentes *European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.ORCID http://orcid.org/0000-0003-3574-546X
Stephen A MurrayThe Jackson Laboratory, Bar Harbor, ME, 4609, USA.
Mary E DickinsonDepartments of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
Maja BucanDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Lauryl M J NutterThe Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.ORCID http://orcid.org/0000-0001-9619-146X
Kevin A PetersonThe Jackson Laboratory, Bar Harbor, ME, 4609, USA.ORCID http://orcid.org/0000-0001-8353-3694
Hamed HaselimashhadiEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.ORCID http://orcid.org/0000-0001-7334-2421
Ann M FlennikenThe Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5T 3H7, Canada.
Hugh MorganMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Henrik WesterbergMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Tomasz KonopkaClinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0003-3042-4712
Chih-Wei HsuDepartments of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0002-9591-9567
Audrey ChristiansenDepartments of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
Denise G LanzaDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0001-8750-6933
Arthur L BeaudetDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
Jason D HeaneyDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0001-8475-8828
Helmut FuchsGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-5143-2677
Valerie Gailus-DurnerGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-6076-0111
Tania SorgUniversité de Strasbourg, CNRS, INSERM, Institut Clinique de la Souris, PHENOMIN-ICS, 67404, Illkirch, France.
Jan ProchazkaCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, 252 50, Prague, Czech Republic.
Vendula NovosadovaCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, 252 50, Prague, Czech Republic.
Christopher J LelliottWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0001-8087-4530
Hannah Wardle-JonesWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Sara WellsMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Lydia TeboulMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Heather CaterMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Michelle StewartMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Tertius HoughMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Wolfgang WurstInstitute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764, Neuherberg, Germany.
Radislav SedlacekCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, 252 50, Prague, Czech Republic.
David J AdamsWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0001-9490-0306
John R SeavittDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
Glauco Tocchini-ValentiniMonterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00015, Monterotondo Scalo, Italy.
Fabio MammanoMonterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00015, Monterotondo Scalo, Italy.ORCID http://orcid.org/0000-0003-3751-1691
Robert E BraunThe Jackson Laboratory, Bar Harbor, ME, 4609, USA.
Colin McKerlieThe Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.ORCID http://orcid.org/0000-0002-2232-0967
Yann HeraultUniversité de Strasbourg, CNRS, INSERM, Institut de Génétique, Biologie Moléculaire et Cellulaire, Institut Clinique de la Souris, IGBMC, PHENOMIN-ICS, 67404, Illkirch, France.ORCID http://orcid.org/0000-0001-7049-6900
Martin Hrabě de AngelisGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-7898-2353
Ann-Marie MallonMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
K C Kent LloydMouse Biology Program, University of California, Davis, CA, 95618, USA.ORCID http://orcid.org/0000-0002-5318-4144
Steve D M BrownMedical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
Helen ParkinsonEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Terrence F Meehan *European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Damian Smedley *Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. d.smedley@qmul.ac.uk.ORCID http://orcid.org/0000-0002-5836-9850
Genomics England Research Consortium
International Mouse Phenotyping Consortium
Genomics England · GBJackson Laboratory · USWellcome Sanger Institute · GBQueen Mary University of London · GBHelmholtz Zentrum München · DEMary Lyon Centre at MRC Harwell · GBCentre National de la Recherche Scientifique · FRBaylor College of Medicine · USEuropean Bioinformatics Institute · GBCzech Academy of Sciences, Institute of Molecular Genetics · CZHospital for Sick Children · CANational Research Council · ITMount Sinai Hospital · CAUniversity of California, Davis · USUniversity of Pennsylvania · US
Funding
UM1HG006348: Cas9 Genome Integrity Supplemental ProposalUM1HG006348 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI Jason D. Heaney, Chih-Wei Logan Hsu · 2016 to 2026
$47.5MKOMP2-Phase3 Production and Phenotyping by the DTCC Consortium TCP Transfer to UC DavisUM1OD023221 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KC KENT LLOYD · 2016 to 2026
$45.7MMouse Phenotyping Informatics Infrastructure - MP12UM1HG006370 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Pilar Cacheiro Martinez, Helen Elizabeth Parkinson · 2016 to 2026
$20.4MKOMP Phase II Mouse Production and CryopreservationU42OD011175 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2012 to 2015
$18.9MCRSPR II Supplement: Consortium for the production and cryopreservation of knockout miceU42OD011174 · OD · BAYLOR COLLEGE OF MEDICINE · PI BEAUDET, ARTHUR L. · 2012 to 2015
$17.7MJoint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MKOMP Phase II Mouse PhenotypingU54HG006364 · NHGRI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2011 to 2015
$16.3MUW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MMouse Phenotyping Informatics Infrastruture - MP12U54HG006370 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI BROWN, STEVE, FLICEK, PAUL · 2011 to 2015
$11.4MMedical Research Council MC_U142684171Medical Research Council MC_U142684172Medical Research Council MC_UP_1502/1Medical Research Council MR/S006753/1NHGRI NIH HHS U54 HG006364NHGRI NIH HHS U54 HG006370NHGRI NIH HHS UM1 HG006348NHGRI NIH HHS UM1 HG006493NHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1 HG006542NHGRI NIH HHS UM1 HG008900NIH HHS U42 OD011174NIH HHS U42 OD011175NIH HHS UM1 OD023221Wellcome Trust
Abstract
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.
Indexed as
AnimalsDiseaseGenes, EssentialGenetic Association StudiesGenomicsHumansMiceMice, Knockout
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