Evidence map›Paper›PMID 36074821›Full record

ArticleScience (New York, N.Y.)2022

The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection.

Christopher M Richards, Sabrina Jabs, Wenjie Qiao, Lauren D Varanese, Michaela Schweizer, Peter R Mosen, Nicholas M Riley, Malte Klüssendorf, James R Zengel, Ryan A Flynn and 15 more

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
10.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
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  18. Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Lysosomes' fallback strategies: more than just survival or death.Frontiers in cell and developmental biology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 10 institutions in 3 countries.

Christopher M Richards *Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0832-8951
Sabrina Jabs *Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.ORCID 0000-0001-8065-8002
Wenjie Qiao *Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-0255-6155
Lauren D VaraneseDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-3916-8401
Michaela SchweizerDepartment of Electron Microscopy, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0001-5062-328X
Peter R MosenInstitute for Biochemistry and Molecular Biology, Medical Faculty, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany.ORCID 0000-0001-5922-3805
Nicholas M RileyDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0002-1536-2966
Malte KlüssendorfDepartment of Osteology and Biomechanics, Cell Biology of Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0001-6790-8951
James R ZengelDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-3153-3603
Ryan A FlynnStem Cell Program, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0001-5013-0442
Arjun RustagiDivision of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-6921-1012
John C WidenDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-8973-1509
Christine E PetersDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-9568-6206
Yaw Shin OoiProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.ORCID 0000-0001-9014-1365
Xuping XieDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.ORCID 0000-0003-0918-016X
Pei-Yong ShiDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.ORCID 0000-0001-5553-1616
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID 0000-0001-7450-607X
Andreas S PuschnikChan Zuckerberg Biohub, San Francisco, CA, USA.ORCID 0000-0002-9605-9458
Matthew BogyoDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-3753-4412
Carolyn R BertozziDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4482-2754
Catherine A BlishDivision of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6946-7627
Dominic WinterInstitute for Biochemistry and Molecular Biology, Medical Faculty, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany.ORCID 0000-0001-6788-6641
Claude M NagamineDepartment of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0392-4383
Thomas BraulkeDepartment of Osteology and Biomechanics, Cell Biology of Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-2336-8532
Jan E CaretteDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-5187-8070
Stanford University · USUniversität Hamburg · DEThe University of Texas Medical Branch at Galveston · USUniversity of Bonn · DEBoston Children's Hospital · USChan Zuckerberg Initiative (United States) · USChristian-Albrechts-Universität zu Kiel · DEDuke-NUS Medical School · SGGerman Cancer Research Center · DEHoward Hughes Medical Institute · US

Funding

Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
MOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9M
EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
METABOLIC OLIGOSACCHARIDE ENGINEERINGR01GM058867 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Carolyn Bertozzi · 1999 to 2026
$5.6M
Regulation of Ebola virus replication by the host ubiquitin systemR01AI134907 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GIRALDO, MARIA ISABEL · 2018 to 2022
$3.1M
Genetic screens to find critical host factors for SARS-CoV-2 infectionR01AI140186 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2019 to 2023
$2.3M
Host determinants of adeno-associated virus entry and traffickingR01AI130123 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2018 to 2022
$2.0M
Host Genes Critical for Flavivirus InfectionR01AI141970 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2019 to 2023
$2.0M
Uniting Mass Spectrometry and Glycoscience to Investigate Cancer BiologyK00CA212454 · NCI · STANFORD UNIVERSITY · PI RILEY, NICHOLAS M · 2018 to 2021
$331k
NCI NIH HHS K00 CA212454NIAID NIH HHS R01 AI130123NIAID NIH HHS R01 AI134907NIAID NIH HHS R01 AI140186NIAID NIH HHS R01 AI141970NIAID NIH HHS T32 AI007328NIAID NIH HHS T32 AI007502NIGMS NIH HHS R01 GM058867NIGMS NIH HHS T32 GM007276
6 · The paper itself

Abstract

Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging of soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens to identify lysosomal enzyme trafficking factor (LYSET, also named TMEM251) as essential for infection by cathepsin-dependent viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes.

Indexed as

COVID-19LysosomesMucolipidosesProteinsAnimalsCathepsinsHumansMannoseMembrane ProteinsMiceMice, KnockoutTransferases (Other Substituted Phosphate Groups)CathepsinsLYSET protein, humanMannoseMembrane ProteinsProteinsTransferases (Other Substituted Phosphate Groups)

Identifiers

PMID36074821
PMCPMC9547973
OpenAlexW4295082316

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Registered trials

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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.