Evidence map›Paper›PMID 41298377›Full record

ArticleNature communications2025

Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies.

Sébastien Küry, Janelle E Stanton, Geeske M van Woerden, Amélie Bosc-Rosati, Tzung-Chien Hsieh, Lise Bray, Marielle Oloudé, Cory Rosenfelt, Marie Pier Scott-Boyer, Victoria Most and 139 more

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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Review
  2. Strengthening the Role ofInternational journal of molecular sciences · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

149 authors.

Sébastien KüryNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France. sebastien.kury@chu-nantes.fr.ORCID http://orcid.org/0000-0001-5497-0465
Janelle E Stanton *Bernal Institute, University of Limerick, Limerick, Ireland.
Geeske M van Woerden *Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-2492-9239
Amélie Bosc-Rosati *Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse (UT), Toulouse, France.
Tzung-Chien Hsieh *Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-3828-4419
Lise Bray *Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Marielle Oloudé *Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.ORCID http://orcid.org/0009-0008-3600-0922
Cory Rosenfelt *Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Marie Pier Scott-BoyerCentre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
Victoria MostInstitute for Drug Discovery, Medical Faculty, Leipzig University, Leipzig, Germany.ORCID http://orcid.org/0000-0002-2263-4608
Tianyun WangDepartment of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing, China.ORCID http://orcid.org/0000-0002-5179-087X
Jonas J PapendorfUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany.
Charlotte de KoninkENCORE Center of Expertise for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands.
Wallid DebNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.ORCID http://orcid.org/0000-0002-5103-8573
Virginie VignardNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Maja Studencka-TurskiUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany.
Thomas BesnardNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.
Anna M HajdukowiczUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany.
Franziska G ThielUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany.ORCID http://orcid.org/0000-0001-6322-9222
Sophie WolfgrammUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany.ORCID http://orcid.org/0009-0004-0353-6457
Laëtitia FlorenceauNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Silvestre CuinatNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.ORCID http://orcid.org/0000-0002-0763-5661
Sylvain MarsacNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.
Yann VerrèsNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Audrey DangoumauUniversité de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, Tours, France.
Léa PoirierNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Ingrid M WentzensenGeneDx, LLC, Gaithersburg, MD, USA.
Annabelle TuttleGeneDx, LLC, Gaithersburg, MD, USA.
Cara ForsterLoyola University Chicago, Chicago, IL, USA.
Johanna StriesowLeibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.ORCID http://orcid.org/0009-0009-2931-6803
Richard GolnikDepartment of Computer Science and Interdisciplinary Center for Bioinformatics, Bioinformatics Group, Universität Leipzig, Leipzig, Germany.
Damara OrtizUPMC Children's Hospital of Pittsburgh, One Children's Hospital Drive, Pittsburgh, PA, USA.
Laura JenkinsUPMC Children's Hospital of Pittsburgh, One Children's Hospital Drive, Pittsburgh, PA, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5664-7987
Alban ZieglerDepartment of Medical Genetics, University Hospital of Toulouse, Toulouse, France.
Clara HoudayerService de Génétique médicale, CHU Angers, Angers, France.ORCID http://orcid.org/0000-0001-9010-7722
Dominique BonneauService de Génétique médicale, CHU Angers, Angers, France.
Erin TortiGeneDx, LLC, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0001-5790-1051
Amber BegtrupGeneDx, LLC, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-2872-3281
Kristin G MonaghanGeneDx, LLC, Gaithersburg, MD, USA.
Sureni V MullegamaGeneDx, LLC, Gaithersburg, MD, USA.
Catharina M L Nienke Volker-TouwDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Koen L I van GassenDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Renske OegemaDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-7146-617X
Mirjam S de PagterDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Katharina SteindlInstitute of Medical Genetics, University of Zürich, Zurich, Switzerland.
Anita RauchInstitute of Medical Genetics, University of Zürich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-2930-3163
Ivan IvanovskiInstitute of Medical Genetics, University of Zürich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-0113-783X
Kimberly McDonaldNorton Children's Medical Group, University of Louisville School of Medicine, Louisville, KY, USA.
Emily BootheUniversity of Mississippi Medical Center, Jackson, MS, USA.
Andrew DauberDivision of Endocrinology, Children's National Hospital and Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.ORCID http://orcid.org/0000-0003-4890-0262
Janice BakerDepartment of Medical Genetics and Genomics, Children's Minnesota, Minneapolis, MN, USA.
Noelle Andrea V FabieDepartment of Medical Genetics and Genomics, Children's Minnesota, Minneapolis, MN, USA.
Raphael A BernierDepartment of Psychiatry & Behavioral Sciences, Center on Human Development and Disability, University of Washington, Seattle, WA, USA.
Tychele N TurnerDepartment of Genetics, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-8246-6477
Siddharth SrivastavaRosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Kira A DiesRosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Lindsay C SwansonRosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Carrie CostinDepartment of Genetics, Akron Children's Hospital, One Perkins Square, Akron, OH, USA.
Alali AbdulrazakDivision of Genetics, Department of Pediatrics, West Virginia University School of Medicine, One Medical Center Drive, Morgantown, WV, USA.
Rebekah K JoblingDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada.
John PappasClinical Genetic Services, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-5625-2598
Rachel RabinClinical Genetic Services, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA.
Dmitriy NiyazovDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Anne Chun-Hui TsaiDepartment of Pediatrics, College of Medicine, University of Illinois, Chicago, IL, USA.
Karen KovakDepartment of Molecular and Medical Genetics, Oregon Health and Sciences University, OHSU, Portland, OR, USA.
David B BeckDivision of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-5884-6231
May Christine V MalicdanMedical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1697-6959
David R AdamsNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
Lynne WolfeNational Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7628-5741
Rebecca D GanetzkyMitochondrial Medicine Program, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Colleen C MurareskuMitochondrial Medicine Program, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Davit BabikyanDepartment of Medical Genetics, Yerevan State Medical University after Mkhitar Heratsi, Yerevan, Armenia.
Zdeněk SedláčekDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.ORCID http://orcid.org/0000-0001-6575-9163
Miroslava HančárováDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Andrew T TimberlakeWyss Department of Plastic Surgery, NYU Langone Medical Center, New York, NY, USA.
Hind Al SaifDepartment of Human and Molecular Genetics, Division of Clinical Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Berkley NestlerDepartment of Human and Molecular Genetics, Division of Clinical Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Kayla KingDepartment of Human and Molecular Genetics, Division of Clinical Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
M J HajianpourDivision of Medical Genetics and Genomics, Department of Pediatrics, Albany Medical College, Albany, NY, USA.ORCID http://orcid.org/0000-0002-2498-0870
Gregory CostainDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-0099-9945
D'Arcy PrendergastDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada.
Chumei LiMcMaster University Medical Center, Hamilton, ON, Canada.
David GenevièveUniversité Montpellier, Inserm U 1183, Centre de référence maladies rares anomalies du développement, Service de génétique médicale, Hôpital Arnaud de Villeneuve, Montpellier, France.ORCID http://orcid.org/0000-0001-6928-6287
Antonio VitobelloUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID http://orcid.org/0000-0003-3717-8374
Arthur SorlinUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID http://orcid.org/0000-0001-8008-9145
Christophe PhilippeUMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.ORCID http://orcid.org/0000-0001-7098-6520
Tamar HarelDepartment of Genetics, Hadassah Medical Organization, Jerusalem, Israel.
Ori TokerDepartment of Pediatrics, Allergy and Clinical Immunology Unit, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Ataf SabirClinical Genetics Department, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.ORCID http://orcid.org/0000-0003-4857-1964
Derek LimClinical Genetics Department, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
Mark J HamiltonWest of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK.ORCID http://orcid.org/0000-0001-9719-243X
Lisa J BrysonWest of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK.
Elaine ClearySouth East Scotland Genetics Service, Western General Hospital, Edinburgh, UK.
Sacha WeberService de Génétique Médicale, Hôpital Armand-Trousseau, APHP, Sorbonne Université, Paris, France.
Trevor L HoffmanDepartment of Genetics, Southern California Kaiser Permanente Medical Group, Anaheim, CA, USA.
Anna M Cueto-GonzálezDepartment of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.ORCID http://orcid.org/0000-0001-7694-6124
Eduardo F TizzanoDepartment of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
David Gómez-AndrésPediatric Neurology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.ORCID http://orcid.org/0000-0001-5654-7791
Marta Codina-SolàDepartment of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Athina VerveriDepartment of Genetics for Rare Diseases, 'Papageorgiou' General Hospital, Thessaloniki, Greece.
Efterpi PavlidouDepartment of Speech and Language Therapy, University Hospital of Ioannina, Ioannina, Greece.
Alexandros LambropoulosGenetic Unit, 1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, 'Papageorgiou' General Hospital, Thessaloniki, Greece.ORCID http://orcid.org/0000-0002-8887-222X
Kyriakos GarganisEpilepsy Unit, St Luke's Hospital, Thessaloniki, Greece.
Marlène RioService de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.ORCID http://orcid.org/0000-0003-2049-5058
Jonathan LevyDepartment of Genetics, APHP-Robert Debré University Hospital, Paris, France.ORCID http://orcid.org/0000-0002-8822-816X
Sarah J LangasDivision of Genetics, Genomics and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-0361-6367
Anne M McRaeDivision of Genetics, Genomics and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Mathieu K LessardDivision of Medical Genetics, Department of Specialised Medicine, McGill University Health Centre, Department of Human Genetics, McGill University, Montreal, QC, Canada.
Maria Daniela D'AgostinoDivision of Medical Genetics, Department of Specialised Medicine, McGill University Health Centre, Department of Human Genetics, McGill University, Montreal, QC, Canada.
Isabelle De BieDivision of Medical Genetics, Department of Specialised Medicine, McGill University Health Centre, Department of Human Genetics, McGill University, Montreal, QC, Canada.
Meret WeglerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Rami Abou JamraInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.ORCID http://orcid.org/0000-0002-1542-1399
Susanne B KamphausenInstitute of Human Genetics, University Hospital Magdeburg, University Hospital Magdeburg, Magdeburg, Germany.
Viktoria BotheInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Lorraine PotockiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Eric OlingerCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Yves SznajerCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Elsa WiameCenter for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Michelle L ThompsonDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA.
Molly C SchroederDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA.
Catherine GoochDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Washington University in St Louis, St. Louis, MO, USA.
Raphael A SmithDepartment of Pediatrics, Division of Genetics and Metabolism, University of North Carolina Health, Chapel Hill, NC, USA.
Arti PandyaDepartment of Pediatrics, Division of Genetics and Metabolism, University of North Carolina Health, Chapel Hill, NC, USA.
Larissa M BuschUniversitätsmedizin Greifswald, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung für Funktionelle Genomforschung, Greifswald, Germany.ORCID http://orcid.org/0000-0002-9545-6355
Uwe VölkerUniversitätsmedizin Greifswald, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung für Funktionelle Genomforschung, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5689-3448
Elke HammerUniversitätsmedizin Greifswald, Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung für Funktionelle Genomforschung, Greifswald, Germany.ORCID http://orcid.org/0000-0002-1507-0402
Kristian WendeLeibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.ORCID http://orcid.org/0000-0001-5217-0683
Benjamin CognéNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.ORCID http://orcid.org/0000-0002-5503-6292
Bertrand IsidorNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.
Jens MeilerInstitute for Drug Discovery, Medical Faculty, Leipzig University, Leipzig, Germany.ORCID http://orcid.org/0000-0001-8945-193X
Clémentine RipollICV-iPS core facility, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
Stéphanie BigouICV-iPS core facility, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.ORCID http://orcid.org/0000-0002-6328-0703
Frédéric LaumonnierUniversité de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, Tours, France.ORCID http://orcid.org/0000-0003-2567-0708
Peter W HildebrandInstitut für Medizinische Physik und Biophysik, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany.ORCID http://orcid.org/0000-0003-0063-1104
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8246-4014
Kirsty McWalterGeneDx, LLC, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-1654-9036
Peter M KrawitzInstitute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0008-1789-3200
Florence Roux-DalvaiCentre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.ORCID http://orcid.org/0000-0002-9961-8964
Ype ElgersmaDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-3758-1297
Julien MarcouxInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse (UT), Toulouse, France.ORCID http://orcid.org/0000-0001-7321-7436
Marie-Pierre BousquetInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse (UT), Toulouse, France.ORCID http://orcid.org/0000-0003-2680-8932
Arnaud DroitCentre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.ORCID http://orcid.org/0000-0001-7922-790X
Jeremie PoschmannNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.ORCID http://orcid.org/0000-0002-9613-5297
Andreas M GrabruckerBernal Institute, University of Limerick, Limerick, Ireland.ORCID http://orcid.org/0000-0003-0005-4810
Francois V BolducDepartment of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Stéphane BézieauNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France. stephane.bezieau@chu-nantes.fr.ORCID http://orcid.org/0000-0003-0095-1319
Frédéric EbsteinNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France. frederic.ebstein@univ-nantes.fr.ORCID http://orcid.org/0000-0002-3729-7878
Elke KrügerUniversitätsmedizin Greifswald, Institut für Medizinische Biochemie und Molekularbiologie, Greifswald, Germany. elke.krueger@uni-greifswald.de.ORCID http://orcid.org/0000-0002-2551-242X

Funding

Sporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2M
Noncoding mutations in neurodevelopmental disordersR01MH126933 · NIMH · WASHINGTON UNIVERSITY · PI Tychele Naomi Turner · 2022 to 2026
$3.6M
Investigating the Genetic Landscape of Cerebral PalsyK23NS119666 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI SRIVASTAVA, SIDDHARTH · 2021 to 2025
$1.1M
Agence Nationale de la Recherche (French National Research Agency) ANR-10- IAIHU-06Agence Nationale de la Recherche (French National Research Agency) ANR-21-CE17-0005Agence Nationale de la Recherche (French National Research Agency) ANR-22-RAR4-0001-01AXA Research Fund (Le Fonds AXA pour la Recherche) TND-UPSCentre Hospitalier Universitaire de Nantes (CHU de Nantes) PROG/09/72-03Centre Hospitalier Universitaire de Nantes (CHU de Nantes) RC22_0020Deutsche Forschungsgemeinschaft (German Research Foundation) RTG PRO 2719Deutsche Forschungsgemeinschaft (German Research Foundation) SPP 2453 KR1915/11-1European Cooperation in Science and Technology (COST) ProteoCure CA20113National Natural Science Foundation of China (National Science Foundation of China) 82201314NIMH NIH HHS R01 MH101221NIMH NIH HHS R01 MH126933NINDS NIH HHS K23 NS119666U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) R01MH101221U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) K23NS119666
6 · The paper itself

Abstract

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor cell stemness, causing deficits in higher-order functions, including learning and locomotion. Pharmacological targeting of integrated stress response kinases reveals a mechanistic link between proteotoxic stress and spontaneous type I interferon activation. These findings expand our understanding of proteasome-dependent quality control in neurodevelopment and suggest potential therapeutic strategies for neurodevelopmental proteasomopathies.

Indexed as

Adenosine TriphosphatasesNeurodevelopmental DisordersNeuronsProteasome Endopeptidase ComplexAnimalsATPases Associated with Diverse Cellular ActivitiesChildDrosophila melanogasterDrosophila ProteinsFemaleHumansMaleMitochondriaAdenosine TriphosphatasesATPases Associated with Diverse Cellular ActivitiesDrosophila ProteinsProteasome Endopeptidase Complex

Identifiers

PMID41298377
PMCPMC12658096

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