ArticleNature communications2021
Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
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.
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.
Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Diagnostic utility of clinical genome reanalysis in rare pediatric disorders using long-read sequencing.HGG advances · 2026Article
- Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.Translational psychiatry · 2026Article
- Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology.European journal of human genetics : EJHG · 2026Article
- De novo variants in KDM2A cause a syndromic neurodevelopmental disorder.American journal of human genetics · 2026Article
- Bi-allelic variants in the ribosomal protein RPS6KC1 cause a complex neurodevelopmental disorder.American journal of human genetics · 2025Article
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- Unlocking biological insights from differentially expressed genes: Concepts, methods, and future perspectives.Journal of advanced research · 2025Review
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy.International journal of molecular sciences · 2024Article
- Oligomerization regulates the interaction of Gemin5 with members of the SMN complex and the translation machinery.Cell death discovery · 2024Article
- Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies.Brain and behavior · 2024Article
- Mutations of GEMIN5 are associated with coenzyme QEuropean journal of human genetics : EJHG · 2024Article
- The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.Biochemical Society transactions · 2024Review
- Alternative splicing events driven by altered levels of GEMIN5 undergo translation.RNA biology · 2024Article
- Drosha-dependent microRNAs modulate FUS-mediated neurodegeneration in vivo.Nucleic acids research · 2023Article
- Characterizing proteomic and transcriptomic features of missense variants in amyotrophic lateral sclerosis genes.Brain : a journal of neurology · 2023Article
- Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gene in two Chinese families.Journal of human genetics · 2023Article
- Article
- SMN regulates GEMIN5 expression and acts as a modifier of GEMIN5-mediated neurodegeneration.Acta neuropathologica · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
70 authors at 20 institutions in 11 countries.
Sukhleen Kour *Department of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-8068-5278
Deepa S Rajan *Department of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Tyler R FortunaDepartment of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Eric N AndersonDepartment of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Caroline WardDepartment of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Youngha LeeDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sangmoon LeeDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yong Beom ShinDepartment of Rehabilitative Medicine, Pusan National University School of Medicine, Pusan, Republic of Korea.
Jong-Hee ChaeDepartment of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Murim ChoiDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-9195-1455
Karine SiquierDevelopmental Brain Disorders Laboratory, Paris University, Imagine Institute, INSERM UMR, Paris, France.
Vincent CantagrelDevelopmental Brain Disorders Laboratory, Paris University, Imagine Institute, INSERM UMR, Paris, France.ORCID 0000-0002-5180-4848
Jeanne AmielDepartment of Genetics, AP-HP, Necker Enfants Malades Hospital, Paris University, Imagine Institute, Paris, France.
Elliot S StolermanGreenwood Genetic Center, Greenwood, SC, USA.
Sarah S BarnettDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Margot A CousinCenter for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-6119-9346
Diana CastroDepartment of Pediatrics and Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kimberly McDonaldUniversity of Mississippi Medical Center, Jackson, MS, USA.
Brian KirmseDivision of Genetics, University of Mississippi Medical Center, Jackson, MS, USA.
Andrea H NemethNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Dhivyaa RajasundaramDepartment of Pediatrics, Division of Health Informatics, Childrens Hospital of Pittsburgh, Pittsburgh, PA, USA.
A Micheil InnesDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.ORCID 0000-0001-9881-5467
Danielle LynchDepartment of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Patrick FroskDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.ORCID 0000-0002-9673-795X
Abigail CollinsDepartment of Pediatrics and Neurology, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
Melissa GibbonsDepartment of Pediatrics and Neurology, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
Michele YangDepartment of Pediatrics and Neurology, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
Isabelle DesguerreDepartment of Pediatric Neurology, AP-HP, Necker Enfants Malades Hospital, Paris University Imagine Institute, Paris, France.
Nathalie BoddaertDepartment of Pediatric Radiology, AP-HP, Necker Enfants Malades Hospital, Paris University Imagine Institute, Paris, France.
Cyril GitiauxDepartment of Pediatric Neurophysiology AP-HP, Necker Enfants Malades Hospital, Paris University, Paris, France.
Siri Lynne RydningDepartment of Neurology, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-9584-0325
Kaja K SelmerDepartment of Research and Development, Division of Neuroscience, Oslo University Hospital and the University of Oslo, Oslo, Norway.
Roser UrreiztiDepartment of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu and CIBERER, Barcelona, Spain.ORCID 0000-0003-3617-7134
Alberto Garcia-OguizaHospital Universitario Miguel Servet, Zaragoza, Spain.
Andrés Nascimento OsorioHospital Sant Joan de Déu, Barcelona, Spain.
Edgard VerduraCentre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
Aurora PujolCentre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.ORCID 0000-0002-9606-0600
Hannah R McCurryCenter for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Sameer AgnihotriDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
E Corina AndriescuDepartment of Pediatrics, University of Texas Health Science Center, Houston, TX, USA.
Shade B MoodyDepartment of Pediatrics, University of Texas Health Science Center, Houston, TX, USA.
Chanika PhornphutkulDepartment of Pediatrics, Division of Human Genetics, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA.
Maria J Guillen SacotoGeneDx, Gaithersburg, MD, USA.
Amber BegtrupGeneDx, Gaithersburg, MD, USA.ORCID 0000-0002-2872-3281
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-2866-7777
Janbernd KirschnerDepartment of Neuropediatrics and Muscle Disorders, Medical Center,, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
David SchorlingDepartment of Neuropediatrics and Muscle Disorders, Medical Center,, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sabine Rudnik-SchönebornDivision of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
Tim M StromInstitute of Human Genetics, Faculty of Medicine, Technical University Munich, Munich, Germany.
Steffen LeizClinic for Children and Adolescents Dritter Orden, Divison of Neuropediatrics, Munchen, Germany.
Kali JulietteDepartment of Neurology, Gillette Children's Specialty Healthcare, St Paul, MN, USA.
Randal RichardsonDepartment of Neurology, Gillette Children's Specialty Healthcare, St Paul, MN, USA.
Ying YangDepartment of Pediatrics, Peking University First Hospital, Beijing, China.
Yuehua ZhangDepartment of Pediatrics, Peking University First Hospital, Beijing, China.
Minghui WangThe First People's Hospital of Changde City, Hunan, China.
Jia WangCipher Gene Ltd, Beijing, China.
Xiaodong WangCipher Gene Ltd, Beijing, China.ORCID 0000-0002-5374-0235
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Matias WagnerInstitute of Human Genetics, Klinikum rechts der IsarTechnical, University of Munich, Munich, Germany.ORCID 0000-0002-4454-8823
Mahmoud Y IssaClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.ORCID 0000-0002-3899-2821
Hasnaa M ElbendaryClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Valentina StanleyDepartments of Neurosciences and Pediatrics, Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Reza MaroofianDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Joseph G GleesonDepartments of Neurosciences and Pediatrics, Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-0889-9220
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.ORCID 0000-0001-7840-0002
Jan SenderekDepartment of Neurology, Friedrich-Baur-Institute, University Hospital, LMU Munich, Munich, Germany.
Udai Bhan PandeyDepartment of Pediatrics, Childrens Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. udai@pitt.edu.ORCID 0000-0002-6267-0179
Children's Hospital of Pittsburgh · USSeoul National University · KRAssistance Publique – Hôpitaux de Paris · FRChildren's Hospital Colorado · USNational Research Centre · EGChildren’s Institute · USCipher Gene (China) · CNGillette Children's Specialty Healthcare · USInserm · FRJackson Memorial Hospital · USNational Hospital for Neurology and Neurosurgery · GBNational Institutes of Health · USOslo University Hospital · NOPeking University · CNThe University of Texas Health Science Center at Houston · USUniversity of Calgary · CAUniversity of Freiburg · DEUniversity of Pittsburgh · USBroad Institute · USBrown University · US
Funding
Molecular and Clinical Manifestations of Matrix and Aggregate MyopathiesZIANS003129 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BÖNNEMANN, CARSTEN · 2011 to 2025
$52.8MJoint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MWaisman Intellectual and Developmental Disabilities Research Center Down Syndrome RegistryU54HD090256 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI POLLAK, SETH D · 2016 to 2020
$6.0MTraining in the Neurobiology of Neurological DiseaseT32NS086749 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Omar El Gharbawie, REBECCA P SEAL · 2014 to 2026
$4.8MIdentification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6MMolecular Characterization of Pontocerebellar HypoplasiaR01NS098004 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOSEPH G GLEESON · 2016 to 2026
$4.6MIdentification and Characterization of ALS/FTD Associated Variants Using Whole Genome SequencingR56NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2020 to 2020
$586kHoward Hughes Medical InstituteNHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1 HG008900NICHD NIH HHS U54 HD090256NINDS NIH HHS R01 NS073873NINDS NIH HHS R01 NS098004NINDS NIH HHS R56 NS073873NINDS NIH HHS T32 NS086749
Abstract
GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism. GEMIN5 mutations result in disruption of snRNP complex assembly formation in patient iPSC neurons. Furthermore, knock down of rigor mortis, the fly homolog of human GEMIN5, leads to developmental defects, motor dysfunction, and a reduced lifespan. Interestingly, we observed that GEMIN5 variants disrupt a distinct set of transcripts and pathways as compared to SMA patient neurons, suggesting different molecular pathomechanisms. These findings collectively provide evidence that pathogenic variants in GEMIN5 perturb physiological functions and result in a neurodevelopmental delay and ataxia syndrome.
Indexed as
AllelesAmino Acid SequenceAnimalsChild, PreschoolDevelopmental DisabilitiesDrosophilaFemaleGene Expression Regulation, DevelopmentalGene Knockdown TechniquesGene OntologyHEK293 CellsHumansInduced Pluripotent Stem CellsLoss of Function MutationMaleMuscle HypotoniaGEMIN5 protein, humanRibonucleoproteins, Small NuclearSMN Complex Proteins
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.