ArticleNeuron2014
Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01459302 (Family Studies in Neuromuscular Disorders), which is not on this map. Cited by 206 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed, 2 pooled it
23.7field-weighted citation impact, top 1% 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.
Family Studies in Neuromuscular Disorders
Who cites it
206 citing papers in PubMed, 2 syntheses or guidelines pooled it, 368 citations in OpenAlex.
- Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.Disease models & mechanisms · 2022Pooled it
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Missense variants in TUBA4A cause myo-tubulinopathies.Brain : a journal of neurology · 2026Article
- Familial, neuropathological and cellular analysis identify ARPP21 as a major amyotrophic lateral sclerosis associated gene in French cohorts.Acta neuropathologica · 2026Article
- TUBA4A Pathogenic Variant Manifesting With Adulthood-Onset Genetic Myasthenic Syndrome, Myopathy, and Infertility.European journal of neurology · 2026Article
- A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.Human molecular genetics · 2026Article
- A transcriptional atlas of gyrification reveals dynamic spatio-temporal gene expression in the developing ferret cortex.Brain structure & function · 2026Article
- TUBA4A: The Tale of an Unconventional Tubulin.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Bridging the gap: an emerging link between tubulinopathies and ciliopathies.NPJ genomic medicine · 2026Review
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation inbioRxiv : the preprint server for biology · 2026Article
- Mutant TDP-43 drives impairments in axonal transport and glycolysis in a mouse stem-cell-derived motor neuron model of amyotrophic lateral sclerosis (ALS).Cell death & disease · 2026Article
- Review
- Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?Neurobiology of disease · 2026Review
- Mutations in the β-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes.Nature communications · 2025Article
- Concurrent nanotherapeutics and regulatory updates for the management of amyotrophic lateral sclerosis: a focused review for orphan drug (Tofersen).Orphanet journal of rare diseases · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- SpliPath enhances disease gene discovery in case-control analyses of rare splice-altering genetic variants.Cell reports methods · 2025Article
- Novel Cross-Cancer Hub Genes in Doxorubicin Resistance Identified by Transcriptional Mapping.Biomedicines · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
146 more citing papers are in PubMed but not listed here.
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Authors and funding
66 authors at 20 institutions in 8 countries.
Bradley N SmithCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Nicola TicozziDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy; Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy.
Claudia FalliniDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Athina Soragia GkaziCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Simon ToppCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Kevin P KennaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Republic of Ireland.
Emma L ScotterCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Jason KostDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Bioinformatics and Computational Biology, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Pamela KeagleDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jack W MillerCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Daniela CaliniDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy; Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy.
Caroline VanceCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Eric W DanielsonDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Claire TroakesCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Cinzia TilocaDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy.
Safa Al-SarrajCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Elizabeth A LewisDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Andrew KingCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
Claudia ColombritaDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy; Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy.
Viviana PensatoUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy.
Barbara CastellottiUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy.
Jacqueline de BellerocheNeurogenetics Group, Division of Brain Sciences, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
Frank BaasDepartment of Genome analysis and Neurogenetics, Academic Medical Centre, Amsterdam, The Netherlands.
Anneloor L M A ten AsbroekDepartment of Genome analysis and Neurogenetics, Academic Medical Centre, Amsterdam, The Netherlands.
Peter C SappDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Diane McKenna-YasekDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Russell L McLaughlinAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Republic of Ireland.
Meraida PolakDepartment of Neurology, Emory University, Atlanta, GA 30322, USA.
Seneshaw AsressDepartment of Neurology, Emory University, Atlanta, GA 30322, USA.
Jesús Esteban-PérezUnidad de ELA, Instituto de Investigación Hospital 12 de Octubre de Madrid, SERMAS, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U-723), 28041 Madrid, Spain.
José Luis Muñoz-BlancoUnidad de ELA, Instituto de Investigación Hospital Gregorio Marañón de Madrid, SERMAS, 28007 Madrid, Spain.
Michael SimpsonDepartment of Genetics and Molecular Medicine, King's College London, Tower Wing, Guy's Hospital, London, SE1 7EH, UK.
SLAGEN Consortium
Wouter van RheenenDepartment of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, 3508 GA Utrecht, the Netherlands.
Frank P DiekstraDepartment of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, 3508 GA Utrecht, the Netherlands.
Giuseppe Lauria3rd Neurology Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy.
Stefano DugaDepartment of Medical Biotechnology and Translational Medicine - Università degli Studi di Milano, 20133 Milan, Italy.
Stefania CortiDepartment of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy; Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Cristina CeredaExperimental Neurobiology Laboratory, IRCCS 'C. Mondino' National Neurological Institute, 27100 Pavia, Italy.
Lucia CorradoDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), "A. Avogadro" University, 28100 Novara, Italy.
Gianni SorarùDepartment of Neurosciences, University of Padova, 35122 Padova, Italy.
Karen E MorrisonSchool of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK; Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2WB, UK.
Kelly L WilliamsAustralian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.
Garth A NicholsonAustralian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia; Northcott Neuroscience Laboratory, University of Sydney, ANZAC Research Institute, Sydney, NSW 2139, Australia.
Ian P BlairAustralian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.
Patrick A DionMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3801 Montreal, QC H3A 2B4, Canada.
Claire S LeblondMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3801 Montreal, QC H3A 2B4, Canada.
Guy A RouleauMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3801 Montreal, QC H3A 2B4, Canada.
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Republic of Ireland.
Jan H VeldinkDepartment of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, 3508 GA Utrecht, the Netherlands.
Leonard H van den BergDepartment of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, 3508 GA Utrecht, the Netherlands.
Ammar Al-ChalabiDepartment of Clinical Neuroscience, Medical Research Council Centre for Neurodegeneration Research, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, WC2R 2LS, UK.
Hardev PallSchool of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Pamela J ShawSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, S10 2HQ, UK.
Martin R TurnerNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Kevin TalbotNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Franco TaroniUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy.
Alberto García-RedondoUnidad de ELA, Instituto de Investigación Hospital 12 de Octubre de Madrid, SERMAS, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U-723), 28041 Madrid, Spain.
Zheyang WuDepartment of Bioinformatics and Computational Biology, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Jonathan D GlassDepartment of Neurology, Emory University, Atlanta, GA 30322, USA.
Cinzia GelleraUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy.
Antonia RattiDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy; Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy.
Robert H BrownDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Vincenzo SilaniDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy; Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center - Università degli Studi di Milano, 20122 Milan, Italy.
Christopher E ShawCentre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, London, SE5 8AF, UK.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: john.landers@umassmed.edu.
King's College London · GBUniversity of Massachusetts Chan Medical School · USUniversity of Milan · ITFondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity Medical Center Utrecht · NLEmory University · USMontreal Neurological Institute and Hospital · CAAmsterdam UMC Location University of Amsterdam · NLMacquarie University · AUResearch Institute Hospital 12 de Octubre · ESTrinity College Dublin · IEUniversity of Oxford · GBWorcester Polytechnic Institute · USGuy's Hospital · GBHammersmith Hospital · GBHospital General Universitario Gregorio Marañón · ESIRCCS Istituto Auxologico Italiano · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITThe University of Sydney · AUUniversity Hospitals Birmingham NHS Foundation Trust · GB
Funding
The Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2005 to 2019
$25.7MIdentification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6MCharacterization of KIFAP3, a Modifier of Survival in Sporadic ALSR01NS065847 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2010 to 2014
$1.8MMedical Research Council G0600974Medical Research Council G1100695Medical Research Council MR/K01014X/1Medical Research Council MR/L016397/1Medical Research Council MR/L501529/1Motor Neurone Disease Association TURNER/JAN13/944-795NIA NIH HHS P50 AG025688NINDS NIH HHS R01 NS065847NINDS NIH HHS R01 NS073873Wellcome Trust 089701
Abstract
Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis.
Indexed as
Genetic Predisposition to DiseaseAmyotrophic Lateral SclerosisBrainExomeHumansMutationNeuronsSequence Analysis, DNATubulinTUBA1A protein, humanTubulin
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NCT01459302ClinicalTrials.gov
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.