Evidence map›Paper›PMID 27231142›Full record

ArticleNature communications2016

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Karin Tuschl, Esther Meyer, Leonardo E Valdivia, Ningning Zhao, Chris Dadswell, Alaa Abdul-Sada, Christina Y Hung, Michael A Simpson, W K Chong, Thomas S Jacques and 30 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 3 pooled it
23.9field-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

186 citing papers in PubMed, 3 syntheses or guidelines pooled it, 314 citations in OpenAlex.

  1. Pooled it
  2. Genotype-Phenotype Relations for the Dystonia-Parkinsonism GenesInternational journal of molecular sciences · 2025
    Pooled it
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  20. Removal of Toxic Metabolites-Chelation: Manganese Disorders.Journal of inherited metabolic disease · 2025
    Review

126 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 18 institutions in 10 countries.

Karin TuschlGenetics and Genomic Medicine, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Esther MeyerDevelopmental Neurosciences, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Leonardo E ValdiviaDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Ningning ZhaoDepartment of Cell, Development and Cancer Biology, Oregon Health &Sciences University, Portland, Oregon 97239, USA.
Chris DadswellDepartment of Chemistry, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
Alaa Abdul-SadaDepartment of Chemistry, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
Christina Y HungDivision of Genetics and Genomics, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Michael A SimpsonDivision of Genetics and Molecular Medicine, King's College London School of Medicine, London SE1 9RT, UK.
W K ChongDepartment of Radiology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK.
Thomas S JacquesDevelopmental Biology and Cancer, UCL Institute of Child Health and Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK.
Randy L WoltjerDepartment of Pathology, Oregon Health &Science University, Portland, Oregon 97239, USA.
Simon EatonDevelopmental Biology and Cancer Programme, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Allison GregoryDepartment of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon 97239, USA.
Lynn SanfordDepartment of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon 97239, USA.
Eleanna KaraInstitute of Neurology, University College London, London WC1N 3BG, UK.
Henry HouldenInstitute of Neurology, University College London, London WC1N 3BG, UK.
Stephan M CunoInstitute of Human Genetics, Technische Universität München, Munich 81675, Germany.
Holger ProkischInstitute of Human Genetics, Technische Universität München, Munich 81675, Germany.ORCID 0000-0003-2379-6286
Lorella VallettaUnit of Molecular Neurogenetics, IRCCS, Foundation Neurological Institute 'C. Besta', Milan 20133, Italy.
Valeria TirantiUnit of Molecular Neurogenetics, IRCCS, Foundation Neurological Institute 'C. Besta', Milan 20133, Italy.ORCID 0000-0002-3584-7338
Rasha YounisDepartment of Medical and Molecular Genetics, University of Birmingham, Birmingham B15 2TT, UK.
Eamonn R MaherCentre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
John SpencerDepartment of Chemistry, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
Ania Straatman-IwanowskaMRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK.
Paul GissenGenetics and Genomic Medicine, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-9712-6122
Laila A M SelimDepartment of Paediatric Neurology, Faculty of Medicine, Cairo University Children's Hospital, Cairo 11432, Egypt.
Guillem Pintos-MorellDepartment of Paediatrics, Section of Paediatric Nephrology, Genetics and Metabolism, Unit of Rare Diseases, University Hospital 'Germans Trias I Pujol', Universitat Autònoma de Barcelona, Badalona 08916, Spain.ORCID 0000-0002-9347-2386
Wifredo Coroleu-LletgetDepartment of Paediatrics, Paediatric Neurology and Neonatology Unit, University Hospital 'Germans Trias I Pujol', Badalona 08916, Spain.
Shekeeb S MohammadNeuroimmunology Group, Institute for Neuroscience and Muscle Research, Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead NSW 2145, Australia.ORCID 0000-0003-1219-4781
Sangeetha YoganathanDepartment of Neurological Sciences, Christian Medical College Hospital, Vellore 632 004, India.
Russell C DaleNeuroimmunology Group, Institute for Neuroscience and Muscle Research, Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead NSW 2145, Australia.
Maya ThomasDepartment of Neurological Sciences, Christian Medical College Hospital, Vellore 632 004, India.
Jason RihelDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.ORCID 0000-0003-4067-2066
Olaf A BodamerDivision of Genetics and Genomics, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Caroline A EnnsDepartment of Cell, Development and Cancer Biology, Oregon Health &Sciences University, Portland, Oregon 97239, USA.
Susan J HayflickDepartment of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon 97239, USA.
Peter T ClaytonGenetics and Genomic Medicine, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Philippa B MillsGenetics and Genomic Medicine, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Manju A KurianDevelopmental Neurosciences, UCL Institute of Child Health, University College London, London WC1N 1EH, UK.
Stephen W WilsonDepartment of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.ORCID 0000-0002-8557-5940
Institute of Child Health · INOregon Health & Science University · USUniversity College London · GBGreat Ormond Street Hospital · GBUniversity of Sussex · GBBoston Children's Hospital · USChildren's Hospital at Westmead · AUChristian Medical College, Vellore · INFondazione IRCCS Istituto Neurologico Carlo Besta · ITHelmholtz Zentrum München · DECairo University · EGHospital Universitari Germans Trias i Pujol · ESKing's College London · GBMassachusetts General Hospital · USMRC Laboratory for Molecular Cell Biology · GBUniversitat Autònoma de Barcelona · ESUniversity of Birmingham · GBUniversity of Cambridge · GB

Funding

Function of the hemochromatosis proteinR37DK054488 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI ENNS, CAROLINE · 2010 to 2019
$4.0M
Regulation and function of transferrin receptor 2R01DK072166 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI ENNS, CAROLINE · 2005 to 2017
$3.7M
Mechanisms of iron-dependent regulation of ZIP-14K99DK104066 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI ZHAO, NINGNING · 2014 to 2015
$180k
Medical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MR/J004758/1Medical Research Council MR/L003775/1NIDDK NIH HHS K99 DK104066NIDDK NIH HHS R01 DK072166NIDDK NIH HHS R37 DK054488Wellcome Trust
6 · The paper itself

Abstract

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.

Indexed as

HomeostasisMutationAdolescentAnimalsCation Transport ProteinsChildChild, PreschoolDystonic DisordersFemaleGenetic Predisposition to DiseaseHEK293 CellsHumansMaleManganeseParkinsonian DisordersPedigreeCation Transport ProteinsManganeseSLC39A14 protein, human

Identifiers

PMID27231142
PMCPMC4894980
OpenAlexW2401922463

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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.