ArticleAmerican journal of human genetics2023
Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 21 papers.
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0cells of the map it votes in
21citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
What it found
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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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders.American journal of human genetics · 2026Article
- GA4GH phenopacket-driven characterization of genotype-phenotype correlations in Mendelian disorders.American journal of human genetics · 2026Article
- Outcome strategies for clinical trials in Neuropaediatric rare diseases.Neuroscience applied · 2026Review
- MLE/DHX9 without Helicase Activity Activates Constitutive Expression of Nuclear Receptor Genes in Drosophila melanogaster.Doklady. Biochemistry and biophysics · 2025Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- MLE/DHX9 Helicase Activity Is Required to Regulate the Expression of a Number of Tissue-Specific Genes on Chromosome 4 in Drosophila melanogaster.Doklady. Biochemistry and biophysics · 2025Article
- A longitudinal analysis of function annotations of the human proteome reveals consistently high biases.Database : the journal of biological databases and curation · 2025Article
- DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders.Trends in genetics : TIG · 2025Review
- Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation.American journal of human genetics · 2025Article
- Article
- Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP.Neurogenetics · 2025Article
- Evolutionarily Conserved DHX9/MLE Helicase Is Involved in the Regulation of Its Own mRNA Expression Level in Drosophila melanogaster.Doklady. Biochemistry and biophysics · 2025Article
- DDX49 as a novel prognostic biomarker regulates colorectal cancer cell proliferation through the TIMM44-PI3K-AKT pathway.Frontiers in oncology · 2025Article
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- DDX3X syndrome: From clinical phenotypes to biological insights.Journal of neurochemistry · 2024Review
- DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.Nature communications · 2024Article
- MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.American journal of human genetics · 2024Article
- Biallelic variation in the choline and ethanolamine transportermedRxiv : the preprint server for health sciences · 2024Article
- The role of DEAD- and DExH-box RNA helicases in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2024Review
Corrections and comments
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Authors and funding
69 authors at 19 institutions in 10 countries.
Daniel G CalameSection of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Tianyu GuoSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China.
Chen WangSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China.
Lillian GarrettInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Angad JollyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
Moez DawoodDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Alina KurolapGenetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Noa Zunz HenigGenetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Jawid M FatihDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Isabella HermanSection of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Boys Town National Research Hospital, Boys Town, NE, USA.
Haowei DuDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Tadahiro MitaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Lore BeckerInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Birgit RathkolbInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Raffaele GerliniInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Claudia SeisenbergerInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Susan MarschallInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Jill V HunterDepartment of Radiology, Baylor College of Medicine, Houston, TX, USA; E.B. Singleton Department of Pediatric Radiology, Texas Children's Hospital, Houston, TX, USA.
Amanda GerardTexas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Alexis HeidlebaughAutism & Developmental Medicine Institute, Geisinger, Danville, PA, USA.
Thomas ChallmanAutism & Developmental Medicine Institute, Geisinger, Danville, PA, USA.
Rebecca C SpillmannDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Shalini N JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Zeynep Coban-AkdemirDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Seema LalaniTexas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Lingxiao LiuSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China.
Anya Revah-PolitiInstitute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Alejandro IglesiasDivision of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Edwin GuzmanDivision of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Evan BaughInstitute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Nathalie BoddaertPaediatric Radiology Department, AP-HP, Hôpital Necker Enfants Malades, Université Paris Cité, Institut Imagine INSERM U1163, 75015 Paris, France.
Sophie RondeauService de Médecine Génomique des Maladies Rares - APHP, Hôpital Necker Enfants Malades, Université de Paris, Paris, France.
Clothide OrmieresService de Médecine Génomique des Maladies Rares - APHP, Hôpital Necker Enfants Malades, Université de Paris, Paris, France.
Giulia BarciaService de Médecine Génomique des Maladies Rares - APHP, Hôpital Necker Enfants Malades, Université de Paris, Paris, France.
Queenie K G TanDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Isabelle ThiffaultGenomic Medicine Center, Children's Mercy Hospital, Kansas City, MO, USA.
Tomi PastinenGenomic Medicine Center, Children's Mercy Hospital, Kansas City, MO, USA; University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Kazim SheikhDepartment of Neurology, UT Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
Suur BilicilerDepartment of Neurology, UT Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
Davide MeiNeuroscience Department, Meyer Children's Hospital IRCCS, Florence, Italy.
Federico MelaniNeuroscience Department, Meyer Children's Hospital IRCCS, Florence, Italy.
Vandana ShashiDepartment of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA.
Yuval YaronGenetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Mary SteeleLifetime Neurodevelopmental Care, San Francisco, CA, USA.
Emma WakelingNorth East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Elsebet ØstergaardDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lusine Nazaryan-PetersenDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Undiagnosed Diseases Network
Francisca MillanGeneDx, Gaithersburg, MD, USA.
Teresa Santiago-SimGeneDx, Gaithersburg, MD, USA.
Julien ThevenonCentre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Fédération Hospitalo-Universitaire Médecine TRANSLationnelle et Anomalies du Développement, Centre Hospitalier Universitaire Dijon, Equipe Genetics of Developmental Anomalies-INSERM UMR 1231, Dijon, France.
Ange-Line BruelFunctional Unit for Diagnostic Innovation in Rare Diseases, FHU-TRANSLAD, Dijon Bourgogne University Hospital, Dijon, France; INSERM UMR1231 GAD "Génétique des Anomalies du Développement," FHU-TRANSLAD, University of Burgundy, Dijon, France.
Christel Thauvin-RobinetINSERM UMR1231 GAD "Génétique des Anomalies du Développement," FHU-TRANSLAD, University of Burgundy, Dijon, France; Department of Genetics and Reference Center for Development Disorders and Intellectual Disabilities, Dijon Bourgogne University Hospital, Dijon, France.
Denny PoppInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Pawel GawlinskiInstitute of Mother and Child, Kasprzaka 17a, 02-211 Warsaw, Poland.
Wojciech WiszniewskiOregon Health & Sciences University, 3181 SW Sam Jackson Park Road L103, Portland, OR, USA.
Dana MarafiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Davut PehlivanSection of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Richard A GibbsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Valerie Gailus-DurnerInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Renzo GuerriniNeuroscience Department, Meyer Children's Hospital IRCCS, Florence, Italy; University of Florence, Florence, Italy.
Helmut FuchsInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Martin Hrabě de AngelisInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; Chair of Experimental Genetics, TUM School of Life Sciences, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany.
Sabine M HölterInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Technische Universität München, Freising-Weihenstephan, Germany.
Hoi-Hung CheungSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China.
Shen GuSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China; Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China; Kunming Institute of Zoology Chinese Academy of Sciences, the Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong SAR, China. Electronic address: shengu@cuhk.edu.hk.
James R LupskiTexas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: jlupski@bcm.edu.
Baylor College of Medicine · USHelmholtz Zentrum München · DEChinese University of Hong Kong · HKHôpital Necker-Enfants Malades · FRColumbia University Irving Medical Center · USDuke Medical Center · USInserm · FRMeyer Children's Hospital · ITAutism & Developmental Medicine Institute · USChildren's Mercy Hospital · USLeipzig University · DETel Aviv Sourasky Medical Center · ILThe University of Texas Health Science Center at Houston · USUniversity of Copenhagen · DKColumbia University · USGreat Ormond Street Hospital for Children NHS Foundation Trust · GBNeuroDevelopment Center · USOregon Health & Science University · USTel Aviv University · IL
Funding
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MFrequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohortU01HG011758 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI RICHARD A GIBBS, JAMES R. LUPSKI · 2021 to 2026
$13.8MAn integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4MMEDICAL GENETICS RESEARCH FELLOWSHIP PROGRAMT32GM007526 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Brendan Lee · 1985 to 2026
$11.4MPreclinical and Clincial OutcomesP50HD103555 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI Sandesh Chakravarthy Sreenath Nagamani, David Loren Nelson · 2020 to 2026
$9.9MSTRUCTURAL VARIATION IN NEUROLOGICAL DISEASER35NS105078 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2018 to 2025
$6.0MMutidisciplinary Training;Brain Disorders &DevelopmentT32NS043124 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI SWANN, JOHN WILLIAM · 2002 to 2021
$4.6MAn integrated and diverse genomic medicine program for undiagnosed diseasesU01NS134350 · NINDS · DUKE UNIVERSITY · PI VANDANA SHASHI · 2023 to 2026
$3.6MEMERGING AND TROPICAL INFECTIOUS DISEASEST32AI007526 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI SOONG, LYNN · 1997 to 2025
$3.1MComprehensive Deep Phenotyping and Multi-omics to Develop Clinical and Molecular Biomarkers for MeCP2-related DiseasesK23NS125126 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Davut Pehlivan · 2022 to 2026
$1.1MIndividual genomic analyses to discover the molecular basis and mechanisms contributing to adult-onset diseaseK08HG008986 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI POSEY, JENNIFER ELLEN · 2017 to 2021
$831kNHGRI NIH HHS K08 HG008986NHGRI NIH HHS U01 HG007672NHGRI NIH HHS U01 HG011758NHGRI NIH HHS U54 HG003273NHGRI NIH HHS UM1 HG006542NIAID NIH HHS T32 AI007526NICHD NIH HHS P50 HD103555NIGMS NIH HHS T32 GM007526NINDS NIH HHS K23 NS125126NINDS NIH HHS R35 NS105078NINDS NIH HHS T32 NS043124NINDS NIH HHS U01 NS134350
Abstract
DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) analysis demonstrated genotype-phenotype correlations with LoF variants causing mild NDD phenotypes and nuclear localization signal (NLS) missense variants causing severe NDD. We investigated DHX9 variant-associated cellular phenotypes in human cell lines. Whereas wild-type DHX9 was restricted to the nucleus, NLS missense variants abnormally accumulated in the cytoplasm. Fibroblasts from an individual with an NLS variant also showed abnormal cytoplasmic DHX9 accumulation. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Two NDD-associated variants, p.Gly411Glu and p.Arg761Gln, altered DHX9 ATPase activity. The severe NDD-associated variant p.Arg141Gln did not affect DHX9 localization but instead increased R-loop levels and double-stranded DNA breaks. Dhx9
Indexed as
Charcot-Marie-Tooth DiseaseNeurodevelopmental DisordersAnimalsCell LineDEAD-box RNA HelicasesDichlorodiphenyl DichloroethyleneDNA HelicasesHumansMammalsMiceNeoplasm ProteinsDEAD-box RNA HelicasesDHX9 protein, humanDhx9 protein, mouseDichlorodiphenyl DichloroethyleneDNA HelicasesNeoplasm Proteinsallelic seriesCharcot-Marie-Tooth diseaseDExD/H-box RNA helicasesDHX9DNA damage repairepilepsyhomologous recombinationneurodevelopmental disordersneuropathyR-loops
Identifiers
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Registered trials
NCT02450851ClinicalTrials.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.