ArticleAmerican journal of human genetics2018
Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.
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Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency.Circulation research · 2021Trial
- Mitochondrial dysfunction underlies cardiac contractility and growth defects in a zebrafish model ofbioRxiv : the preprint server for biology · 2026Article
- Melatonin promotes stomatal immunity by mediating phytohormone crosstalk inFrontiers in plant science · 2026Article
- Nonsense-mediated mRNA decay and associated splicing patterns in neurodevelopmental disorders.Frontiers in molecular biosciences · 2026Review
- Neuroanatomical features of NAA10 and NAA15-related neurodevelopmental syndromes.Journal of neuroradiology = Journal de neuroradiologie · 2025Article
- Natural History of NAA15 -Related Neurodevelopmental Disorder Through Adolescence.American journal of medical genetics. Part A · 2025Article
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- Exome sequencing in Nigerian children with early-onset epilepsy syndromes.Epilepsia open · 2025Article
- Illuminating the impact of N-terminal acetylation: from protein to physiology.Nature communications · 2025Review
- Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses.NPJ genomic medicine · 2024Article
- A repository of Ogden syndrome patient derived iPSC lines and isogenic pairs by X-chromosome screening and genome-editing.bioRxiv : the preprint server for biology · 2024Article
- Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.American journal of medical genetics. Part A · 2024Article
- Diverging co-translational protein complex assembly pathways are governed by interface energy distribution.Nature communications · 2024Article
- Longitudinal Adaptive Behavioral Outcomes in Ogden Syndrome by Seizure Status and Therapeutic Intervention.medRxiv : the preprint server for health sciences · 2024Article
- Evaluating possible maternal effect lethality and genetic background effects inbioRxiv : the preprint server for biology · 2024Article
- Genome Sequencing of Idiopathic Speech Delay.Human mutation · 2024Article
- Molecular diagnosis of patients with syndromic short stature identified by trio whole-exome sequencing.Frontiers in genetics · 2024Article
- Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024Article
- Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.PloS one · 2024Article
- Clinical exome sequencing efficacy and phenotypic expansions involving anomalous pulmonary venous return.European journal of human genetics : EJHG · 2023Article
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Authors and funding
72 authors at 20 institutions in 9 countries.
Hanyin ChengBaylor Genetics, Houston, TX, 77021, USA.
Avinash V DharmadhikariBaylor Genetics, Houston, TX, 77021, USA.
Sylvia VarlandDepartment of Biomedicine, University of Bergen, N-5020 Bergen, Norway; Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway.
Ning MaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Deepti DomingoSchool of Biological Sciences, Faculty of Genes and Evolution, the University of Adelaide, Adelaide, SA 5000, Australia.
Robert KleynerStanley Institute for Cognitive Genomics, 1Bungtown Road, Cold Spring Harbor Laboratory, NY 11724, USA.
Alan F RopeDepartment of Medical Genetics, Kaiser Permanente Northwest, Portland, OR 97227, USA.
Margaret YoonStanley Institute for Cognitive Genomics, 1Bungtown Road, Cold Spring Harbor Laboratory, NY 11724, USA.
Asbjørg Stray-PedersenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, N-0424 Oslo, and Institute of Clinical Medicine, University of Oslo, N-0318 Oslo, Norway.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Sarah R CrewsDepartment of Pharmacology, Creighton University Medical School, Omaha, NE, 68178, USA.
Mohammad K EldomeryDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zeynep Coban AkdemirDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Andrea M LewisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.
Vernon R SuttonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Erin ConboyDepartment of Clinical Genomics, Mayo Clinic, MN 55905, USA.
Katherine AgreDepartment of Clinical Genomics, Mayo Clinic, MN 55905, USA.
Fan XiaBaylor Genetics, Houston, TX, 77021, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Magdalena WalkiewiczBaylor Genetics, Houston, TX, 77021, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; The National Institute of Allergy and Infectious Disease, The National Institutes of Health, Bethesda, MD 20892, USA.
Mauro LongoniPediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
Frances A HighPediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
Marjon A van SlegtenhorstDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands.
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands.
Candice R FinnilaHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
Arie van HaeringenDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2333, The Netherlands.
Nicolette den HollanderDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2333, The Netherlands.
Claudia RuivenkampDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2333, The Netherlands.
Sakkubai NaiduKennedy Krieger Institute, 801 North Broadway Baltimore, MD 21205, USA.
Sonal MahidaKennedy Krieger Institute, 801 North Broadway Baltimore, MD 21205, USA.
Elizabeth E PalmerGenetics of Learning Disability Service, Hunter Genetics, Waratah, NSW 2298, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2031, Australia.
Lucinda MurrayGenetics of Learning Disability Service, Hunter Genetics, Waratah, NSW 2298, Australia.
Derek LimWest Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Mindelsohn Way, Birmingham B15 2TG, UK.
Parul JayakarDivision of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL 33155, USA.
Michael J ParkerSheffield Clinical Genetics Service, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK.
Stefania GiustoOasi Research Institute - Istituto di Ricovero e Cura a Carattere Scientifico, Troina 94018, Italy.
Emanuela StracuzziOasi Research Institute - Istituto di Ricovero e Cura a Carattere Scientifico, Troina 94018, Italy.
Corrado RomanoOasi Research Institute - Istituto di Ricovero e Cura a Carattere Scientifico, Troina 94018, Italy.
Jennifer S BeighleyDepartment of Psychiatry, University of Washington, Seattle WA, 98195, USA.
Raphael A BernierDepartment of Psychiatry, University of Washington, Seattle WA, 98195, USA.
Sébastien KüryDepartment of Medical Genetics, Centre Hospitalier Universitaire, Nantes 44093, France.
Mathilde NizonDepartment of Medical Genetics, Centre Hospitalier Universitaire, Nantes 44093, France.
Mark A CorbettAdelaide Medical School and Robinson Research Institute, the University of Adelaide, Adelaide, SA 5000, Australia.
Marie ShawAdelaide Medical School and Robinson Research Institute, the University of Adelaide, Adelaide, SA 5000, Australia.
Alison GardnerAdelaide Medical School and Robinson Research Institute, the University of Adelaide, Adelaide, SA 5000, Australia.
Christopher BarnettPaediatric and Reproductive Genetics, South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), Adelaide, SA 5006, Australia.
Ruth ArmstrongEast Anglian Medical Genetics Service, Clinical Genetics, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Karin S KassahnDepartment of Genetics and Molecular Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, SA 5006, Australia; School of Biological Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Anke Van DijckDepartment of Medical Genetics, University of Antwerp, Antwerp 2000, Belgium.
Geert VandeweyerDepartment of Medical Genetics, University of Antwerp, Antwerp 2000, Belgium.
Tjitske KleefstraDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.
Jolanda SchievingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.
Marjolijn J JongmansDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.
Bert B A de VriesDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.
Rolph PfundtDepartment of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.
Bronwyn KerrManchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9PL, UK; Division of Evolution and Genomic Sciences School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.
Samantha K RojasChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Kym M BoycottChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Richard PersonGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Rebecca WillaertGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
R Frank KooyDepartment of Medical Genetics, University of Antwerp, Antwerp 2000, Belgium.
Yaping YangBaylor Genetics, Houston, TX, 77021, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX 77030, USA.
Thomas ArnesenDepartment of Biomedicine, University of Bergen, N-5020 Bergen, Norway; Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway; Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
Gregory M CooperHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Jozef GeczSchool of Biological Sciences, Faculty of Genes and Evolution, the University of Adelaide, Adelaide, SA 5000, Australia; Adelaide Medical School and Robinson Research Institute, the University of Adelaide, Adelaide, SA 5000, Australia; Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Holly A F StessmanDepartment of Pharmacology, Creighton University Medical School, Omaha, NE, 68178, USA.
Linyan MengBaylor Genetics, Houston, TX, 77021, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: lmeng@bcm.edu.
Gholson J LyonStanley Institute for Cognitive Genomics, 1Bungtown Road, Cold Spring Harbor Laboratory, NY 11724, USA. Electronic address: gholsonjlyon@gmail.com.
Baylor College of Medicine · USBaylor Genetics · USUniversity of Adelaide · AUCold Spring Harbor Laboratory · USLeiden University Medical Center · NLOasi Maria SS · ITRadboud University Medical Center · NLUniversity of Antwerp · BEUniversity of Washington · USCentre Hospitalier Universitaire de Nantes · FRCreighton University · USErasmus MC · NLHudsonAlpha Institute for Biotechnology · USKennedy Krieger Institute · USMayo Clinic in Florida · USRadboud University Nijmegen · NLSouth Australia Pathology · AUAddenbrooke's Hospital · GBBirmingham Women’s and Children’s NHS Foundation Trust · GBCardiovascular Institute of the South · US
Funding
THE DROSOPHILA GENETICS AND RNAI CORE (THE FLY CORE)P01HD068250 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, WENDY K, DONAHOE, PATRICIA K · 2011 to 2022
$17.1MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MSouth-seq: DNA sequencing for newborn nurseries in the SouthU01HG007301 · NHGRI · HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY · PI BARSH, GREGORY STEFAN, COOPER, GREGORY MICHAEL · 2017 to 2021
$11.9MSporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2MIntellectual and Developmental Disabilities Research CenterU54HD083091 · NICHD · UNIVERSITY OF WASHINGTON · PI GURALNICK, MICHAEL J · 2014 to 2019
$7.9MGenomic Diagnosis in Children with Developmental DelayUM1HG007301 · NHGRI · HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY · PI COOPER, GREGORY MICHAEL, MYERS, RICHARD M · 2013 to 2016
$7.5MAmino-terminal acetylation of proteins in mammalian biology and diseaseR35GM133408 · NIGMS · INSTITUTE FOR BASIC RES IN DEV DISABIL · PI LYON, GHOLSON · 2019 to 2023
$2.4MIndividual 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 HG007301NHGRI NIH HHS UM1 HG006542NHGRI NIH HHS UM1 HG007301NICHD NIH HHS P01 HD068250NICHD NIH HHS U54 HD083091NIGMS NIH HHS R35 GM133408NIMH NIH HHS R01 MH101221Wellcome Trust
Abstract
N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development.
Indexed as
Genetic Predisposition to DiseaseGenetic VariationAbnormalities, MultipleAdolescentAdultAutism Spectrum DisorderCell LineChildExonsFemaleGene Expression RegulationHumansIntellectual DisabilityMaleMiddle AgedMutationNAA15 protein, humanN-Terminal Acetyltransferase AN-Terminal Acetyltransferase ERNA, Messengerautismcongenital heart defectsintellectual disabilityNAA10NAA15NatA complexneurodevelopmental disorderN-terminal acetylation (NTA)N-terminal acetyltransferases (NATs)Ogden syndrome
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