ArticleNature genetics2015
Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137citing papers in PubMed
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Who cites it
137 citing papers in PubMed, 212 citations in OpenAlex.
- Multiexon deletion alleles of ATF6 linked to achromatopsia.JCI insight · 2020Trial
- REPEATABILITY AND LONGITUDINAL ASSESSMENT OF FOVEAL CONE STRUCTURE IN CNGB3-ASSOCIATED ACHROMATOPSIA.Retina (Philadelphia, Pa.) · 2017Trial
- Review
- Single-Nucleus RNA Sequencing Highlights Endothelial and Müller Cell ER Stress During Retinal Neovascularization in Vldlr-/- Mouse.Investigative ophthalmology & visual science · 2026Article
- Loss of BAP31 Is Detrimentally Aging Photoreceptors Through ER Stress-Mediated Retinal Degeneration.Cells · 2025Article
- Targeting ATF6 reduces pathological neovascularization and improves visual outcomes in retinal disease models.Scientific reports · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.Biochemical Society transactions · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- A deafness-blindness syndrome results from ATF6-based disruption of the unfolded protein response.The Journal of clinical investigation · 2025Article
- Mutations in unfolded protein response regulator ATF6 cause hearing and vision loss syndrome.The Journal of clinical investigation · 2025Article
- Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.Molecular vision · 2025Review
- Dysregulation of Retinal and Photoreceptor Structural Integrity Genes in ATF6Advances in experimental medicine and biology · 2025Article
- Vulnerability of the NrlAdvances in experimental medicine and biology · 2025Article
- Targeting the self-amplifying loop between ATF6 and SNAI1 to inhibit epithelial‒mesenchymal transition in fibrotic lesions.Theranostics · 2025Article
- Infantile Nystagmus Syndrome-Associated Inherited Retinal Diseases: Perspectives from Gene Therapy Clinical Trials.Life (Basel, Switzerland) · 2024Review
- Microperimetry Sensitivity Correlates to Structural Macular Changes in Adolescents with Achromatopsia Unlike Other Visual Function Tests.Journal of clinical medicine · 2024Article
- S-cone contribution to oscillatory potentials in patients with blue cone monochromacy.Documenta ophthalmologica. Advances in ophthalmology · 2024Article
- Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia.BMC medical genomics · 2024Article
- Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 14 institutions in 5 countries.
Susanne KohlInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Ditta ZoborInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Wei-Chieh ChiangDepartment of Pathology, University of California, San Diego, La Jolla, California, USA.
Nicole WeisschuhInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Jennifer StallerInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Irene Gonzalez MenendezInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Stanley Chang1] Department of Ophthalmology, Columbia University, New York, New York, USA. [2] Edward Harkness Eye Institute, New York Presbyterian Hospital, New York, New York, USA.
Susanne C BeckInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Marina Garcia GarridoInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Vithiyanjali SothilingamInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Mathias W SeeligerInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Franco StanzialClinical Genetics Service, Regional Hospital Bozen, Bozen, Italy.
Francesco BenedicentiClinical Genetics Service, Regional Hospital Bozen, Bozen, Italy.
Francesca InzanaClinical Genetics Service, Regional Hospital Bozen, Bozen, Italy.
Elise HéonDepartment of Ophthalmology and Vision Sciences, Programme of Genetics and Genomic Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Ajoy VincentDepartment of Ophthalmology and Vision Sciences, Programme of Genetics and Genomic Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.ORCID 0000000164463846
Jill BeisMedical Genetics, IWK Health Centre, Halifax, Nova Scotia, Canada.
Tim M Strom1] Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany. [2] Institute of Human Genetics, Technische Universität München, Munich, Germany.
Günther RudolphUniversity Eye Hospital, Ludwig Maximilians University, Munich, Germany.
Susanne RoosingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Anneke I den Hollander1] Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. [2] Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Frans P M CremersDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Irma LopezMcGill Ocular Genetics Centre, McGill University Health Centre, Montreal, Quebec, Canada.
Huanan RenMcGill Ocular Genetics Centre, McGill University Health Centre, Montreal, Quebec, Canada.
Anthony T Moore1] University College London Institute of Ophthalmology, University College London, London, UK. [2] Moorfields Eye Hospital, London, UK. [3] Ophthalmology Department, University of California San Francisco Medical School, San Francisco, California, USA.
Andrew R Webster1] University College London Institute of Ophthalmology, University College London, London, UK. [2] Moorfields Eye Hospital, London, UK.
Michel Michaelides1] University College London Institute of Ophthalmology, University College London, London, UK. [2] Moorfields Eye Hospital, London, UK.
Robert K KoenekoopMcGill Ocular Genetics Centre, McGill University Health Centre, Montreal, Quebec, Canada.
Eberhart Zrenner1] Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. [2] Werner Reichardt Center for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
Randal J KaufmanDegenerative Diseases Program, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
Stephen H Tsang1] Department of Ophthalmology, Columbia University, New York, New York, USA. [2] Jonas Laboratory of Stem Cell and Regenerative Medicine, Columbia University, New York, New York, USA. [3] Brown Glaucoma Laboratory, Columbia University, New York, New York, USA. [4] Institute of Human Nutrition, Columbia University, New York, New York, USA. [5] Department of Pathology and Cell Biology, Columbia University, New York, New York, USA.
Bernd WissingerInstitute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
Jonathan H Lin1] Department of Pathology, University of California, San Diego, La Jolla, California, USA. [2] Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA.
STZ eyetrial · DEMcGill University Health Centre · CARadboud University Nijmegen · NLMoorfields Eye Hospital NHS Foundation Trust · GBUniversity of California San Diego · USUniversity of Toronto · CABernstein Center for Computational Neuroscience Tübingen · DEColumbia University · USHelmholtz Zentrum München · DEIzaak Walton Killam Health Centre · CALudwig-Maximilians-Universität München · DENewYork–Presbyterian Hospital · USSanford Burnham Prebys Medical Discovery Institute · USUniversity College Hospital · GB
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Parisa Tehranifar · 1985 to 2026
$115.3MInstrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.9MCELLULAR MECHANISMS OF INHERITED RETINAL DEGENERATIONR01EY001919 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAVAIL, MATTHEW M · 1985 to 2014
$8.3MToward mechanism- and gene-based therapies for retinal degenerationR01EY018213 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen H Tsang · 2008 to 2026
$6.6MRegulation of Factor VIII SecretionR01HL052173 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 1995 to 2014
$6.5MRole of the Unfolded Protein Response in Beta CellR37DK042394 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2007 to 2016
$4.9MRegulation of ER stress-induced cell deathR01DK088227 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2010 to 2014
$3.1MProtein Homeostasis and Proteotoxicity MechanismsR01NS088485 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LIN, JONATHAN · 2015 to 2024
$3.0MEndoplasmic Reticulum Stress in Retinal DegenerationR01EY020846 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LIN, JONATHAN · 2010 to 2014
$1.9MUnfolded Protein Response in Glucose HomeostasisR01DK042394 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAUFMAN, RANDAL J. · 2003 to 2006
$1.2MCELLULAR MECHANISMS OF INHERITED RETINAL DEGENERATIONR37EY001919 · NEI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI LAVAIL, MATTHEW M · 1989 to 1998
–Cellular and Molecular Mechanisms of Age-Related Retinal DegenerationI01BX002284 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI LIN, JONATHAN · 2014 to 2023
–BLRD VA I01 BX002284NCI NIH HHS 5P30CA013696NCI NIH HHS P30 CA013696NEI NIH HHS 5P30EY019007NEI NIH HHS EY001919NEI NIH HHS EY020846NEI NIH HHS P30 EY019007NEI NIH HHS R01 EY001919NEI NIH HHS R01 EY018213NEI NIH HHS R01EY018213NEI NIH HHS R01 EY020846NHLBI NIH HHS HL052173NHLBI NIH HHS R01 HL052173NIDDK NIH HHS DK042394NIDDK NIH HHS DK088227NIDDK NIH HHS R01 DK042394NIDDK NIH HHS R01 DK088227NIDDK NIH HHS R37 DK042394NINDS NIH HHS R01 NS088485Wellcome TrustWellcome Trust 099173/Z/12/Z
Abstract
Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozygous mutations in the ATF6 gene (encoding activating transcription factor 6A), a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. Patients had evidence of foveal hypoplasia and disruption of the cone photoreceptor layer. The ACHM-associated ATF6 mutations attenuate ATF6 transcriptional activity in response to ER stress. Atf6(-/-) mice have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age. This new ACHM-related gene suggests a crucial and unexpected role for ATF6A in human foveal development and cone function and adds to the list of genes that, despite ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype.
Indexed as
Activating Transcription Factor 6AdolescentAdultAged, 80 and overAnimalsChildColor Vision DefectsFemaleGenetic Association StudiesHEK293 CellsHumansMaleMice, Inbred C57BLMice, KnockoutMiddle AgedMutation, MissenseActivating Transcription Factor 6ATF6 protein, human
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