ArticleNature genetics2015
COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.
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In one paragraph
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 225 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
225citing papers in PubMed, 2 pooled it
11.3field-weighted citation impact, top 1% 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.
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Who cites it
225 citing papers in PubMed, 2 syntheses or guidelines pooled it, 389 citations in OpenAlex.
- Guideline
- Altered gene expression and PTSD symptom dimensions in World Trade Center responders.Molecular psychiatry · 2022Pooled it
- Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features.Journal of medical genetics · 2019Trial
- A systems perspective on monoallelic inborn errors of immunity.Nature genetics · 2026Review
- Remaking an exit: dynamic regulation of ER exit sites by post-translational modifications.Trends in cell biology · 2026Review
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- COPI Coatomer Regulates Several Steps of HDL Metabolism.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Rare variant analysis of whole genome sequenced juvenile idiopathic arthritis multiplex pedigrees identifies rare variants in NOD2 and ACVR1.G3 (Bethesda, Md.) · 2026Article
- Imaging findings in pediatric interferonopathies.Pediatric radiology · 2026Review
- COPZ1 depletion induces cell death through different mechanisms in in vitro murine models of thyroid cancer.European thyroid journal · 2026Article
- Distinct roles of COPI proteins attenuated in cell senescence.Science advances · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- The COPI coatomer influences LDL receptor activity, hepatic lipid storage, and apoB secretion.bioRxiv : the preprint server for biology · 2026Article
- Interstitial lung disease and the STING pathway.The Journal of clinical investigation · 2026Review
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Recurrent COPA mutation drives R-spondin-independent Wnt activation in intestinal tumors.Nature genetics · 2026Article
- Cell autonomous inflammation in VEXAS is mediated by cGAS-STING.bioRxiv : the preprint server for biology · 2026Article
- Childhood Interstitial Lung Disease-Successful Application of a Stepwise Diagnostic Classification.Journal of clinical medicine · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- The STING HAQ haplotype and clinical non-penetrance in COPA syndrome.The Journal of experimental medicine · 2026Article
165 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors at 5 institutions in 2 countries.
Levi B Watkin1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Birthe JessenDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Wojciech WiszniewskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Timothy J VeceDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Max JanDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Youbao ShaDepartment of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Maike ThamsenDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Regie L P Santos-CortezCenter for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USA.
Kwanghyuk LeeCenter for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USA.
Tomasz GambinDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Lisa R Forbes1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Christopher S LawDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Asbjørg Stray-Pedersen1] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA. [2] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Mickie H ChengDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Emily M Mace1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Mark S AndersonDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Dongfang Liu1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Ling Fung TangCardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
Sarah K Nicholas1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Karen Nahmod1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
George Makedonas1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Debra L Canter1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Pui-Yan Kwok1] Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA. [2] Department of Dermatology, University of California, San Francisco, San Francisco, California, USA.
John HicksDepartment of Pathology, Texas Children's Hospital, Houston, Texas, USA.
Kirk D JonesDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Samantha PenneyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Shalini N JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Michael D RosenblumDepartment of Dermatology, University of California, San Francisco, San Francisco, California, USA.
Sharon D DellDivision of Respiratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
Michael R WaterfieldDepartment of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Feroz R PapaDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Donna M MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Noah ZaitlenDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Suzanne M LealCenter for Statistical Genetics, Baylor College of Medicine, Houston, Texas, USA.
Claudia Gonzaga-JaureguiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Baylor-Hopkins Center for Mendelian Genomics
Eric Boerwinkle1] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. [2] Human Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, Texas, USA.
N Tony EissaDepartment of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Richard A Gibbs1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
James R Lupski1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [3] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Jordan S Orange1] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. [2] Texas Children's Hospital Center for Human Immuno-Biology, Houston, Texas, USA.
Anthony K Shum1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USBaylor College of Medicine · USTexas Children's Hospital · USBaylor Genetics · USHospital for Sick Children · CA
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 GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6MNonrecurrent rearrangements, genome architecture and neurodegenerative disease.R01NS058529 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2009 to 2017
$5.0MDirecting Function at the Natural Killer Cell Secretory Immunological SynapseR01AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ORANGE, JORDAN SCOTT · 2007 to 2019
$4.8MThe adaptor protein Crk in immune responsesR01AI130197 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Dongfang Liu · 2018 to 2026
$4.2MImmunology Scientist Training ProgramT32AI053831 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B · 2003 to 2018
$4.2MTranslational studies of autoimmune-mediated lung diseaseR01HL122533 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHUM, ANTHONY · 2015 to 2019
$1.9MDirecting Function at the Natural Killer Cell Secretory Immunological SynapseR37AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jordan Scott Orange · 2024 to 2026
$1.5MThe adaptor protein Crk in immune responsesR56AI130197 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI LIU, DONGFANG · 2017 to 2023
$874kRicher Models of Asthma Risk: Bridging the Environment-Genetics DivideK25HL121295 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZAITLEN, NOAH A · 2014 to 2018
$784kGenome analysis to elucidate molecular mechanisms for peripheral neuropathiesK23NS078056 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI WISZNIEWSKI, WOJCIECH KRZYSZTOF · 2012 to 2016
$783kMechanisms of immune regulation in the skinK08AR062064 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENBLUM, MICHAEL DAVID · 2012 to 2016
$670kNHGRI NIH HHS U54HG003273NHGRI NIH HHS U54 HG006542NHGRI NIH HHS U54HG006542NHLBI NIH HHS K08 HL095659NHLBI NIH HHS K08HL095659NHLBI NIH HHS K25 HL121295NHLBI NIH HHS L30 HL098006NHLBI NIH HHS R01 HL122533NIAID NIH HHS AI053831NIAID NIH HHS R01 AI067946NIAID NIH HHS R01AI067946NIAID NIH HHS R01 AI130197NIAID NIH HHS R21 AI124769NIAID NIH HHS R21 AI129594NIAID NIH HHS R37 AI067946NIAID NIH HHS T32 AI053831NIAMS NIH HHS K08 AR062064NINDS NIH HHS 2R01NS058529NINDS NIH HHS K23 NS078056NINDS NIH HHS K23NS078056NINDS NIH HHS R01 NS058529
Abstract
Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. Additionally, expression of mutant COPA results in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4(+) T cells also demonstrate significant skewing toward a TH17 phenotype that is implicated in autoimmunity. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease.
Indexed as
Amino Acid SequenceArthritisAutoimmune DiseasesChild, PreschoolCoatomer ProteinEndoplasmic ReticulumEndoplasmic Reticulum StressFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGolgi ApparatusHEK293 CellsHumansInfantLod ScoreLung Diseases, InterstitialCoatomer Protein
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