Evidence map›Paper›PMID 41720266›Full record

ArticleKidney international2026

Disruption of the human cystin-1 myristoyl-electrostatic switch causes polycystic kidney disease that phenocopies autosomal recessive polycystic kidney disease.

Chaozhe Yang, Naoe Harafuji, Jacob A Watts, Binli Tao, Claire Moran, Jenna Clements, Kalyn Price, Anthony Laucevicius, Natalie Burrill, Juliana Gebb and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Chaozhe YangCenter for Translational Science, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA; Center for Precision Medicine and Genomics Research, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA.
Naoe HarafujiCenter for Translational Science, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA; Center for Precision Medicine and Genomics Research, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA.
Jacob A WattsCenter for Translational Science, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA.
Binli TaoDepartment of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Claire MoranIntegrated Biomedical Sciences Program, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Jenna ClementsIntegrated Biomedical Sciences Program, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Kalyn PriceIntegrated Biomedical Sciences Program, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Anthony LauceviciusIntegrated Biomedical Sciences Program, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Natalie BurrillCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Juliana GebbCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Shelly SoniCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Edward OliverCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jill J SavlaCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Lori ChristCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Julie MoldenhauerCenter for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Erum A HartungDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Ryne DidierDepartment of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA.
Avni SantaniVeritas Genetics, Danvers, Massachusetts, USA.
Richard N SandfordAcademic Department of Genomic Medicine, University of Cambridge, Cambridge, UK.
Lisa SelkirkLuton and Dunstable University Hospital, Lutton, UK.
Jessica A RadleyNorth West Thames Regional Genetics Service, London, UK.
Kathy MannEast Genomic Laboratory Hub, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Ingrid SimonicovaEast Genomic Laboratory Hub, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Rudolfo KarlInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
Arsila Palliyulla Kariat AshrafInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
Dagmar WachtenInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
Landon WilsonDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Zsuzsanna BebokDepartment of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ljubica CaldovicCenter for Precision Medicine and Genomics Research, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA; Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia, USA.
Lisa M Guay-WoodfordCenter for Translational Science, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. Electronic address: guaywoodfl@chop.edu.

Funding

UAB Recessive PKD Research and Translational Core CenterP30DK074038 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MRUG, MICHAL · 2005 to 2019
$16.6M
UAB Childhood Cystic Kidney Disease Core Center (UAB-CCKDCC) - Therapeutic Development and Screening ResourceU54DK126087 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI John M Parant · 2020 to 2026
$6.7M
Cystin, a lipid raft and cilia-associated protein in PKDR01DK055534 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUAY-WOODFORD, LISA MARIE · 2000 to 2008
$2.5M
Decoding reno-protective mechanisms in mouse Pkhd1 models: Implications for ARPKD therapeuticsR01DK121530 · NIDDK · CHILDREN'S RESEARCH INSTITUTE · PI CALDOVIC, LJUBICA MORIZONO, GUAY-WOODFORD, LISA MARIE · 2020 to 2024
$1.9M
5500 Q-Trap Mass SpectrometerS10RR027822 · NCRR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARNES, STEPHEN · 2010 to 2010
$469k
NCRR NIH HHS S10 RR027822NIDDK NIH HHS P30 DK074038NIDDK NIH HHS R01 DK055534NIDDK NIH HHS R01 DK121530NIDDK NIH HHS U54 DK126087
6 · The paper itself

Abstract

introductionAutosomal recessive polycystic kidney disease (ARPKD) is caused primarily by pathogenic variants in PKHD1, encoding fibrocystin/polyductin. In Cys1

methodsTo study this, we utilized high-resolution ultrasound, array Comparative Genomic Hybridization and exon sequencing to identify an ARPKD-like kidney lesion and CYS1 defects in two families. Bioinformatic analyses compared cystin sequence conservation across mammals. Immunofluorescence, optogenetic studies, and 3D culture comparatively evaluated subcellular localization, ciliary trafficking, and cyst formation under cAMP stimulation of wild-type and mutant cystin. Tandem affinity purification/mass spectrometry identified cystin-binding partners. Serine-17 phosphorylation was evaluated functionally.

resultsThe Family 1 proband carried a homozygous deletion about 24-kb in size encompassing the CYS1 regulatory region and exon 1. In Family 2, two affected siblings had a homozygous CYS1 c.4G>A (p.Gly2Ser) variant affecting Gly2 within the N-terminal myristoylation motif. This region, together with an adjacent arginine-rich stretch flanked by serines-8 (S8) and -17 (S17) residues, comprises a conserved myristoyl-electrostatic switch that can regulate reversible protein-membrane binding. S17 phosphorylation modulates cystin membrane association and intracellular trafficking. In 3D culture, CRISPR/Cas9-generated cystin-null cells or null cells expressing cystin-1

conclusionsCystin-1 intracellular trafficking and function are regulated by a myristoyl-electrostatic switch mechanism. Cystic kidneys in three individuals with homozygous CYS1 pathogenic variants provide further support that cystin-1 deficiency causes polycystic kidney disease that phenocopies ARPKD.

Indexed as

KidneyPolycystic Kidney, Autosomal RecessiveAmino Acid Transport Systems, NeutralAnimalsCiliaComparative Genomic HybridizationFemaleHomozygoteHumansMalePedigreePhenotypePhosphorylationReceptors, Cell SurfaceAmino Acid Transport Systems, NeutralCTNS protein, humanPKHD1 protein, humanReceptors, Cell SurfaceARPKDcystincystin-1myristoyl-electrostatic switchPKA-phosphorylationPPM1A-dephosphorylation

Identifiers

PMID41720266
PMCPMC13056400

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Registered trials

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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.