Evidence map›Paper›PMID 30571258›Full record

ArticleCirculation2018

Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor Hyperphosphorylation.

Wengen Zhu, Cen Wang, Jinzhu Hu, Rong Wan, Jianhua Yu, Jinyan Xie, Jianyong Ma, Linjuan Guo, Jin Ge, Yumin Qiu and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 14% of its field
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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Longitudinal Characterization of GiantResearch (Washington, D.C.) · 2026
    Article
  3. Reappraisal ofReviews in cardiovascular medicine · 2025
    Review
  4. Article
  5. Loss of protein phosphatase 2A regulatory subunitFrontiers in cardiovascular medicine · 2024
    Article
  6. Human leukocyte antigen F-associated transcript 10 regulates thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  7. Role of CaArchives of toxicology · 2023
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. 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

20 authors at 3 institutions in 3 countries.

Wengen ZhuDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Cen WangDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jinzhu HuDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Rong WanJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jianhua YuDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jinyan XieJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jianyong MaDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Linjuan GuoDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jin GeDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Yumin QiuDepartment of General Surgery (Y.Q., L.C.), Second Affiliated Hospital of Nanchang University, China.
Leifeng ChenDepartment of General Surgery (Y.Q., L.C.), Second Affiliated Hospital of Nanchang University, China.
Hualong LiuDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Xia YanJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Xiuxia LiuJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Jin YeHefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui (J.Y., C.W.).
Wenfeng HeJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Yang ShenJiangxi Key Laboratory of Molecular Medicine (R.W., J.X., X.Y., X.L., W.H., Y.S., K.H.), Second Affiliated Hospital of Nanchang University, China.
Chao WangHefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui (J.Y., C.W.).
Peter J MohlerDepartment of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, College of Medicine, The Dorothy M. Davis Heart and Lung Research Institute, Departments of Physiology and Cell Biology and Internal Medicine, Columbus (P.J.M.).
Kui HongDepartment of Cardiovascular Medicine (W.Z., C.W., J.H., J.Y., J.M., L.G., J.G., H.L., K.H.), Second Affiliated Hospital of Nanchang University, China.
Nanchang University · CNHefei National Center for Physical Sciences at Nanoscale · CNThe Ohio State University Wexner Medical Center · US

Funding

Defining novel mechanisms for human arrhythmiaR35HL135754 · NHLBI · OHIO STATE UNIVERSITY · PI MOHLER, PETER J. · 2017 to 2023
$6.0M
Role of spectrin/ankyrin-G complex in myocyte signaling and cardiac excitabilityR01HL083422 · NHLBI · VANDERBILT UNIVERSITY · PI MOHLER, PETER J. · 2006 to 2016
$3.8M
Defining novel mechanisms for regulation of atrial INa and arrhythmiasR01HL134824 · NHLBI · OHIO STATE UNIVERSITY · PI HUND, THOMAS JEFFREY, MOHLER, PETER J. · 2017 to 2020
$3.0M
NHLBI NIH HHS R01 HL083422NHLBI NIH HHS R01 HL134824NHLBI NIH HHS R35 HL135754
6 · The paper itself

Abstract

backgroundHuman loss-of-function variants of ANK2 (ankyrin-B) are linked to arrhythmias and sudden cardiac death. However, their in vivo effects and specific arrhythmogenic pathways have not been fully elucidated.

methodsWe identified new ANK2 variants in 25 unrelated Han Chinese probands with ventricular tachycardia by whole-exome sequencing. The potential pathogenic variants were validated by Sanger sequencing. We performed functional and mechanistic experiments in ankyrin-B knockin (KI) mouse models and in single myocytes isolated from KI hearts.

resultsWe detected a rare, heterozygous ANK2 variant (p.Q1283H) in a proband with recurrent ventricular tachycardia. This variant was localized to the ZU5

conclusionsANK2 p.Q1283H is a disease-associated variant that confers susceptibility to stress-induced arrhythmias, which may be prevented by the administration of metoprolol or flecainide. This variant is associated with the loss of protein phosphatase 2A activity, increased phosphorylation of ryanodine receptor, exaggerated delayed afterdepolarization-mediated trigger activity, and arrhythmogenesis.

Indexed as

Action PotentialsAnimalsAnkyrinsArrhythmias, CardiacCalciumDisease Models, AnimalElectrocardiographyFemaleHumansIsoproterenolMiceMiddle AgedMyocytes, CardiacPhosphorylationPolymorphism, Single NucleotideProtein Phosphatase 2ANK2 protein, humanAnkyrinsCalciumIsoproterenolProtein Phosphatase 2RyanodineRyanodine Receptor Calcium Release Channelankyrin-Barrhythmiacatecholamineprotein phosphatase 2Aryanodine receptorvariant

Identifiers

PMID30571258
PMCPMC6276866
OpenAlexW2889597730

What OpenQuestion holds

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Registered trials

None linked

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.