Evidence map›Paper›PMID 36321451›Full record

ArticleCirculation2022

Pathogenesis of Cardiomyopathy Caused by Variants in

Radhika Agarwal, Hiroko Wakimoto, Joao A Paulo, Qi Zhang, Daniel Reichart, Christopher Toepfer, Arun Sharma, Angela C Tai, Mingyue Lun, Joshua Gorham and 4 more

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

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Review
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  10. Identification of novel and known variants inFrontiers in cardiovascular medicine · 2026
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  19. α Protein Kinase 3 Is Essential for Neonatal and Adult Cardiac Function.Journal of the American Heart Association · 2025
    Article
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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

14 authors at 4 institutions in 3 countries.

Radhika AgarwalDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Hiroko WakimotoDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0003-0225-6424
Joao A PauloDepartment of Cell Biology (J.A.P., S.P.G.), Harvard Medical School, Boston, MA.ORCID 0000-0002-4291-413X
Qi ZhangDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Daniel ReichartDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Christopher ToepferDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0003-4671-2030
Arun SharmaDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Angela C TaiDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Mingyue LunDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.
Joshua GorhamDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0001-5969-4690
Steven R DePalmaDepartment of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0002-0381-5016
Steven P Gygi *Department of Cell Biology (J.A.P., S.P.G.), Harvard Medical School, Boston, MA.
J G Seidman *Department of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0002-9082-3566
Christine E Seidman *Department of Genetics (R.A., H.W., Q.Z., D.R., C.T., A.S., A.C.T., M.L., J.G., S.R.D., J.G.S., C.E.S.), Harvard Medical School, Boston, MA.ORCID 0000-0001-6380-1209
Harvard University · USBrigham and Women's Hospital · USCedars-Sinai Medical Center · USCentre for Human Genetics · GB

Funding

Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
British Heart Foundation RE/18/3/34214NHLBI NIH HHS R01 HL080494Wellcome Trust 206466
6 · The paper itself

Abstract

background

methodsWe explored the putative kinase activity of ALPK3 and the consequences of damaging variants using isogenic human induced pluripotent stem cell-derived cardiomyocytes, mice, and human patient tissues.

resultsMultiple sequence alignment of all human α-kinase domains and their orthologs revealed 4 conserved residues that were variant only in ALPK3, demonstrating evolutionary divergence of the ALPK3 α-kinase domain sequence. Phosphoproteomic evaluation of both ALPK3 kinase domain inhibition and overexpression failed to detect significant changes in catalytic activity, establishing ALPK3 as a pseudokinase. Investigations into alternative functions revealed that ALPK3 colocalized with myomesin proteins (MYOM1, MYOM2) at both the nuclear envelope and the sarcomere M-band.

conclusionsALPK3 is an essential cardiac pseudokinase that inserts in the nuclear envelope and the sarcomere M-band. Loss of ALPK3 causes mislocalization of myomesins, critical force-buffering proteins in cardiomyocytes, and also dysregulates M-band proteins necessary for sarcomere protein turnover. We conclude that

Indexed as

CardiomyopathiesInduced Pluripotent Stem CellsMuscle ProteinsProtein KinasesAdultAnimalsChildConnectinHumansMiceMyocytes, CardiacSarcomeresAlpk3 protein, humanConnectinMuscle ProteinsProtein KinasescardiomyopathyhiPSC-CMM-bandphosphoproteomicspseudokinase, α-kinasesarcomere

Identifiers

PMID36321451
PMCPMC9698156
OpenAlexW4307975140

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.