Evidence map›Paper›PMID 41636844›Full record

ArticleAngiogenesis2026

Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q-driven capillary malformations.

Tong Xu, Vera Janssen, Nathalie R Reinhard, Paula Sobrevals-Alcaraz, Robert M van Es, Annett de Haan, Julian de Swart, Martijn Wehrens, Hannah de Kraker, Albert Wolkerstorfer and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angiogenesis, 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

13 authors.

Tong XuDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Vera JanssenDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Nathalie R ReinhardDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Paula Sobrevals-AlcarazCenter for Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands.
Robert M van EsCenter for Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands.
Annett de HaanDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Julian de SwartSwammerdam Institute for Life Sciences, Section of Molecular Cytology, van Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, Sciencepark 904, 1098 XH, Amsterdam, The Netherlands.
Martijn WehrensSwammerdam Institute for Life Sciences, Section of Molecular Cytology, van Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, Sciencepark 904, 1098 XH, Amsterdam, The Netherlands.
Hannah de KrakerDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Albert WolkerstorferDepartment of Dermatology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Chantal M A M van der HorstDepartment of Plastic, Reconstructive, and Hand Surgery, Amsterdam Cardiovascular Sciences, Amsterdam Public Health, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Harmjan R VosCenter for Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands.
Stephan HuveneersDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. s.huveneers@amsterdamumc.nl.

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek era4healthcvd-122Nederlandse Organisatie voor Wetenschappelijk Onderzoek NWO OCENW.KLEIN.281
6 · The paper itself

Abstract

Capillary malformations (CMs) are congenital vascular lesions caused by somatic mutations in the GNAQ gene, most frequently resulting in a p.R183Q substitution in the Gαq protein in endothelial cells. However, the downstream signaling pathways by which Gαq-R183Q impairs vascular function remain poorly defined. To address this, we generated human dermal endothelial cells lacking endogenous Gαq and expressing the Gαq-R183Q mutant. Next, using SILAC-based quantitative proteomics, we mapped the Gαq-R183Q-induced endothelial phosphoproteome. These analyses identified aberrant activation of the Calcineurin-NFAT-DSCR1.4 signaling cascade as a key pathogenic feature. NFAT dysregulation and DSCR1 expression in endothelial cells were confirmed in patient-derived biopsies. Pharmacological inhibition of Calcineurin with tacrolimus partially normalized NFAT signaling in Gαq-R183Q endothelial cells. Strikingly, genetic depletion of DSCR1 in Gαq-R183Q cells fully restored Calcineurin/NFAT signaling and enabled proper endothelial migration and angiogenic sprouting, highlighting DSCR1 as a critical effector of Gαq-R183Q signaling in CMs. These findings reveal a druggable signaling circuit downstream of Gαq-R183Q that may serve as a foundation for future therapies targeting GNAQ-driven vascular malformations, including Sturge-Weber syndrome.

Indexed as

CalcineurinCapillariesGTP-Binding Protein alpha Subunits, Gq-G11Intracellular Signaling Peptides and ProteinsMuscle ProteinsNFATC Transcription FactorsSignal TransductionDNA-Binding ProteinsEndothelial CellsHumansMutationTacrolimusCalcineurinDNA-Binding ProteinsGNAQ protein, humanGTP-Binding Protein alpha Subunits, Gq-G11Intracellular Signaling Peptides and ProteinsMuscle ProteinsNFATC Transcription FactorsRCAN1 protein, humanTacrolimusAngiogenesisEndothelial cellFK506GNAQ p.R183QMigrationSturge-Weber syndromeTacrolimusVascular malformation

Identifiers

PMID41636844
PMCPMC12872783

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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.