Evidence map›Paper›PMID 40879463›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2025

Functional and Structural Characterization of LRRK2 p.V1447L in Parkinson's Disease.

Neringa Pratuseviciute, Pawel Lis, Sacha Weber, Nicolas Gruchy, Lionel Arnaud, Dario R Alessi, Esther Sammler

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. medRxiv : the preprint server for health sciences · 2026
    Article
  3. Ex Vivo LRRK2 Activation in Asian G2385R and R1628P Variant Carriers and Idiopathic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  4. Large-scale functional annotation establishes a reference framework for humanmedRxiv : the preprint server for health sciences · 2026
    Article
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

7 authors.

Neringa PratuseviciuteMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Pawel LisMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.ORCID https://orcid.org/0000-0002-4978-7671
Sacha WeberInstitut du Cerveau-Paris Brain Institute ICM, Sorbonne Université, Inserm 1127, CNRS 7225, Hôpital de la Pitié Salpêtrière, Paris, France.
Nicolas GruchyUniversité Caen Normandie, Normandie Université, Biotargen UR7450, CHU de Caen, Service de Génétique, Caen, France.
Lionel ArnaudDépartement de Génétique Médicale, APHP Sorbonne Université, Paris, France.
Dario R AlessiMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Esther SammlerMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.ORCID https://orcid.org/0000-0003-3218-7116

Funding

Carnegie Trust for the Universities of Scotland PHD010656Chief Scientist Office SCAF/18/01MRC PPU Reagents and Services MC_UU_00038/1
6 · The paper itself

Abstract

backgroundGain-of-kinase-function variants in LRRK2 are a leading cause of monogenic Parkinson's disease (PD).

objectivesWe tested the functional impact of a novel LRRK2 variant p.V1447L identified in a young-onset PD patient in vivo in peripheral blood, as well as in a robust cellular assay, alongside other variants in close proximity to V1447.

methodsWe measured LRRK2-dependent Rab10 phosphorylation in neutrophils and monocytes of a LRRK2 p.V1447L carrier with PD. We performed structural mapping and evaluated the potential impact of other LRRK2 variants at and around LRRK2 V1447.

resultsLRRK2 p.V1447L strongly increases LRRK2 kinase activity. We identified additional variants in the LRRK2 ROC:COR

conclusionsWe recommend reclassifying LRRK2 p.V1447L from variant of uncertain significance to likely pathogenic. Our study expands the range of putative loss-of-kinase function variants to LRRK2 missense variants. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2Parkinson DiseaseFemaleHumansMaleMiddle AgedPhosphorylationrab GTP-Binding ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanRab10 protein, humanrab GTP-Binding ProteinsgeneticsLRRK2Parkinson's diseaseperipheral blood neutrophilsRab10 phosphorylation

Identifiers

PMID40879463
PMCPMC12553989

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.