Evidence map›Paper›PMID 40100287›Full record

ArticleCerebellum (London, England)2025

Novel C1A Domain Variant in Protein Kinase Cγ in Spinocerebellar Ataxia Type 14 Decreases Autoinhibition.

Gayatri Raj Ghosh, Tiffany H Kao, Connolly G Steigerwald, Nora L Chan, Alexandra C Newton, Nicolas J Abreu

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Cerebellum (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Gayatri Raj Ghosh *Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Tiffany H Kao *Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Connolly G SteigerwaldDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Nora L ChanDepartment of Neurology, NYU Grossman Long Island School of Medicine, Mineola, NY, USA.
Alexandra C NewtonDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Nicolas J AbreuDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, USA. nicolas.abreu@nyulangone.org.

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
Molecular Mechanisms of Cell SignalingR35GM122523 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALEXANDRA C. NEWTON · 2017 to 2026
$6.7M
Structural and Molecular Mechanisms for Dysregulation of Protein Kinase C Gamma in Cerebellar AtaxiaR01NS120725 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALEXANDRA C. NEWTON, SUSAN S. TAYLOR · 2021 to 2026
$3.9M
NIGMS NIH HHS R35 GM122523NIGMS NIH HHS T32 GM007752NIH HHS T32 GM007752NINDS NIH HHS R01 NS120725
6 · The paper itself

Abstract

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by adult-onset cerebellar ataxia, and occasionally pyramidal signs, cognitive changes, sensory changes, myoclonus, and tremor. SCA14 results from heterozygous gain-of-function pathogenic variants in PRKCG, which encodes protein kinase Cγ. The aim was to elucidate the molecular mechanism of disease in a 60-year-old man with SCA14 due to a novel heterozygous variant in PRKCG c.154T > C p.(C52R). Next-generation sequencing was completed in the proband, targeted variant analysis was conducted in his family, and biochemical functional assays were performed. The C52R variant segregated with disease. Like other C1A domain variants, it had increased basal activity yet was unresponsive to agonist stimulation and was relatively resistant to down-regulation. This expands the genetic landscape of SCA14 and supports the condition as a gain-of-function disease, with variants in the C1A domain having leaky activity yet unresponsiveness to agonist stimulation.

Indexed as

Protein Kinase CSpinocerebellar AtaxiasHumansMaleMiddle AgedMutationPedigreeProtein DomainsProtein Kinase Cprotein kinase C gammaMedical geneticsMolecular biologyProtein kinase C-gammaSpinocerebellar ataxias

Identifiers

PMID40100287
PMCPMC11991623

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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.