ArticleClinical genetics2021
PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy.
Article in Clinical genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 14 papers.
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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.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Epileptic-Dyskinetic Encephalopathy Associated with a PPP3CA Variant: Expansion of the Phenotypic Spectrum.Movement disorders clinical practice · 2026Article
- Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence.Biomolecules · 2026Article
- The clinical missense variant E282K in PPP3CA/calcineurin shifts substrate dephosphorylation by altering active site recruitment.Nature communications · 2026Article
- Remote spatial memory deficits in mouse models of neuropsychiatric disorders with immature dentate gyrus phenotype.The international journal of neuropsychopharmacology · 2025Article
- New variants and genotype-phenotype correlation ofFrontiers in neuroscience · 2025Article
- Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology.PloS one · 2025Article
- Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter.Orphanet journal of rare diseases · 2024Article
- Identification and validation of genes associated with prognosis of cisplatin-resistant ovarian cancer.BMC cancer · 2024Article
- Astroglial calcium signaling and homeostasis in tuberous sclerosis complex.Acta neuropathologica · 2024Article
- Vascular endothelial growth factor B regulates insulin secretion in β cells of type 2 diabetes mellitus mice via PLCγ and the IP3R‑evoked Ca2Molecular medicine reports · 2023Article
- Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice.Molecular brain · 2022Article
- Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort.Molecular cytogenetics · 2022Article
- Investigation of Copy Number Variations (CNVs) of the GoatAnimals : an open access journal from MDPI · 2022Article
- Case report: A novelFrontiers in neurology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
PPP3CA encodes the catalytic subunit of calcineurin, a calcium-calmodulin-regulated serine-threonine phosphatase. Loss-of-function (LoF) variants in the catalytic domain have been associated with epilepsy, while gain-of-function (GoF) variants in the auto-inhibitory domain cause multiple congenital abnormalities. We herein report five new patients with de novo PPP3CA variants. Interestingly, the two frameshift variants in this study and the six truncating variants reported previously are all located within a 26-amino acid region in the regulatory domain (RD). Patients with a truncating variant had more severe earlier onset seizures compared to patients with a LoF missense variant, while autism spectrum disorder was a more frequent feature in the latter. Expression studies of a truncating variant showed apparent RNA expression from the mutant allele, but no detectable mutant protein. Our data suggest that PPP3CA truncating variants clustered in the RD, causing more severe early-onset refractory epilepsy and representing a type of variants distinct from LoF or GoF missense variants.
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Registered trials
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