ArticleAmerican journal of human genetics2020
De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy.
Article in American journal of human genetics, 2020. 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 29 papers.
What it found
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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
29 citing papers in PubMed, 43 citations in OpenAlex.
- Uncovering phenotypic expansion in AXIN2-related disorders through precision animal modeling.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Uncovering functional insights into human pathogenic variants in CDK19 using Drosophila models.Human molecular genetics · 2026Article
- Case Series of Nizon-Isidor Syndrome by Heterozygous Variants in MED12L With Further Evidence of Mitotic Instability in One Case With Diploid-Triploid Mosaicism.American journal of medical genetics. Part A · 2026Article
- Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.Genes · 2025Review
- Drosophila melanogaster as a rapid in vivo assay system for preclinical anti-seizure medication testing.Epilepsia open · 2025Article
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Review
- Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.Nature communications · 2024Article
- Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans.Nature reviews. Genetics · 2024Review
- Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.Brain : a journal of neurology · 2023Article
- Discovery of small molecule degraders for modulating cell cycle.Frontiers of medicine · 2023Review
- A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins.Cell reports · 2023Article
- Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in theFrontiers in molecular neuroscience · 2023Article
- De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in Drosophila.Human molecular genetics · 2022Article
- Interstitial deletions in the proximal regions of 6q: 12 original cases and a literature review.Intractable & rare diseases research · 2022Article
- The Mediator kinase module: an interface between cell signaling and transcription.Trends in biochemical sciences · 2022Review
- Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases.Experimental neurobiology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
We identified three unrelated individuals with de novo missense variants in CDK19, encoding a cyclin-dependent kinase protein family member that predominantly regulates gene transcription. These individuals presented with hypotonia, global developmental delay, epileptic encephalopathy, and dysmorphic features. CDK19 is conserved between vertebrate and invertebrate model organisms, but currently abnormalities in CDK19 are not known to be associated with a human disorder. Loss of Cdk8, the fly homolog of CDK19, causes larval lethality, which is suppressed by expression of human CDK19 reference cDNA. In contrast, the CDK19 p.Tyr32His and p.Thr196Ala variants identified in the affected individuals fail to rescue the loss of Cdk8 and behave as null alleles. Additionally, neuronal RNAi-mediated knockdown of Cdk8 in flies results in semi-lethality. The few eclosing flies exhibit severe seizures and a reduced lifespan. Both phenotypes are fully suppressed by moderate expression of the CDK19 reference cDNA but not by expression of the two variants. Finally, loss of Cdk8 causes an obvious loss of boutons and synapses at larval neuromuscular junctions (NMJs). Together, our findings demonstrate that human CDK19 fully replaces the function of Cdk8 in the fly, the human disease-associated CDK19 variants behave as strong loss-of-function variants, and deleterious CDK19 variants underlie a syndromic neurodevelopmental disorder.
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Registered trials
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.