ArticleAmerican journal of human genetics2016
Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Mapping the Diverse Genetic Disorders and Rare Diseases Among the Syrian Population: Implications on Refugee Health and Health Services in Host Countries.Journal of immigrant and minority health · 2020Pooled it
- Human TBC1 domain-containing kinase is a class I multidomain pseudokinase.Protein expression and purification · 2027Article
- A novel mouse model of rare neurodevelopmental disorder, TBCK Syndrome.bioRxiv : the preprint server for biology · 2026Article
- TBCK Deficiency Alters Ribosomal Function, RNA Splicing, and miRNA Networks: Insights from Multi-Omics Analyses.bioRxiv : the preprint server for biology · 2025Article
- Neurogenetic disorders associated with mutations in the FERRY complex: a novel disease class?Biology open · 2025Review
- A Novel Human TBCK- Neuronal Cell Model Results in Severe Neurodegeneration and Partial Rescue with Mitochondrial Fission Inhibition.bioRxiv : the preprint server for biology · 2024Article
- Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.American journal of medical genetics. Part A · 2023Article
- TBCK syndrome: a rare multi-organ neurodegenerative disease.Trends in molecular medicine · 2023Article
- A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.Human mutation · 2022Article
- Identification of a novel pathogenic TBCK variant in a Chinese patient with infantile hypotonia with psychomotor retardation and characteristic facies type 3 (IHPRF3): a case report.BMC pediatrics · 2022Article
- Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.Journal of human genetics · 2021Article
- 5q35 duplication presents with psychiatric and undergrowth phenotypes mediated by NSD1 overexpression and mTOR signaling downregulation.Human genetics · 2021Article
- Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport.Frontiers in cellular neuroscience · 2021Article
- Multiple functions of TBCK protein in neurodevelopment disorders and tumors.Oncology letters · 2021Review
- Mitochondrial Dysfunction: A Common Denominator in Neurodevelopmental Disorders?Developmental neuroscience · 2021Review
- Lysosomal dysfunction impairs mitochondrial quality control and is associated with neurodegeneration inBrain communications · 2021Article
- Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK.Muscle & nerve · 2020Article
- Expanding the clinical and phenotypic heterogeneity associated with biallelic variants in ACO2.Annals of clinical and translational neurology · 2020Article
- Emerging Role of the Autophagy/Lysosomal Degradative Pathway in Neurodevelopmental Disorders With Epilepsy.Frontiers in cellular neuroscience · 2020Article
- A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype.Molecular genetics & genomic medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 11 institutions in 5 countries.
Funding
Abstract
Through an international multi-center collaboration, 13 individuals from nine unrelated families and affected by likely pathogenic biallelic variants in TBC1-domain-containing kinase (TBCK) were identified through whole-exome sequencing. All affected individuals were found to share a core phenotype of intellectual disability and hypotonia, and many had seizures and showed brain atrophy and white-matter changes on neuroimaging. Minor non-specific facial dysmorphism was also noted in some individuals, including multiple older children who developed coarse features similar to those of storage disorders. TBCK has been shown to regulate the mammalian target of rapamycin (mTOR) signaling pathway, which is also stimulated by exogenous leucine supplementation. TBCK was absent in cells from affected individuals, and decreased phosphorylation of phospho-ribosomal protein S6 was also observed, a finding suggestive of downregulation of mTOR signaling. Lastly, we demonstrated that activation of the mTOR pathway in response to L-leucine supplementation was retained, suggesting a possible avenue for directed therapies for this condition.
Indexed as
Identifiers
What OpenQuestion holds
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.