{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Flores-Mendez M"],"funding":["NINDS NIH HHS"],"pubmed_abstract":["Monogenic pediatric neurodegenerative disorders can reveal fundamental cellular mechanisms that underlie selective neuronal vulnerability. TBCK-Encephaloneuronopathy (TBCKE) is a rare autosomal recessive disorder caused by stop-gain variants in the <i>TBCK</i> gene. Clinically, patients show evidence of profound neurodevelopmental delays, but also symptoms of progressive encephalopathy and motor neuron disease. Yet, the physiological role of TBCK protein remains unclear. We report a human neuronal TBCKE model, derived from iPSCs homozygous for the Boricua variant (p.R126X). Using unbiased proteomic analyses of human neurons, we find TBCK interacts with PPP1R21, C12orf4, and Cryzl1, consistent with TBCK being part of the FERRY mRNA transport complex. Loss of TBCK leads to depletion of C12OR"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.03.02.641041"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11908138"],"repository":["biostudies-literature"],"pubmed_title":["TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in patient-derived neurons."],"pmcid":["PMC11908138"],"funding_grant_id":["K02 NS112456","R01 NS126541","R01 NS132795"],"pubmed_authors":["Ortiz-Gonzalez XR","Lo TY","Miles L","Ramos-Rodriguez L","Flores-Mendez M","Tintos-Hernandez JA","Song Y"],"additional_accession":[]},"is_claimable":false,"name":"TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in patient-derived neurons.","description":"Monogenic pediatric neurodegenerative disorders can reveal fundamental cellular mechanisms that underlie selective neuronal vulnerability. TBCK-Encephaloneuronopathy (TBCKE) is a rare autosomal recessive disorder caused by stop-gain variants in the <i>TBCK</i> gene. Clinically, patients show evidence of profound neurodevelopmental delays, but also symptoms of progressive encephalopathy and motor neuron disease. Yet, the physiological role of TBCK protein remains unclear. We report a human neuronal TBCKE model, derived from iPSCs homozygous for the Boricua variant (p.R126X). Using unbiased proteomic analyses of human neurons, we find TBCK interacts with PPP1R21, C12orf4, and Cryzl1, consistent with TBCK being part of the FERRY mRNA transport complex. Loss of TBCK leads to depletion of C12OR","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-04-08T18:38:17.023Z","creation":"2025-04-05T12:37:02.569Z"},"accession":"S-EPMC11908138","cross_references":{"pubmed":["40093117"],"doi":["10.1101/2025.03.02.641041"]}}