TBCK Gene

Name	TBC1 domain containing kinase
Description	This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBCK is emerging as a key regulator of cell growth and proliferation through its modulation of the mechanistic target of rapamycin (mTOR) signaling pathway. Studies have demonstrated that TBCK influences mTOR activity, as evidenced by decreased phosphorylation of downstream targets such as ribosomal protein S6 and by impaired transcription of mTOR complex components. In cellular models, loss‐of‐function mutations in TBCK result in reduced cell size, altered actin cytoskeleton organization, and diminished proliferative capacity—a constellation of effects that underscores its critical role in maintaining proper mTOR signaling dynamics. Furthermore, exogenous leucine can still stimulate mTOR activation in TBCK‐deficient cells, suggesting opportunities for targeted therapeutic intervention in conditions stemming from TBCK loss."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in mTOR regulation, TBCK harbors a TBC (Tre‐2/Bub2/Cdc16) domain that is characteristic of proteins with Rab GTPase–activating protein (Rab-GAP) activity. Structural analyses indicate that conserved residues within this domain are essential for its GAP function; indeed, deleterious mutations that truncate TBCK or disrupt key catalytic residues lead to impaired Rab-mediated vesicular trafficking. This disruption is thought to contribute to autophagosomal–lysosomal dysfunction observed in affected cells, as supported by studies showing accumulation of storage materials and altered apoptotic responses. Moreover, TBCK regulation by specific microRNAs, such as miR-1208, further emphasizes its involvement in cell survival pathways and reveals potential vulnerabilities that may be exploited in cancer therapy. TBCK’s modular structure is also highlighted by its participation in fusion events—such as the formation of a TBCK–P4HA2 hybrid protein in soft tissue tumors—underscoring its diverse functional repertoire."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its biochemical roles, TBCK function has profound clinical implications. Biallelic loss-of-function mutations in TBCK are consistently associated with severe neurodevelopmental disorders characterized by global developmental delay, hypotonia, intellectual disability, and progressive brain volume loss. In parallel, emerging reports have also noted that even heterozygous disruptions may subtly affect neurophysiology, manifesting as peripheral neuropathy or other mild neurogenic symptoms. These findings not only validate TBCK’s central role in neural development and maintenance but also suggest that its regulatory functions—encompassing both mTOR signaling and Rab-GAP activity—are critical for neuronal homeostasis. Advances in our understanding of TBCK have therefore laid a foundation for exploring novel therapeutic strategies, whether by modulating mTOR activity, correcting autophagic dysregulation, or targeting microRNA interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elizabeth J Bhoj, Dong Li, Margaret Harr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.03.016"}], "href": "https://doi.org/10.1016/j.ajhg.2016.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27040691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27040691"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yueli Liu, Xiaoyi Yan, Tianhua Zhou "}, {"type": "b", "children": [{"type": "t", "text": "TBCK influences cell proliferation, cell size and mTOR signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0071349"}], "href": "https://doi.org/10.1371/journal.pone.0071349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23977024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23977024"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jessica X Chong, Viviana Caputo, Ian G Phelps, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.01.016"}], "href": "https://doi.org/10.1016/j.ajhg.2016.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27040692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27040692"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xilma R Ortiz-González, Jesus A Tintos-Hernández, Kierstin Keller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.25130"}], "href": "https://doi.org/10.1002/ana.25130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29283439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29283439"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eugenio Zapata-Aldana, David Dongkyung Kim, Salma Remtulla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Further delineation of TBCK - Infantile hypotonia with psychomotor retardation and characteristic facies type 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2018.08.004"}], "href": "https://doi.org/10.1016/j.ejmg.2018.08.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30103036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30103036"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stefanie Beck-Wödl, Klaus Harzer, Marc Sturm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-018-0646-6"}], "href": "https://doi.org/10.1186/s40478-018-0646-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30591081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30591081"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Eun-Ae Kim, Ji-Hoon Jang, Eon-Gi Sung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms20143540"}], "href": "https://doi.org/10.3390/ijms20143540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31331056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31331056"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ioannis Panagopoulos, Ludmila Gorunova, Trond Viset, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2016.5096"}], "href": "https://doi.org/10.3892/or.2016.5096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27633981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27633981"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hanna Mandel, Morad Khayat, Elana Chervinsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBCK-related intellectual disability syndrome: Case study of two patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38019"}], "href": "https://doi.org/10.1002/ajmg.a.38019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27748029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27748029"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ningda Xu, Yi Cai, Jiarui Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An SNX31 variant underlies dominant familial exudative vitreoretinopathy-like pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.167032"}], "href": "https://doi.org/10.1172/jci.insight.167032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37053012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37053012"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Divya Nair, Abdias Diaz-Rosado, Elisa Varella-Branco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.63320"}], "href": "https://doi.org/10.1002/ajmg.a.63320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37353954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37353954"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Prem Chand, Asna Sulaiman, Salman Kirmani "}, {"type": "b", "children": [{"type": "t", "text": "Mutation Of TBC1 Domain Containing Kinase (TBCK) With Associated Intellectual Disability And Hypotonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pak Med Assoc (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.47391/JPMA.6733"}], "href": "https://doi.org/10.47391/JPMA.6733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37876076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37876076"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Saraswathy Sabanathan, Deepti Gulhane, Kshitij Mankad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuromuscul Disord (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nmd.2022.10.004"}], "href": "https://doi.org/10.1016/j.nmd.2022.10.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36522252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36522252"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Emily L Durham, Rajesh Angireddy, Aaron Black, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBCK syndrome: a rare multi-organ neurodegenerative disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Mol Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmed.2023.06.009"}], "href": "https://doi.org/10.1016/j.molmed.2023.06.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37455236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37455236"}]}]}]}
Synonyms	HSPC302, TBCKL, IHPRF3
Proteins	TBCK_HUMAN
NCBI Gene ID	93627
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TBCK has 4,812 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for TBCK from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TBCK Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TBCK gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of TBCK gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of TBCK gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TBCK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of TBCK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TBCK gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TBCK gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TBCK gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of TBCK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with TBCK gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TBCK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TBCK gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TBCK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TBCK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of TBCK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TBCK gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TBCK protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TBCK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing TBCK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TBCK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with TBCK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of TBCK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TBCK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TBCK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TBCK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TBCK protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TBCK gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with TBCK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TBCK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TBCK gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with TBCK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TBCK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TBCK gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TBCK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TBCK gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing TBCK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TBCK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TBCK gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing TBCK from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TBCK gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.