TBC1D15 Gene

Name	TBC1 domain family, member 15
Description	This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBC1D15 is emerging as a key regulator of mitochondrial quality control and dynamics. In damaged mitochondria, TBC1D15 localizes to the organelle through its binding to the outer–mitochondrial membrane receptor Fis1 and interfaces with the nascent autophagosomal membrane via LC3/GABARAP interactions, thus constraining autophagosome formation to the damaged cargo (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, independent analyses have revealed that TBC1D15 modulates mitochondrial morphology by functioning at sites distinct from the canonical fission machinery.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its mitochondrial roles, TBC1D15 functions as a Rab GTPase-activating protein that is highly selective for Rab7. By stimulating Rab7 GTP hydrolysis, it regulates late endosomal–lysosomal dynamics, affecting lysosomal morphology and promoting proper trafficking. This activity is critical not only for endosomal maturation and cholesterol export—as seen in Niemann–Pick type C1 models and GLUT4 translocation in skeletal muscle—but also for cellular responses to interferon‐β that control autophagy via microRNA-mediated modulation of TBC1D15 levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in vesicular trafficking, TBC1D15 has been implicated in the regulation of cell division and oncogenic signaling. Its depletion leads to aberrant activation of RhoA, triggering enhanced membrane blebbing and disruptions in cytokinesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In tumor‐initiating stem‐like cells, overexpression of TBC1D15 promotes oncogenesis by destabilizing p53 and modulating NOTCH1 signaling through interactions with NUMB, thereby facilitating self‐renewal and supporting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kenta Onoue, Akihiro Jofuku, Reiko Ban-Ishihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.111211"}], "href": "https://doi.org/10.1242/jcs.111211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23077178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23077178"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Koji Yamano, Adam I Fogel, Chunxin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.01612"}], "href": "https://doi.org/10.7554/eLife.01612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24569479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24569479"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ugochukwu K Ihenacho, Rafael Toro, Rana H Mansour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A conserved, noncanonical insert in FIS1 mediates TBC1D15 and DRP1 recruitment for mitochondrial fission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.105303"}], "href": "https://doi.org/10.1016/j.jbc.2023.105303"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37777154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37777154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiang-Ming Zhang, Bong Walsh, Christina A Mitchell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.07.070"}], "href": "https://doi.org/10.1016/j.bbrc.2005.07.070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16055087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16055087"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eigen R Peralta, Brent C Martin, Aimee L Edinger "}, {"type": "b", "children": [{"type": "t", "text": "Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.111633"}], "href": "https://doi.org/10.1074/jbc.M110.111633"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20363736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20363736"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jia Wu, Dandan Cheng, Li Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D15 affects glucose uptake by regulating GLUT4 translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2018.10.025"}], "href": "https://doi.org/10.1016/j.gene.2018.10.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30316925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30316925"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Elsa Meneses-Salas, Ana García-Melero, Kristiina Kanerva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-019-03330-y"}], "href": "https://doi.org/10.1007/s00018-019-03330-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31664461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31664461"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Patrick Ejlerskov, David C Rubinsztein, Roger Pocock "}, {"type": "b", "children": [{"type": "t", "text": "IFNB/interferon-β regulates autophagy via a "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MIR1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-TBC1D15-RAB7 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2020.1718384"}], "href": "https://doi.org/10.1080/15548627.2020.1718384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31958036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31958036"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yuko Takahara, Masao Maeda, Hitoki Hasegawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of TBC1D15 promotes RhoA activation and membrane blebbing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-013-1921-2"}], "href": "https://doi.org/10.1007/s11010-013-1921-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24337944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24337944"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hye Yeon Choi, Hifzur R Siddique, Mengmei Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p53 destabilizing protein skews asymmetric division and enhances NOTCH activation to direct self-renewal of TICs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-16616-8"}], "href": "https://doi.org/10.1038/s41467-020-16616-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32555153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32555153"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hye Yeon Choi, Yicheng Zhu, Xuyao Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s12276-024-01174-6"}], "href": "https://doi.org/10.1038/s12276-024-01174-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38409448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38409448"}]}]}]}
Synonyms	RAB7-GAP
Proteins	TBC15_HUMAN
NCBI Gene ID	64786
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TBC1D15 has 7,335 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 112 datasets.

Click the + buttons to view associations for TBC1D15 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TBC1D15 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 TBC1D15 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 TBC1D15 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 TBC1D15 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 TBC1D15 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 TBC1D15 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 TBC1D15 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of TBC1D15 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TBC1D15 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TBC1D15 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 TBC1D15 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 TBC1D15 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TBC1D15 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TBC1D15 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 TBC1D15 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TBC1D15 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 TBC1D15 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing TBC1D15 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TBC1D15 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TBC1D15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TBC1D15 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing TBC1D15 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 TBC1D15 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 TBC1D15 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 TBC1D15 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TBC1D15 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TBC1D15 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TBC1D15 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TBC1D15 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TBC1D15 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TBC1D15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TBC1D15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TBC1D15 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 TBC1D15 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TBC1D15 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 TBC1D15 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TBC1D15 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TBC1D15 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TBC1D15 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 TBC1D15 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TBC1D15 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.