TBC1D1 Gene

Name	TBC1 (tre-2/USP6, BUB2, cdc16) domain family, member 1
Description	TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBC1D1 is a Rab GTPase–activating protein that plays a pivotal role in insulin‐stimulated GLUT4 trafficking. In adipocytes, ectopic expression of TBC1D1 impairs insulin‐mediated GLUT4 translocation, whereas loss of its catalytic (GAP) activity abolishes this effect. Genetic studies have identified a coding variant—most notably the Arg125Trp substitution—that segregates with severe obesity (especially in females and in familial settings), implicating TBC1D1 as an important player in metabolic regulation and energy balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn skeletal muscle, TBC1D1 is dynamically phosphorylated in response to contractile activity and metabolic stress. Acute exercise increases phosphorylation at multiple serine residues (including Ser237, Ser231, and Ser660) and concurrently enhances its binding to 14-3-3 proteins. These modifications are mediated by kinases such as AMPK and Akt, indicating that TBC1D1 acts as a key effector in the insulin-independent as well as exercise-stimulated glucose uptake pathways. Moreover, studies have demonstrated that differences in fiber type and even sex-specific factors modulate the extent and time course of TBC1D1 phosphorylation, underscoring its central role in muscle glucose homeostasis."}, {"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 role in muscle, TBC1D1 is expressed in pancreatic β‐cells where it is phosphorylated in response to glucose, suggesting a regulatory role in insulin secretion and β‐cell proliferation. In addition, emerging evidence from genetic association studies links TBC1D1 variants not only to obesity but also to phenotypes related to antipsychotic‐induced weight gain, indicating that alterations in its function may have broader metabolic and behavioral consequences."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent proteomic analyses have further revealed that the phosphotyrosine binding domains of TBC1D1 function as a scaffold for a network of proteins—such as VPS13A/C, EHBP1L1, MICAL1, and SERCA1—that may modulate GLUT4 vesicle dynamics. These interactions appear to selectively control the post-transcriptional levels and membrane targeting of GLUT4, reinforcing the notion that TBC1D1 is an essential integrative node in the regulation of cellular glucose uptake."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Steven Stone, Victor Abkevich, Deanna L Russell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl204"}], "href": "https://doi.org/10.1093/hmg/ddl204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16893906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16893906"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "William G Roach, Jose A Chavez, Cristinel P Mîinea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate specificity and effect on GLUT4 translocation of the Rab GTPase-activating protein Tbc1d1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20061798"}], "href": "https://doi.org/10.1042/BJ20061798"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17274760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17274760"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David Meyre, Morgane Farge, Cécile Lecoeur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn070"}], "href": "https://doi.org/10.1093/hmg/ddn070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18325908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18325908"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christian Frøsig, Christian Pehmøller, Jesper B Birk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2010.194811"}], "href": "https://doi.org/10.1113/jphysiol.2010.194811"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20837646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20837646"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Niels Jessen, Ding An, Aina S Lihn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exercise increases TBC1D1 phosphorylation in human skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00042.2011"}], "href": "https://doi.org/10.1152/ajpendo.00042.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21505148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21505148"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M H Vendelbo, A B Møller, J T Treebak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 min after a single bout of exercise."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.00044.2014"}], "href": "https://doi.org/10.1152/japplphysiol.00044.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24876356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24876356"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Krithika Lingappan, Weiwu Jiang, Lihua Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tox.2015.01.019"}], "href": "https://doi.org/10.1016/j.tox.2015.01.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25703676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25703676"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qiaoli Chen, Bingxian Xie, Sangsang Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Tbc1d1 "}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "Ser231Ala"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-016-4151-9"}], "href": "https://doi.org/10.1007/s00125-016-4151-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27826658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27826658"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anne Must, Sulev Kõks, Eero Vasar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variations in 4p locus are related to male completed suicide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuromolecular Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12017-008-8056-8"}], "href": "https://doi.org/10.1007/s12017-008-8056-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19115052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19115052"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Eva J Brandl, Arun K Tiwari, Tristram A Lett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Psychopharmacol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hup.2288"}], "href": "https://doi.org/10.1002/hup.2288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23364847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23364847"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sabine Rütti, Caroline Arous, Alexandra C Nica, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2013.10.050"}], "href": "https://doi.org/10.1016/j.febslet.2013.10.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24239544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24239544"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Irene S Tobias, Kara K Lazauskas, Jeremy Siu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex and fiber type independently influence AMPK, TBC1D1, and TBC1D4 at rest and during recovery from high-intensity exercise in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.00704.2019"}], "href": "https://doi.org/10.1152/japplphysiol.00704.2019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31895596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31895596"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sharon C Hook, Alexandra Chadt, Kate J Heesom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-74661-1"}], "href": "https://doi.org/10.1038/s41598-020-74661-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33087848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33087848"}]}]}]}
Synonyms	TBC1, TBC
Proteins	TBCD1_HUMAN
NCBI Gene ID	23216
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TBC1D1 has 7,156 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 127 datasets.

Click the + buttons to view associations for TBC1D1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 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 TBC1D1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TBC1D1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TBC1D1 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 TBC1D1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TBC1D1 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 TBC1D1 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 TBC1D1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TBC1D1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TBC1D1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TBC1D1 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 TBC1D1 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 TBC1D1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TBC1D1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TBC1D1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TBC1D1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TBC1D1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TBC1D1 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 TBC1D1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TBC1D1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TBC1D1 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 TBC1D1 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 TBC1D1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TBC1D1 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 TBC1D1 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 TBC1D1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TBC1D1 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 TBC1D1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TBC1D1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TBC1D1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TBC1D1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.