TBC1D16 Gene

Name	TBC1 domain family, member 16
Description	Enables GTPase activator activity. Involved in regulation of receptor recycling. Located in cytosol and early endosome. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBC1D16, a Rab GTPase‐activating protein, has emerged as an important regulator of intracellular protein trafficking in melanoma. Multiple studies have shown that TBC1D16 contributes to tumor growth by modulating the recycling and degradation of key receptors. In one study, integrative genomic analyses identified TBC1D16 as a candidate dependency in melanoma, implicating aberrant regulation of protein trafficking in tumor proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Further investigation revealed that an epigenetically reactivated, short isoform—TBC1D16-47KD—exacerbates melanoma growth and metastasis by targeting Rab GTPases such as Rab5C to control epidermal growth factor receptor (EGFR) signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, mechanistic studies have demonstrated that TBC1D16 acts as a GTPase‐activating protein for Rab4A, altering receptor recycling dynamics and enhancing EGFR degradation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and methylation changes at the TBC1D16 locus are characteristic of metastasis in melanoma and other tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic role in melanoma, TBC1D16 has been implicated in antiviral defense. One study identified TBC1D16 as a novel antiviral factor during prototype foamy virus (PFV) infection. TBC1D16, which is significantly down-regulated upon PFV infection, targets Rab5C to suppress viral replication and promotes IFN-β production, underscoring its role in host antiviral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTBC1D16’s functional significance extends to other cancer types as well. In epithelial ovarian cancer, higher expression of TBC1D16 correlates with advanced local disease yet is paradoxically associated with favorable overall survival and lower levels of VEGF."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of acute myeloid leukemia, elevated TBC1D16 expression and specific DNA methylation patterns are linked to increased risk of non-response to chemotherapy and poorer overall survival, while experimental knockdown of TBC1D16 in AML cells reduces proliferation and affects ERK signaling, highlighting its potential as a prognostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Uri David Akavia, Oren Litvin, Jessica Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An integrated approach to uncover drivers of cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2010.11.013"}], "href": "https://doi.org/10.1016/j.cell.2010.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129771"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miguel Vizoso, Humberto J Ferreira, Paula Lopez-Serra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3863"}], "href": "https://doi.org/10.1038/nm.3863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26030178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26030178"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Basem S Goueli, Marianne Broome Powell, Elizabeth C Finger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1204540109"}], "href": "https://doi.org/10.1073/pnas.1204540109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23019362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23019362"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Euan J Rodger, Aniruddha Chatterjee, Peter A Stockwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterisation of DNA methylation changes in EBF3 and TBC1D16 associated with tumour progression and metastasis in multiple cancer types."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Epigenetics (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13148-019-0710-5"}], "href": "https://doi.org/10.1186/s13148-019-0710-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31383000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31383000"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jun Yan, Yingcheng Zheng, Peipei Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Host Protein TBC1D16, a GTPase Activating Protein of Rab5C, Inhibits Prototype Foamy Virus Replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2021.658660"}], "href": "https://doi.org/10.3389/fimmu.2021.658660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34367131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34367131"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zunxian Yang, Hongwei Shen, Weipeng He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of TBC1D16 Is Associated with Favorable Prognosis of Epithelial Ovarian Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tohoku J Exp Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1620/tjem.245.141"}], "href": "https://doi.org/10.1620/tjem.245.141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29962380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29962380"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Han Liu, Peng Chen, Yong-Long Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2021.173894"}], "href": "https://doi.org/10.1016/j.ejphar.2021.173894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33476656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33476656"}]}]}]}
Proteins	TBC16_HUMAN
NCBI Gene ID	125058
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TBC1D16 has 6,680 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 107 datasets.

Click the + buttons to view associations for TBC1D16 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TBC1D16 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TBC1D16 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 TBC1D16 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TBC1D16 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 TBC1D16 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TBC1D16 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 TBC1D16 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TBC1D16 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TBC1D16 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TBC1D16 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 TBC1D16 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 2025	cellular components co-occuring with TBC1D16 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 TBC1D16 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TBC1D16 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TBC1D16 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TBC1D16 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 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 TBC1D16 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TBC1D16 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 TBC1D16 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 TBC1D16 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TBC1D16 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 TBC1D16 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TBC1D16 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 TBC1D16 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TBC1D16 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 TBC1D16 from the GeneSigDB Published Gene Signatures dataset.