TBL2 Gene

HGNC Family	WD repeat domain containing (WDR)
Name	transducin (beta)-like 2
Description	This gene encodes a member of the beta-transducin protein family. Most proteins of the beta-transducin family are involved in regulatory functions. This protein is possibly involved in some intracellular signaling pathway. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genome‐wide association studies have implicated TBL2 in the regulation of plasma lipid levels. Genetic variants in the TBL2 locus have been associated with triglyceride concentrations and severe forms of hypertriglyceridemia, suggesting that common alleles at this locus contribute to the polygenic regulation of lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its genetic association with lipid traits, TBL2 has an important cellular role in the endoplasmic reticulum (ER) stress response. As an ER‐localized type I transmembrane protein with a C-terminal WD40 domain, it binds preferentially to the phosphorylated form of the ER stress sensor PERK, thereby playing a key role in modulating stress signaling. Notably, TBL2 interacts with the 60S ribosomal subunit and directly associates with ATF4 mRNA through its WD40 domain to regulate ATF4 translation under conditions of ER stress or nutrient deprivation. Such activities help maintain proper adaptive responses and cell survival under adverse conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, TBL2 appears to participate in pathways relevant to oxidative/nitrosative stress and tumor suppression. It forms a high-affinity complex with the prenyltransferase TERE1, a protein implicated in vitamin K-2 and coenzyme Q10 biosynthesis, thereby linking TBL2 to mitochondrial function, lipid metabolism, and nuclear receptor signaling. Consistent with these interactions, alterations in TBL2 expression and localization have been associated with cancer progression, and its identification as a candidate driver gene in lung adenocarcinoma underscores the potential clinical significance of its ER stress–related and metabolic functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sekar Kathiresan, Olle Melander, Candace Guiducci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.75"}], "href": "https://doi.org/10.1038/ng.75"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18193044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18193044"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jian Wang, Matthew R Ban, Guang Yong Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polygenic determinants of severe hypertriglyceridemia."}]}, {"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/ddn188"}], "href": "https://doi.org/10.1093/hmg/ddn188"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18596051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18596051"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Robert A Hegele, Matthew R Ban, Neil Hsueh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp361"}], "href": "https://doi.org/10.1093/hmg/ddp361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19656773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19656773"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yang Li, Shuai Liu, Yong-Tao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids Health Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12944-020-01359-8"}], "href": "https://doi.org/10.1186/s12944-020-01359-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32811528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32811528"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yoshinori Tsukumo, Satomi Tsukahara, Aki Furuno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBL2 is a novel PERK-binding protein that modulates stress-signaling and cell survival during endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0112761"}], "href": "https://doi.org/10.1371/journal.pone.0112761"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25393282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25393282"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yoshinori Tsukumo, Satomi Tsukahara, Aki Furuno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The endoplasmic reticulum-localized protein TBL2 interacts with the 60S ribosomal subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.04.144"}], "href": "https://doi.org/10.1016/j.bbrc.2015.04.144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25976671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25976671"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yoshinori Tsukumo, Satomi Tsukahara, Aki Furuno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBL2 Associates With ATF4 mRNA Via Its WD40 Domain and Regulates Its Translation During ER Stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.25301"}], "href": "https://doi.org/10.1002/jcb.25301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26239904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26239904"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "William J Fredericks, Terry McGarvey, Huiyi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TERE1 protein interacts with mitochondrial TBL2: regulation of trans-membrane potential, ROS/RNS and SXR target genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.24567"}], "href": "https://doi.org/10.1002/jcb.24567"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23564352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23564352"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Keisuke Kosai, Takaaki Masuda, Akihiro Kitagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transducin Beta-Like 2 is a Potential Driver Gene that Adapts to Endoplasmic Reticulum Stress to Promote Tumor Growth of Lung Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-023-13864-y"}], "href": "https://doi.org/10.1245/s10434-023-13864-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37477745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37477745"}]}]}]}
Synonyms	WS-BETATRP, WBSCR13
Proteins	TBL2_HUMAN
NCBI Gene ID	26608
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TBL2 has 6,712 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 114 datasets.

Click the + buttons to view associations for TBL2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TBL2 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 TBL2 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TBL2 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 TBL2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TBL2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TBL2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TBL2 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 TBL2 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 TBL2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TBL2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TBL2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TBL2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TBL2 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 TBL2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TBL2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with TBL2 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 TBL2 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 TBL2 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 TBL2 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 TBL2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TBL2 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 TBL2 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 TBL2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TBL2 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 TBL2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TBL2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TBL2 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 TBL2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.