TMBIM6 Gene

Name	transmembrane BAX inhibitor motif containing 6
Description	Enables endoribonuclease inhibitor activity and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of intrinsic apoptotic signaling pathway; negative regulation of macromolecule metabolic process; and response to L-glutamate. Acts upstream of or within negative regulation of calcium ion transport into cytosol. Located in endoplasmic reticulum membrane. Biomarker of cervical squamous cell carcinoma and prostate carcinoma. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMBIM6, also known as Bax inhibitor‐1 (BI‐1), is an evolutionarily conserved multi‐transmembrane protein primarily localized in the endoplasmic reticulum that functions as a pH‐sensitive Ca²⁺ leak channel. By mediating ER Ca²⁺ efflux, it modulates intracellular Ca²⁺ homeostasis and mitigates ER stress, thereby protecting cells from stress‐induced apoptosis and maintaining cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in the ER, TMBIM6 also orchestrates Ca²⁺ signaling between organelles. Its leakage of Ca²⁺ from the ER not only contributes to the regulation of basal intracellular Ca²⁺ but also increases the resting Ca²⁺ level in lysosomes. This localized Ca²⁺ release—mediated through channels such as MCOLN1/TRPML1—triggers downstream pathways including calcineurin activation and TFEB nuclear translocation, which in turn enhance autophagy and mitochondrial quality control. In cardiomyocytes subjected to hypoxic and oxidative stress, modulation of TMBIM6 expression has been shown to regulate these protective autophagic responses, thereby improving cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of TMBIM6 has been implicated in a variety of pathological conditions. In cancer, for example, upregulation of TMBIM6 promotes tumor progression by enhancing mTORC2 signaling, stimulating glycolysis, protein synthesis, and lipid metabolism. Moreover, non‐coding RNAs have been identified that modulate TMBIM6 expression in breast cancer and glioblastoma, affecting cell viability, migration, and apoptotic responses via alterations in ERK signaling. In age‐related liver disease, decreased TMBIM6 expression correlates with aberrant unfolded protein response activation, redox‐mediated modifications of key ER stress sensors, and increased lipid accumulation. Dysregulated TMBIM6 function may also contribute to disturbances in ER and lipid homeostasis during viral infections such as SARS‑CoV‑2, highlighting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dmitrij A Lisak, Teresa Schacht, Vitalij Enders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER CA²⁺-filling state."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2015.03.002"}], "href": "https://doi.org/10.1016/j.bbamcr.2015.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25764978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25764978"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hyun-Kyoung Kim, Geum-Hwa Lee, Kashi Raj Bhattarai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMBIM6 (transmembrane BAX inhibitor motif containing 6) enhances autophagy through regulation of lysosomal calcium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2020.1732161"}], "href": "https://doi.org/10.1080/15548627.2020.1732161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32167007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32167007"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xing Chang, Tian Zhang, Qingyan Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1/TMBIM6-Related Mitophagy and Endoplasmic Reticulum Stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oxid Med Cell Longev (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/5529913"}], "href": "https://doi.org/10.1155/2021/5529913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33859776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33859776"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hyun-Kyoung Kim, Kashi Raj Bhattarai, Raghu Patil Junjappa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-17802-4"}], "href": "https://doi.org/10.1038/s41467-020-17802-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32782388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32782388"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yanru Liao, Zhenxiong Qiu, Ling Bai "}, {"type": "b", "children": [{"type": "t", "text": "miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2021.12493"}], "href": "https://doi.org/10.3892/mmr.2021.12493"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34651659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34651659"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kashi Raj Bhattarai, Hyun-Kyoung Kim, Manoj Chaudhary, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMBIM6 regulates redox-associated posttranslational modifications of IRE1α and ER stress response failure in aging mice and humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2021.102128"}], "href": "https://doi.org/10.1016/j.redox.2021.102128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34562874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34562874"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qizheng Han, Junhao Wang, Haihua Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMBIM6, a potential virus target protein identified by integrated multiomics data analysis in SARS-CoV-2-infected host cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202718"}], "href": "https://doi.org/10.18632/aging.202718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33744846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33744846"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Z Jin, L-H Piao, G-C Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) promotes glioblastoma multiforme progression via regulating miR-1301-3p/TMBIM6 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202011_23810"}], "href": "https://doi.org/10.26355/eurrev_202011_23810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33275233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33275233"}]}]}]}
Synonyms	TEGT, BAXI1, BI-1
Proteins	BI1_HUMAN
NCBI Gene ID	7009
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TMBIM6 has 8,508 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 106 datasets.

Click the + buttons to view associations for TMBIM6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TMBIM6 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 TMBIM6 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 TMBIM6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TMBIM6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TMBIM6 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 TMBIM6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TMBIM6 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 TMBIM6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TMBIM6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TMBIM6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TMBIM6 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 TMBIM6 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 TMBIM6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TMBIM6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TMBIM6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 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 TMBIM6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TMBIM6 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 TMBIM6 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 TMBIM6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TMBIM6 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 TMBIM6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TMBIM6 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 TMBIM6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TMBIM6 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 TMBIM6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of TMBIM6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of TMBIM6 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.