BNIP3 Gene

Name	BCL2/adenovirus E1B 19kDa interacting protein 3
Description	This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation. [provided by RefSeq, Dec 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BNIP3 is an atypical BH3‐only Bcl-2 family member that plays a pivotal role in cellular adaptation to metabolic and hypoxic stress. Its expression is robustly induced by stress‐responsive transcription factors such as FoxO3 and hypoxia‐inducible factor 1 (HIF-1), which in turn trigger BNIP3‐dependent autophagy in tissues including skeletal muscle and the myocardium."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " As an autophagy receptor, BNIP3 mediates the selective clearance of damaged mitochondria (mitophagy) and endoplasmic reticulum (ER-phagy) through its LC3-interacting region; this process is critically dependent on its ability to homodimerize and on post-translational modifications—such as phosphorylation near its LIR—that modulate its binding affinity for Atg8 proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In certain contexts, BNIP3-driven autophagy serves a protective function by eliminating dysfunctional organelles, reducing reactive oxygen species accumulation, and thereby restraining pro-apoptotic signals. However, excessive or sustained BNIP3 activation may also promote cell death, as observed in models of hypoxia-induced autophagic cell death and in myocardial pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In renal cell carcinoma, BNIP3 exhibits a complex behavior where its expression is positively regulated by HIF-1α yet counteracted by HIF-2α, highlighting its context-dependent contribution to cell fate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in breast cancer, epigenetic mechanisms—specifically, FTO-mediated m6A demethylation of BNIP3 mRNA—lead to reduced BNIP3 levels, thereby diminishing its tumor-suppressive influence by impairing mitochondrial quality control and enhancing oncogenic metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In a related tumor model, loss of BNIP3 function was shown to delay the clearance of damaged mitochondria, resulting in excessive reactive oxygen species generation and the activation of pro-tumorigenic pathways, thereby underscoring its suppressive role in cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, BNIP3 integrates hypoxic and metabolic signals to modulate autophagy and mitochondrial turnover, functioning as a molecular switch between cytoprotection and cell death. Its dual role—in promoting survival by facilitating the removal of damaged organelles and in triggering apoptosis under extreme stress—renders BNIP3 an attractive therapeutic target in conditions such as muscle wasting, ischemic heart disease, and cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Cristina Mammucari, Giulia Milan, Vanina Romanello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FoxO3 controls autophagy in skeletal muscle in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2007.11.001"}], "href": "https://doi.org/10.1016/j.cmet.2007.11.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18054315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18054315"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Grégory Bellot, Raquel Garcia-Medina, Pierre Gounon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00166-09"}], "href": "https://doi.org/10.1128/MCB.00166-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19273585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19273585"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rita A Hanna, Melissa N Quinsay, Amabel M Orogo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.322933"}], "href": "https://doi.org/10.1074/jbc.M111.322933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22505714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22505714"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanyan Zhu, Stefan Massen, Marco Terenzio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.399345"}], "href": "https://doi.org/10.1074/jbc.M112.399345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23209295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23209295"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meghan B Azad, Yongqiang Chen, Elizabeth S Henson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.5278"}], "href": "https://doi.org/10.4161/auto.5278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18059169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18059169"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jee-Youn Kim, Hyun-Jong Ahn, Jong-Hoon Ryu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20030613"}], "href": "https://doi.org/10.1084/jem.20030613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14699081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14699081"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Raju R Raval, Kah Weng Lau, Maxine G B Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.13.5675-5686.2005"}], "href": "https://doi.org/10.1128/MCB.25.13.5675-5686.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15964822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15964822"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yi Niu, Ziyou Lin, Arabella Wan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-019-1004-4"}], "href": "https://doi.org/10.1186/s12943-019-1004-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30922314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30922314"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aparajita H Chourasia, Kristin Tracy, Casey Frankenberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201540759"}], "href": "https://doi.org/10.15252/embr.201540759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26232272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26232272"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Youngil Lee, Hwa-Youn Lee, Rita A Hanna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00368.2011"}], "href": "https://doi.org/10.1152/ajpheart.00368.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21890690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21890690"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kristin Tracy, Benjamin C Dibling, Benjamin T Spike, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02246-06"}], "href": "https://doi.org/10.1128/MCB.02246-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17576813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17576813"}]}]}]}
Synonyms	NIP3
Proteins	BNIP3_HUMAN
NCBI Gene ID	664
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BNIP3 has 15,344 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 128 datasets.

Click the + buttons to view associations for BNIP3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BNIP3 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 BNIP3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with BNIP3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BNIP3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BNIP3 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 BNIP3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BNIP3 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 BNIP3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of BNIP3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BNIP3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BNIP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BNIP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BNIP3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BNIP3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BNIP3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BNIP3 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 BNIP3 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 BNIP3 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 BNIP3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BNIP3 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 BNIP3 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 BNIP3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BNIP3 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 BNIP3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BNIP3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.