BOK Gene

Name	BCL2-related ovarian killer
Description	The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes. Studies in rat show that this protein has restricted expression in reproductive tissues, interacts strongly with some antiapoptotic BCL2 proteins, not at all with proapoptotic BCL2 proteins, and induces apoptosis in transfected cells. Thus, this protein represents a proapoptotic member of the BCL2 family. [provided by RefSeq, Sep 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BOK (BCL‐2–related ovarian killer) is emerging as a multifunctional regulator whose activities extend beyond a simple pro‐apoptotic role. Several studies have shown that BOK can act as an unconventional effector of mitochondrial outer membrane permeabilization (MOMP) and trigger apoptosis even in the absence of the canonical mediators BAX and BAK, with its activity being largely governed at the level of protein stability via the endoplasmic reticulum–associated degradation machinery (involving ubiquitylation by AMFR/gp78)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In certain contexts, such as DNA damage where p53 is activated, BOK can be induced and may substitute for BAX to promote cytochrome c release"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while its transcriptional regulation by factors including E2F1 further underscores its role as a cell cycle–regulated pro‐apoptotic molecule."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond apoptosis, BOK has been implicated in other cellular processes. In trophoblast cells, for instance, BOK is upregulated by ceramide signaling and participates in the induction of mitochondrial fission during endoplasmic reticulum stress—a process that appears to contribute to autophagy and cell death in preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In neuronal systems, however, BOK may exert a neuroprotective function by helping to preserve mitochondrial bioenergetics and calcium homeostasis, as indicated by increased sensitivity to stress in its absence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, emerging evidence suggests that BOK can influence cellular metabolism by positively regulating enzymes involved in nucleotide biosynthesis, thereby linking its expression to proliferative control and chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In vivo studies further imply that BOK’s function may be context dependent. While its loss does not necessarily confer overt developmental defects—possibly because of functional redundancy with other BCL‐2 family members"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "—its deficiency or altered expression can impact stress responses and disease progression. For example, in models of hepatocarcinogenesis, reduced induction of pro‐apoptotic proteins occurs in the absence of BOK"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in lung adenocarcinoma BOK downregulation is associated with more aggressive disease features and reduced overall survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, although the precise mechanisms remain an area of active investigation, early evidence also supports the idea that BOK may have additional yet unconventional roles given its broad tissue distribution and regulation under distinct stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the context‐dependent and pleiotropic functions of BOK in regulating apoptosis, mitochondrial dynamics, autophagy, and cellular metabolism.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fabien Llambi, Yue-Ming Wang, Bernadette Victor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.02.026"}], "href": "https://doi.org/10.1016/j.cell.2016.02.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26949185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26949185"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marcos A Carpio, Michael Michaud, Wenping Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1421063112"}], "href": "https://doi.org/10.1073/pnas.1421063112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26015568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26015568"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alexander G Yakovlev, Simone Di Giovanni, Geping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BOK and NOXA are essential mediators of p53-dependent apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M313526200"}], "href": "https://doi.org/10.1074/jbc.M313526200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15102863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15102863"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jose M Rodriguez, Michele A Glozak, Yihong Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bok, Bcl-2-related Ovarian Killer, Is Cell Cycle-regulated and Sensitizes to Stress-induced Apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M604705200"}], "href": "https://doi.org/10.1074/jbc.M604705200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16772296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16772296"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jonathan Ausman, Joelcio Abbade, Leonardo Ermini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ceramide-induced BOK promotes mitochondrial fission in preeclampsia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0360-0"}], "href": "https://doi.org/10.1038/s41419-018-0360-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29463805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29463805"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Manpreet Kalkat, Julia Garcia, Jessica Ebrahimi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Placental autophagy regulation by the BOK-MCL1 rheostat."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.26452"}], "href": "https://doi.org/10.4161/auto.26452"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24113155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24113155"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Beatrice D'Orsi, Tobias Engel, Shona Pfeiffer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bok Is Not Pro-Apoptotic But Suppresses Poly ADP-Ribose Polymerase-Dependent Cell Death Pathways and Protects against Excitotoxic and Seizure-Induced Neuronal Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3780-15.2016"}], "href": "https://doi.org/10.1523/JNEUROSCI.3780-15.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27098698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27098698"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rahul Srivastava, Zhipeng Cao, Christina Nedeva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1904523116"}], "href": "https://doi.org/10.1073/pnas.1904523116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31311867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31311867"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "F Ke, A Voss, J B Kerr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2011.210"}], "href": "https://doi.org/10.1038/cdd.2011.210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22281706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22281706"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tatiana Rabachini, Yuniel Fernandez-Marrero, Matteo Montani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BOK promotes chemical-induced hepatocarcinogenesis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-017-0008-0"}], "href": "https://doi.org/10.1038/s41418-017-0008-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29229991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29229991"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Erika Moravcikova, Evzen Krepela, Vera S Donnenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BOK displays cell death-independent tumor suppressor activity in non-small-cell lung carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.30906"}], "href": "https://doi.org/10.1002/ijc.30906"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28744854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28744854"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jacqualyn J Schulman, Laura M Szczesniak, Eric N Bunker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bok regulates mitochondrial fusion and morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-019-0327-4"}], "href": "https://doi.org/10.1038/s41418-019-0327-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30976095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30976095"}]}]}]}
Synonyms	BCL2L9, BOKL
Proteins	BOK_HUMAN
NCBI Gene ID	666
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BOK has 5,757 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 115 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

BOK Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by BOK gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK 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 BOK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with BOK gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BOK 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 BOK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BOK 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 BOK 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 BOK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BOK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BOK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BOK 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 BOK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BOK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BOK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BOK gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with BOK 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 BOK 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 BOK gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with BOK 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 BOK 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 BOK 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 BOK 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 BOK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BOK 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 BOK 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 BOK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BOK 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 BOK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BOK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with BOK gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.