BCL2L12 Gene

Name	BCL2-like 12 (proline rich)
Description	This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BCL2L12, a recently characterized and atypical member of the Bcl‑2 family, plays a multifaceted role in tumor biology by modulating apoptotic signaling in a context‐dependent manner. In several malignancies—including glioblastoma and melanoma—it has been shown to impair postmitochondrial apoptosis by interfering with the activation of key effector caspases and by binding to p53, thereby promoting cell survival and therapy resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In melanoma, for example, a recurrent synonymous mutation in BCL2L12 leads to its enhanced mRNA and protein expression, increased binding to p53, and a more effective inhibition of UV‑induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Conversely, tumor‐suppressive microRNAs—such as miR‑125a‑5p in colon cancer and miR‑182‑5p in acute myeloid leukemia—directly target BCL2L12 to downregulate its expression and thereby restore apoptotic potential and reduce cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Alternative splicing of BCL2L12 also generates multiple transcript variants and protein isoforms whose differential expression contributes to its context‑dependent function in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Clinically, aberrant expression of BCL2L12 carries prognostic significance. In nasopharyngeal carcinoma and chronic lymphocytic leukemia, high BCL2L12 levels correlate with advanced disease and shorter overall survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", whereas in certain breast cancers its expression has been associated with favorable outcome and enhanced chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Furthermore, studies in genetically modified cells indicate that BCL2L12 may exert cell type–dependent pro‑ or anti‑apoptotic effects—for instance, its re‐expression restores DNA damage–induced apoptosis in IRF3/BCL2L12–deficient fibroblasts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Collectively, these findings underscore the versatile regulatory role of BCL2L12 in apoptosis and tumor progression and highlight its potential as both a prognostic biomarker and a therapeutic target in various human cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_fs", "start_ref": "10", "end_ref": "12"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "5"}, {"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jared J Gartner, Stephen C J Parker, Todd D Prickett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1304227110"}], "href": "https://doi.org/10.1073/pnas.1304227110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23901115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23901115"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexander H Stegh, Santosh Kesari, John E Mahoney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712034105"}], "href": "https://doi.org/10.1073/pnas.0712034105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18669646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18669646"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ming-Chang Yang, Joon-Khim Loh, Yi-Yang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy: a prospective combination of ABT-737 and TMZ for treating glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2015.2838"}], "href": "https://doi.org/10.3892/ijo.2015.2838"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25586056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25586056"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chia-Hua Chou, An-Kuo Chou, Ching-Chih Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.11.3.19051"}], "href": "https://doi.org/10.4161/cc.11.3.19051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22262180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22262180"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fotini M Kouri, Lisa A Hurley, Weston L Daniel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.257394.114"}], "href": "https://doi.org/10.1101/gad.257394.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25838542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25838542"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhiguo Tong, Nan Liu, Luoqiang Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via targeting BCL2, BCL2L12 and MCL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2015.07.036"}], "href": "https://doi.org/10.1016/j.biopha.2015.07.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26297542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26297542"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Suwei Zhang, Qiaoxin Zhang, Ganggang Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-182-5p regulates BCL2L12 and BCL2 expression in acute myeloid leukemia as a potential therapeutic target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2017.11.002"}], "href": "https://doi.org/10.1016/j.biopha.2017.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29136958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29136958"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Christos K Kontos, Andreas Scorilas "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning of novel alternatively spliced variants of BCL2L12, a new member of the BCL2 gene family, and their expression analysis in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.04.084"}], "href": "https://doi.org/10.1016/j.gene.2012.04.084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22664385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22664385"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Konstantina Mathioudaki, Andreas Scorilas, Alexandra Papadokostopoulou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/BC.2004.101"}], "href": "https://doi.org/10.1515/BC.2004.101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15493871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15493871"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ali Fendri, Christos K Kontos, Abdelmajid Khabir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCL2L12 is a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2119/molmed.2010.00056"}], "href": "https://doi.org/10.2119/molmed.2010.00056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21152697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21152697"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sotirios G Papageorgiou, Christos K Kontos, Vassiliki Pappa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel member of the BCL2 gene family, BCL2L12, is substantially elevated in chronic lymphocytic leukemia patients, supporting its value as a significant biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncologist (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/theoncologist.2010-0349"}], "href": "https://doi.org/10.1634/theoncologist.2010-0349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21737576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21737576"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yi Hong, Junwu Yang, Weibing Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of BCL2L12 leads to cisplatin resistance in MDA-MB-231 breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2008.09.008"}], "href": "https://doi.org/10.1016/j.bbadis.2008.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18930135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18930135"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Maroulio Talieri, Eleftherios P Diamandis, Nikos Katsaros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12783122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12783122"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Akira Nakajima, Keishiro Nishimura, Yukana Nakaima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutation concomitant with the disruption of the juxtaposed Irf3 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0905702106"}], "href": "https://doi.org/10.1073/pnas.0905702106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19617565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19617565"}]}]}]}
Proteins	B2L12_HUMAN
NCBI Gene ID	83596
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BCL2L12 has 5,497 functional associations with biological entities spanning 7 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA) extracted from 111 datasets.

Click the + buttons to view associations for BCL2L12 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BCL2L12 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 BCL2L12 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BCL2L12 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 BCL2L12 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing BCL2L12 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BCL2L12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BCL2L12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BCL2L12 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BCL2L12 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 BCL2L12 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 BCL2L12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BCL2L12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BCL2L12 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BCL2L12 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 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 BCL2L12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BCL2L12 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 BCL2L12 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 BCL2L12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BCL2L12 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 BCL2L12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BCL2L12 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with BCL2L12 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with BCL2L12 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 BCL2L12 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of BCL2L12 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.