PMAIP1 Gene

Name	phorbol-12-myristate-13-acetate-induced protein 1
Description	This gene belongs to a pro-apoptotic subfamily within the BCL-2 protein family, referred to as the BCL-2 homology domain 3 (BH3)-only subfamily, which determine whether a cell commits to apoptosis. In response to death-inducing stimuli, BH3-only members inhibit the anti-apoptotic BCL-2 family members, which under steady-state conditions keep the multi-BH domain proteins BAX and BAK, in an inactive state. [provided by RefSeq, Aug 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPMAIP1, also known as Noxa, is a critical BH3‐only protein that acts as a central mediator of stress‐induced apoptosis. It is rapidly induced by various cellular insults such as hypoxia, DNA damage, and oncogenic stress. For example, under hypoxic conditions Noxa transcription is directly activated via HIF-1α, while genotoxic insults trigger both p53-dependent and -independent induction, leading to mitochondrial cytochrome c release and cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to transcriptional regulation, PMAIP1 activity is finely tuned by post-translational modifications and stress-responsive signaling. Proteasome inhibitors and agents that induce endoplasmic reticulum stress invoke an integrated stress response mediated by CREB/ATF factors, thereby upregulating PMAIP1 expression. Moreover, modifications such as phosphorylation by Cdk5 in the presence of glucose serve as a molecular toggle that sequesters Noxa in the cytosol and attenuates its apoptotic potential, underscoring its dynamic regulation in response to metabolic cues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PMAIP1 promotes cell death chiefly by binding to and neutralizing antiapoptotic Bcl-2 family members, particularly Mcl-1. In nutrient-deprived T cells, for instance, Noxa interacts with the labile Mcl-1 to sensitize cells to apoptosis, while in neuroblastoma cells it collaborates with other BH3-only proteins to trigger mitochondrial dysfunction. Similarly, in the context of cisplatin exposure, the activation of PMAIP1 participates in intricate signaling cascades that tip the balance away from survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, aberrant expression and regulation of PMAIP1 play dual roles in cancer biology by influencing both tumor suppression and chemoresistance. In malignancies such as mantle cell lymphoma and chronic lymphocytic leukemia, altered Noxa levels are associated with differential sensitivity to chemotherapeutic agents and BH3 mimetics, suggesting that modulation of its expression may overcome resistance. Furthermore, oncogenic signals—for example, those arising from deregulated Ras pathways—can induce PMAIP1 alongside autophagic regulators to constrain tumor growth, and novel agents like cannabidiol have been shown to trigger PMAIP1-dependent apoptosis in colorectal cancer cells, underscoring its emerging potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young-Woo Seo, Jin Na Shin, Kang Hee Ko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The molecular mechanism of Noxa-induced mitochondrial dysfunction in p53-mediated cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308785200"}], "href": "https://doi.org/10.1074/jbc.M308785200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14500711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14500711"}]}, {"type": "r", "ref": 2, "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": 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": "Qiuyan Wang, Helena Mora-Jensen, Marc A Weniger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells."}]}, {"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.0807611106"}], "href": "https://doi.org/10.1073/pnas.0807611106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19164757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19164757"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xazmin H Lowman, Maureen A McDonnell, Ashley Kosloske, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The proapoptotic function of Noxa in human leukemia cells is regulated by the kinase Cdk5 and by glucose."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.11.035"}], "href": "https://doi.org/10.1016/j.molcel.2010.11.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21145489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21145489"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nuno L Alves, Ingrid A M Derks, Erik Berk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2006.03.018"}], "href": "https://doi.org/10.1016/j.immuni.2006.03.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16782027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16782027"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "P Obexer, K Geiger, P F Ambros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.cdd.4402017"}], "href": "https://doi.org/10.1038/sj.cdd.4402017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16888645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16888645"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Andrew M Fribley, Benjamin Evenchik, Qinghua Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa."}]}, {"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.M604356200"}], "href": "https://doi.org/10.1074/jbc.M604356200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16928686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16928686"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura A Smit, Delfine Y H Hallaert, René Spijker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-05-021683"}], "href": "https://doi.org/10.1182/blood-2006-05-021683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17038534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17038534"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Patricia Pérez-Galán, Gaël Roué, Neus Villamor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-07-034173"}], "href": "https://doi.org/10.1182/blood-2006-07-034173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17227835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17227835"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mohamed Elgendy, Clare Sheridan, Gabriela Brumatti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2011.02.009"}], "href": "https://doi.org/10.1016/j.molcel.2011.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21353614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21353614"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Soyeon Jeong, Hye Kyeong Yun, Yoon A Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2019.01.011"}], "href": "https://doi.org/10.1016/j.canlet.2019.01.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30660647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30660647"}]}]}]}
Synonyms	NOXA
Proteins	APR_HUMAN
NCBI Gene ID	5366
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PMAIP1 has 14,178 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 PMAIP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PMAIP1 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 PMAIP1 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PMAIP1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PMAIP1 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 PMAIP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PMAIP1 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 PMAIP1 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 PMAIP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PMAIP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PMAIP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PMAIP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PMAIP1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PMAIP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 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 PMAIP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PMAIP1 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 PMAIP1 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 PMAIP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PMAIP1 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 PMAIP1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PMAIP1 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 PMAIP1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PMAIP1 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 PMAIP1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PMAIP1 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 PMAIP1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.