AIFM2 Gene

Name	apoptosis-inducing factor, mitochondrion-associated, 2
Description	This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Apoptosis-inducing factor mitochondria-associated 2 (AIFM2), also known as FSP1 or PRG3, is a multifunctional protein that plays a pivotal role in regulating cell fate under stress conditions. In cancer cells, AIFM2 has been identified as an endogenous ferroptosis suppressor that blocks erastin-, sorafenib-, and RSL3-induced ferroptotic cell death by engaging endosomal sorting complexes required for transport (ESCRT)-III to promote plasma membrane repair, a mechanism independent of the canonical ubiquinol antioxidant pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Biochemical analyses reveal that AIFM2 is a flavoprotein with NAD(P)H oxidoreductase activity whose redox function is modulated by the mutually exclusive binding of DNA and its reducing coenzyme. In this context, DNA binding suppresses its redox activity, thereby modulating the production of reactive oxygen species and influencing survival signaling cascades such as those mediated by Ras, NF-κB, or AP-1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Under conditions of oxidative stress, such as doxorubicin treatment, reactive aldehyde species (e.g., 4-hydroxy-2-nonenal) adduct critical residues on AIFM2, diminishing its NADH oxidoreductase function and promoting its translocation from mitochondria—a process that facilitates apoptosis in cardiac tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In certain cancer contexts, treatment with agents like HUHS1015 induces nuclear accumulation of AIFM2, which correlates with caspase-independent apoptotic cell death, highlighting yet another facet of its role in programmed cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, regulatory pathways involving non-coding RNAs—such as the MEG3/miR-214/AIFM2 axis—further implicate AIFM2 in integrating cellular stress signals to promote apoptosis in pluripotent cells, reflecting its multifaceted involvement in stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings support a model in which AIFM2 functions as a critical regulator balancing ferroptotic resistance and caspase-independent apoptosis through its redox activity, membrane repair mechanisms, and interactions with nucleic acids. This mechanistic plasticity renders AIFM2 a promising target for therapeutic interventions in diverse diseases including cancer and cardiovascular disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Enyong Dai, Wenlong Zhang, Dan Cong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AIFM2 blocks ferroptosis independent of ubiquinol metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.01.066"}], "href": "https://doi.org/10.1016/j.bbrc.2020.01.066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31964528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31964528"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ker R Marshall, Min Gong, Leigh Wodke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M414018200"}], "href": "https://doi.org/10.1074/jbc.M414018200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15958387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15958387"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Min Gong, Sam Hay, Ker R Marshall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA binding suppresses human AIF-M2 activity and provides a connection between redox chemistry, reactive oxygen species, and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703713200"}], "href": "https://doi.org/10.1074/jbc.M703713200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17711848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17711848"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sumitra Miriyala, Chadinee Thippakorn, Luksana Chaiswing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2015.12.002"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2015.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26689472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26689472"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pengfei Hao, Beichen Ding, Lingshu Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression patterns of sea urchins (Strongylocentrotus intermedius) exposed to different combinations of temperature and hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comp Biochem Physiol Part D Genomics Proteomics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cbd.2021.100953"}], "href": "https://doi.org/10.1016/j.cbd.2021.100953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34942521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34942521"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Junkwon Cho, Rika Teshigawara, Masahiro Kameda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nucleus-localized adiponectin is survival gatekeeper through miR-214-mediated AIFM2 regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12658"}], "href": "https://doi.org/10.1111/gtc.12658"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30474186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30474186"}]}]}]}
Synonyms	AMID, PRG3
Proteins	AIFM2_HUMAN
NCBI Gene ID	84883
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AIFM2 has 6,361 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 116 datasets.

Click the + buttons to view associations for AIFM2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AIFM2 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 AIFM2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AIFM2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AIFM2 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 AIFM2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AIFM2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AIFM2 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 AIFM2 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 AIFM2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AIFM2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AIFM2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AIFM2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 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 AIFM2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AIFM2 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 AIFM2 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 AIFM2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AIFM2 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 AIFM2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with AIFM2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AIFM2 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 AIFM2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of AIFM2 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 AIFM2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.