APEX2 Gene

HGNC Family	Zinc fingers
Name	APEX nuclease (apurinic/apyrimidinic endonuclease) 2
Description	Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n APEX2, a secondary mammalian apurinic/apyrimidinic endonuclease, plays critical roles in DNA repair and genomic maintenance. Although its intrinsic AP‐endonuclease activity is relatively weak compared with APEX1, APEX2 exhibits robust 3′–5′ exonuclease and 3′-phosphodiesterase functions that facilitate the processing of 3′-blocked DNA termini and mismatched nucleotides (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In BRCA2-deficient cells, for instance, the apurinic endonuclease activity and PCNA-binding domain of APEX2 become essential, such that their inhibition results in synthetic lethality when combined with BRCA1/BRCA2 loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the adaptive immune system, APEX2 contributes to the formation of DNA double-strand breaks required for antibody diversification; it is implicated in both class switch recombination and somatic hypermutation via its 3′–5′ exonuclease activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Furthermore, APEX2 expression is upregulated during late S phase, where it interacts with PCNA to support postreplicative base excision repair; loss of APEX2 in murine models leads to cell cycle delays and defects in lymphopoiesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Aberrant regulation and genomic alterations of APEX2 have also been documented in several cancer types, suggesting its potential utility as a biomarker in tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies indicate that APEX2 is an important mediator of DNA end processing whose activities not only safeguard genome integrity but also facilitate error-prone processes essential for immune diversification.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masood Z Hadi, Krzysztof Ginalski, Lam H Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/jmbi.2001.5382"}], "href": "https://doi.org/10.1006/jmbi.2001.5382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11866537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11866537"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peter Burkovics, Valeria Szukacsov, Ildiko Unk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkl259"}], "href": "https://doi.org/10.1093/nar/gkl259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16687656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16687656"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kristen E Mengwasser, Richard O Adeyemi, Yumei Leng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2018.12.008"}], "href": "https://doi.org/10.1016/j.molcel.2018.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30686591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30686591"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeroen E J Guikema, Erin K Linehan, Daisuke Tsuchimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20071289"}], "href": "https://doi.org/10.1084/jem.20071289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18025127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18025127"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shahnaz Masani, Li Han, Kefei Yu "}, {"type": "b", "children": [{"type": "t", "text": "Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00026-13"}], "href": "https://doi.org/10.1128/MCB.00026-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23382073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23382073"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zahra Sabouri, Il-Mi Okazaki, Reiko Shinkura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/intimm/dxp061"}], "href": "https://doi.org/10.1093/intimm/dxp061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19556307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19556307"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yasuhito Ide, Daisuke Tsuchimoto, Yohei Tominaga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the genomic structure and expression of the mouse Apex2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0888-7543(02)00009-5"}], "href": "https://doi.org/10.1016/s0888-7543(02"}, {"type": "t", "text": "00009-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12573260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12573260"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yasuhito Ide, Daisuke Tsuchimoto, Yohei Tominaga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-04-1476"}], "href": "https://doi.org/10.1182/blood-2004-04-1476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15319281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15319281"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Katherine A Jensen, Xinghua Shi, Shan Yan "}, {"type": "b", "children": [{"type": "t", "text": "Genomic alterations and abnormal expression of APE2 in multiple cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-60656-5"}], "href": "https://doi.org/10.1038/s41598-020-60656-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32111912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32111912"}]}]}]}
Synonyms	APE2, XTH2, APEXL2, ZGRF2
Proteins	APEX2_HUMAN
NCBI Gene ID	27301
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

APEX2 has 5,750 functional associations with biological entities spanning 8 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) extracted from 109 datasets.

Click the + buttons to view associations for APEX2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of APEX2 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 APEX2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with APEX2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with APEX2 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 APEX2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of APEX2 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 APEX2 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 APEX2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing APEX2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of APEX2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing APEX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing APEX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing APEX2 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 APEX2 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 APEX2 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 APEX2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with APEX2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with APEX2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 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 APEX2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with APEX2 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 APEX2 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 APEX2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of APEX2 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 APEX2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with APEX2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.