APC Gene

HGNC Family	Armadillo repeat containing (ARMC), Protein phosphatase 1 regulatory subunits (PPP1R)
Name	adenomatous polyposis coli
Description	This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The adenomatous polyposis coli (APC) gene encodes a multifunctional tumor suppressor protein that plays a central role in regulating canonical Wnt signaling by promoting the phosphorylation, ubiquitination, and subsequent proteasomal degradation of β‐catenin. In the normal intestinal epithelium, APC safeguards tissue homeostasis by ensuring that β‐catenin remains at low cytoplasmic levels; loss of APC function in long‐lived stem cells leads to rapid neoplastic transformation and adenoma formation, whereas its deletion in short‐lived transit‐amplifying cells results in stunted growth of microadenomas (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colorectal cancer, truncating mutations in APC are an early event that deregulate the Wnt pathway and initiate tumorigenesis; furthermore, restoration of APC in established tumors can induce differentiation and tumor regression, underscoring its essential role in tumor maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its canonical function in β‐catenin turnover, APC also influences gene expression programs critical for cellular differentiation and apoptosis. Loss of APC can trigger downstream alterations, such as the upregulation of histone deacetylase 2 (HDAC2), which contributes to the resistance to apoptosis observed in colonic cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the bone microenvironment, APC deletion in osteoblasts leads to constitutive β‐catenin activation, causing abnormal bone deposition and alterations in osteoclast formation, highlighting its role in coordinating cell differentiation in diverse tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies further clarify the role of APC in forming the destruction complex with β‐catenin and other scaffold proteins, elucidating how site‐specific phosphorylation events enhance its binding affinity for β‐catenin and promote its degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, emerging evidence suggests that C-terminally truncated APC proteins—commonly retained in human colorectal cancers—may confer gain-of-function properties that further drive tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, regulatory networks involving microRNAs that target APC mRNA have been implicated in reinforcing aberrant Wnt signaling and promoting stem cell–like behavior in certain cancers, indicating that precise modulation of APC expression is crucial for preventing tumor initiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Together, these studies underscore that APC is a pivotal regulator of β‐catenin signaling and cellular differentiation, with its loss or mutation being a critical initiating event in colorectal as well as other tissue-specific tumorigeneses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nick Barker, Rachel A Ridgway, Johan H van Es, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crypt stem cells as the cells-of-origin of intestinal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07602"}], "href": "https://doi.org/10.1038/nature07602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19092804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19092804"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takao Hinoi, Aytekin Akyol, Brian K Theisen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-2735"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-2735"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17942902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17942902"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lukas E Dow, Kevin P O'Rourke, Janelle Simon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.05.033"}], "href": "https://doi.org/10.1016/j.cell.2015.05.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26091037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26091037"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ping Zhu, Elke Martin, Jörg Mengwasser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1535-6108(04)00114-x"}], "href": "https://doi.org/10.1016/s1535-6108(04"}, {"type": "t", "text": "00114-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15144953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15144953"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sheri L Holmen, Cassandra R Zylstra, Aditi Mukherjee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of beta-catenin in postnatal bone acquisition."}]}, {"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.M501900200"}], "href": "https://doi.org/10.1074/jbc.M501900200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15802266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15802266"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nam-Chul Ha, Takashi Tonozuka, Jennifer L Stamos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2004.08.010"}], "href": "https://doi.org/10.1016/j.molcel.2004.08.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15327768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15327768"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lu Zhang, Jerry W Shay "}, {"type": "b", "children": [{"type": "t", "text": "Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djw332"}], "href": "https://doi.org/10.1093/jnci/djw332"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28423402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28423402"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Taichi Isobe, Shigeo Hisamori, Daniel J Hogan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.01977"}], "href": "https://doi.org/10.7554/eLife.01977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25406066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25406066"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun Yang, Wen Zhang, Paul M Evans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenomatous polyposis coli (APC) differentially regulates beta-catenin phosphorylation and ubiquitination in colon cancer cells."}]}, {"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.M600831200"}], "href": "https://doi.org/10.1074/jbc.M600831200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16798748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16798748"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mari Kuraguchi, Xiu-Ping Wang, Roderick T Bronson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenomatous polyposis coli (APC) is required for normal development of skin and thymus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.0020146"}], "href": "https://doi.org/10.1371/journal.pgen.0020146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17002498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17002498"}]}]}]}
Synonyms	GS, DP2.5, DP3, PPP1R46, BTPS2
Proteins	APC_HUMAN
NCBI Gene ID	324
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

APC has 15,210 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 120 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

APC 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 APC 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 APC 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 APC gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 APC 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 APC 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 APC 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 APC 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 APC 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 APC 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 APC 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 APC gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with APC gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with APC protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with APC 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 APC gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of APC 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 APC gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with APC gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of APC gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing APC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing APC 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 APC protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing APC protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with APC gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with APC gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with APC gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with APC 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 APC 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 APC gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving APC gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving APC gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with APC 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 APC 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 APC 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 APC gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with APC 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 APC 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 APC gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of APC 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 APC from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.