AP2M1 Gene

Name	adaptor-related protein complex 2, mu 1 subunit
Description	This gene encodes a subunit of the heterotetrameric coat assembly protein complex 2 (AP2), which belongs to the adaptor complexes medium subunits family. The encoded protein is required for the activity of a vacuolar ATPase, which is responsible for proton pumping occurring in the acidification of endosomes and lysosomes. The encoded protein may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AP2M1, the μ‐subunit of the adaptor protein complex 2 (AP‐2), plays a central role in clathrin‐mediated endocytosis by recognizing canonical tyrosine‐based (YXXΦ) sorting motifs in a wide variety of cargo proteins and recruiting them into clathrin‐coated vesicles. Multiple studies demonstrate that AP2M1 is essential for the intracellular trafficking of both viral and cellular proteins. For example, AP2M1 binds a conserved YXXΦ motif in the hepatitis C virus core protein, thereby facilitating its recruitment to lipid droplets and subsequent delivery to the trans‐Golgi network—a critical step during viral assembly that is further regulated by kinases such as AAK1 and GAK."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, the entry of rabies virus into host cells requires AAK1‐mediated phosphorylation of AP2M1, which enables efficient clathrin‐dependent uptake."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in viral infection, AP2M1 is also critical for regulating the internalization and recycling of key cellular receptors. It mediates endocytic trafficking of proteins containing YXXΦ motifs such as IFITM3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", CD22"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and KIAA0319"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", as well as modulating receptors like TRKB whose coupling to AP2M1 can be disrupted by antidepressants."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, a recurrent de novo mutation (p.Arg170Trp) in AP2M1 has been linked to developmental and epileptic encephalopathies through its detrimental effect on transferrin uptake and synaptic vesicle recycling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted functions of AP2M1 in regulating the endocytosis of both pathogen‐derived and endogenous proteins. Its activity is fundamental not only to normal receptor turnover and signal modulation but also to the lifecycle of viruses that hijack the host endocytic machinery. The central role of AP2M1 in these processes makes it an attractive target for therapeutic interventions in infectious diseases and disorders associated with trafficking defects.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gregory Neveu, Rina Barouch-Bentov, Amotz Ziv-Av, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and targeting of an interaction between a tyrosine motif within hepatitis C virus core protein and AP2M1 essential for viral assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1002845"}], "href": "https://doi.org/10.1371/journal.ppat.1002845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22916011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22916011"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chong Wang, Jinliang Wang, Lei Shuai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Viruses (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/v12010045"}], "href": "https://doi.org/10.3390/v12010045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31905947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31905947"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui Jia, Fengwen Xu, Jin Qian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an endocytic signal essential for the antiviral action of IFITM3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12262"}], "href": "https://doi.org/10.1111/cmi.12262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24521078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24521078"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "BinuJoy John, Brantley R Herrin, Chander Raman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.7.3534"}], "href": "https://doi.org/10.4049/jimmunol.170.7.3534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646615"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Clotilde Levecque, Antonio Velayos-Baeza, Zoe G Holloway, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00630.2008"}], "href": "https://doi.org/10.1152/ajpcell.00630.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19419997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19419997"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Senem Merve Fred, Liina Laukkanen, Cecilia A Brunello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacologically diverse antidepressants facilitate TRKB receptor activation by disrupting its interaction with the endocytic adaptor complex AP-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.008837"}], "href": "https://doi.org/10.1074/jbc.RA119.008837"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31631060"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31631060"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ingo Helbig, Tania Lopez-Hernandez, Oded Shor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Mediated Endocytosis and Causes Developmental and Epileptic Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2019.04.001"}], "href": "https://doi.org/10.1016/j.ajhg.2019.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31104773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31104773"}]}]}]}
Synonyms	CLAPM1, AP50, mu2
Proteins	AP2M1_HUMAN
NCBI Gene ID	1173
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AP2M1 has 9,877 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for AP2M1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving AP2M1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 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 AP2M1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AP2M1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AP2M1 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 AP2M1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AP2M1 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 AP2M1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with AP2M1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AP2M1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AP2M1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AP2M1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AP2M1 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 AP2M1 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 AP2M1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AP2M1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AP2M1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AP2M1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AP2M1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving AP2M1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with AP2M1 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 AP2M1 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 AP2M1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AP2M1 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 AP2M1 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 AP2M1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AP2M1 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 AP2M1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with AP2M1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with AP2M1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.