AGAP3 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Ankyrin repeat domain containing (ANKRD), ArfGAPs
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 3
Description	This gene encodes an essential component of the N-methyl-D-aspartate (NMDA) receptor signaling complex which mediates long-term potentiation in synapses by linking activation of NMDA receptor to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking. The encoded protein contains an N-terminal GTPase-like domain, a pleckstrin homology domain, an ArfGAP domain and several C-terminal ankryn repeat domains. [provided by RefSeq, Apr 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AGAP3 is a multifunctional protein that plays a critical role in neuronal signal transduction and cellular homeostasis. In neurons, AGAP3 is a component of the NMDA receptor complex where, through its multiple signaling domains—including a GTPase‐like domain, a pleckstrin homology domain, and an ArfGAP domain—it couples NMDA receptor activation to downstream signaling cascades. Specifically, AGAP3 regulates both Ras/ERK and Arf6 signaling pathways, a process that is essential for the NMDA receptor‐mediated trafficking of AMPA receptors during long‐term potentiation (LTP) and synaptic plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In proteomic studies investigating cytoskeletal and microtubule–associated networks, AGAP3 has been identified as enriched in complexes with microtubule‐associated proteins such as CLIP2, suggesting that it may also help coordinate cytoskeletal dynamics necessary for proper synaptic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n A short splicing variant of AGAP3, known as CRAG (CRMP5-associated GTPase), extends the functional repertoire of the AGAP3 gene. CRAG plays a protective role by promoting the degradation of aberrant or expanded polyglutamine proteins via the nuclear ubiquitin–proteasome pathway and by activating immediate early gene expression (such as c-Fos) through serum response factor (SRF) and AP-1 pathways. These actions contribute to enhanced cell survival under proteotoxic stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, evidence from cancer studies implicates the CRAG isoform in oncogenic processes. Overexpression of CRAG has been shown to upregulate activator protein-1 (AP-1) targets such as c-Jun, thereby stimulating cell proliferation and colony formation in colorectal cancer cells. These findings suggest that, beyond its neuronal functions, AGAP3 and its splice variant CRAG may contribute to tumorigenesis through AP-1-mediated transcriptional activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AGAP3 functions as an essential signaling mediator at the synapse by linking NMDA receptor activation to the regulation of AMPA receptor trafficking and synaptic plasticity, while its short splicing variant CRAG enhances cell survival in the context of proteotoxic stress and may promote oncogenic processes via AP-1 activation. These multifaceted roles underpin its importance in both neural function and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuko Oku, Richard L Huganir "}, {"type": "b", "children": [{"type": "t", "text": "AGAP3 and Arf6 regulate trafficking of AMPA receptors and synaptic plasticity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0341-13.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.0341-13.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23904596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23904596"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A M Strohecker, S Joshi, R Possemato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel autophagy regulator by high content shRNA screening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.23"}], "href": "https://doi.org/10.1038/onc.2015.23"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25772235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25772235"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shun Nagashima, Toshifumi Fukuda, Yuka Kubota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRMP5-associated GTPase (CRAG) protein protects neuronal cells against cytotoxicity of expanded polyglutamine protein partially via c-Fos-dependent activator protein-1 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.234997"}], "href": "https://doi.org/10.1074/jbc.M111.234997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21832068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21832068"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shun Nagashima, Keisuke Takeda, Isshin Shiiba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-56559-9"}], "href": "https://doi.org/10.1038/s41598-019-56559-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31882856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31882856"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dai Shimizu, Takaaki Masuda, Kuniaki Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRMP5-associated GTPase ("}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CRAG"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ") Is a Candidate Driver Gene for Colorectal Cancer Carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21873/anticanres.13084"}], "href": "https://doi.org/10.21873/anticanres.13084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30591445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30591445"}]}]}]}
Synonyms	CNT-G3, CRAG, AGAP-3, MRIP-1, CENTG3
Proteins	AGAP3_HUMAN
NCBI Gene ID	116988
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AGAP3 has 5,187 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for AGAP3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AGAP3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AGAP3 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 AGAP3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AGAP3 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 AGAP3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AGAP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AGAP3 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 AGAP3 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 AGAP3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AGAP3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AGAP3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AGAP3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 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 AGAP3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AGAP3 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 AGAP3 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 AGAP3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AGAP3 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 AGAP3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with AGAP3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AGAP3 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 AGAP3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of AGAP3 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 AGAP3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.