ARHGAP22 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Rho GTPase activating proteins (ARHGAP)
Name	Rho GTPase activating protein 22
Description	This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGAP22 is a Rho GTPase‐activating protein that plays a crucial role in modulating Rac1 activity in diverse cellular contexts. In tumor cells, particularly melanoma, ARHGAP22 is activated downstream of Rho‐kinase signaling and serves to inactivate Rac1, thereby suppressing mesenchymal cell movement and favoring an amoeboid migratory mode [(1,2)]. At the biochemical level, ARHGAP22 contains an N‐terminal pleckstrin homology domain that is essential for binding 14–3–3 proteins; this interaction is enhanced following Akt‐mediated phosphorylation in response to insulin and growth factors, ultimately modulating cell motility [(3,4)]. In the central nervous system, ARHGAP22 is critical for maintaining proper Rac1 activity: its loss leads to Rac1 hyperactivity, increased dendritic spine density, impairments in synaptic structure and plasticity, and consequent deficits in learning and memory [(5)]. In addition, genetic association studies have implicated ARHGAP22 in vascular pathology, as allelic variants in this gene are associated with enhanced endothelial cell angiogenesis and increased capillary permeability, contributing to the development and severity of diabetic retinopathy [(6,7)]. Epigenetic analyses also reveal ARHGAP22 promoter hypermethylation in invasive melanoma, suggesting that its altered expression may impact tumor progression [(8)]. Finally, differential DNA methylation patterns of ARHGAP22 have been observed in placental tissues from subjects with tetralogy of Fallot as well as in cells derived from patients with spinal muscular atrophy, and genetic variants in ARHGAP22 have been linked to type 2 diabetes progression, underscoring its potential as a biomarker in various pathologies [(9,10,11)].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "b", "children": [{"type": "t", "text": "References:"}]}, {"type": "t", "text": "<br>."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Victoria Sanz-Moreno, Gilles Gadea, Jessica Ahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rac activation and inactivation control plasticity of tumor cell movement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.09.043"}], "href": "https://doi.org/10.1016/j.cell.2008.09.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18984162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18984162"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniel R Croft, Michael F Olson "}, {"type": "b", "children": [{"type": "t", "text": "Regulating the conversion between rounded and elongated modes of cancer cell movement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2008.10.009"}], "href": "https://doi.org/10.1016/j.ccr.2008.10.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18977323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18977323"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shu-Hong Hu, Andrew E Whitten, Gordon J King, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The weak complex between RhoGAP protein ARHGAP22 and signal regulatory protein 14-3-3 has 1:2 stoichiometry and a single peptide binding mode."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0041731"}], "href": "https://doi.org/10.1371/journal.pone.0041731"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22952583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22952583"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexander F Rowland, Mark Larance, William E Hughes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of RhoGAP22 as an Akt-dependent regulator of cell motility in response to insulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.05583-11"}], "href": "https://doi.org/10.1128/MCB.05583-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21969604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21969604"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anna Longatti, Luisa Ponzoni, Edoardo Moretto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Arhgap22 Disruption Leads to RAC1 Hyperactivity Affecting Hippocampal Glutamatergic Synapses and Cognition in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-021-02502-x"}], "href": "https://doi.org/10.1007/s12035-021-02502-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34455539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34455539"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yu-Chuen Huang, Jane-Ming Lin, Hui-Ju Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of diabetic retinopathy in a Taiwanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ophtha.2010.07.020"}], "href": "https://doi.org/10.1016/j.ophtha.2010.07.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21310492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21310492"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rong Li, Peng Chen, Jing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of ARHGAP22 gene polymorphisms with the risk of type 2 diabetic retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gene Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jgm.2960"}], "href": "https://doi.org/10.1002/jgm.2960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28544509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28544509"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Viktória Koroknai, István Szász, Hector Hernandez-Vargas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA hypermethylation is associated with invasive phenotype of malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.14047"}], "href": "https://doi.org/10.1111/exd.14047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31602702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31602702"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "R Bahado-Singh, S Vishweswaraiah, N K Mishra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Placental DNA methylation changes in detection of tetralogy of Fallot."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ultrasound Obstet Gynecol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/uog.20292"}], "href": "https://doi.org/10.1002/uog.20292"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30977211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30977211"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "M A Maretina, K R Valetdinova, N A Tsyganova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of specific gene methylation patterns during motor neuron differentiation from spinal muscular atrophy patient-derived iPSC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2021.146109"}], "href": "https://doi.org/10.1016/j.gene.2021.146109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34871761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34871761"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jing Li, Jiachen Wei, Pengcheng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.13399"}], "href": "https://doi.org/10.18632/oncotarget.13399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27863428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27863428"}]}]}]}
Synonyms	RHOGAP22
Proteins	RHG22_HUMAN
NCBI Gene ID	58504
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARHGAP22 has 6,661 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 125 datasets.

Click the + buttons to view associations for ARHGAP22 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 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 ARHGAP22 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARHGAP22 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 ARHGAP22 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARHGAP22 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 ARHGAP22 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARHGAP22 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 ARHGAP22 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ARHGAP22 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARHGAP22 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARHGAP22 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ARHGAP22 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ARHGAP22 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 ARHGAP22 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 ARHGAP22 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing ARHGAP22 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARHGAP22 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARHGAP22 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with ARHGAP22 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ARHGAP22 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 ARHGAP22 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 ARHGAP22 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ARHGAP22 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ARHGAP22 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 ARHGAP22 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 ARHGAP22 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARHGAP22 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 ARHGAP22 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 ARHGAP22 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARHGAP22 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 ARHGAP22 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ARHGAP22 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.