ARHGAP12 Gene

HGNC Family	Rho GTPase activating proteins (ARHGAP), Pleckstrin homology domain containing (PLEKH)
Name	Rho GTPase activating protein 12
Description	This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may be involved in suppressing tumor formation by regulating cell invasion and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGAP12 is a Rac1‐specific GTPase–activating protein that plays multifaceted roles in regulating actin dynamics and cell signaling in diverse cellular contexts. In response to external cues such as hepatocyte growth factor, ARHGAP12 expression is transcriptionally suppressed, and its overexpression is sufficient to dampen Rac1 activity and thereby reduce cell scattering, adhesion, and invasion, indicating a critical inhibitory role in invasive growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In epithelial cells, ARHGAP12 has been identified as an essential component of the junctional complex that contributes to the maintenance of proper cell–cell adhesion and urothelial integrity, ensuring the establishment of a tight barrier."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " During efferocytosis, ARHGAP12 dynamically associates with phagocytic cups, where it is recruited via phosphatidylinositol‐4,5–bisphosphate to inactivate Rac1 in a spatially and temporally precise manner; its down‐regulation results in sustained Rac1 activity, aberrant actin organization, and delayed phagosome–lysosome fusion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the nervous system, ARHGAP12 localizes to the postsynaptic compartment where it negatively controls dendritic spine size and drives AMPA receptor endocytosis, preventing the premature maturation of excitatory synapses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, ARHGAP12 has been implicated in cancer biology: gene fusions involving ARHGAP12 (such as the BMX–ARHGAP fusion) have been detected in gastric cardia adenocarcinoma and its genetic alterations (including rare homozygous variants) have been identified in early‐onset colorectal cancer, suggesting a potential role in tumorigenesis and stem cell regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " In addition, interaction studies have demonstrated that ARHGAP12 associates with lipid‐binding regulators such as ORP2 to impact actin cytoskeletal arrangement, which in turn influences cell migration, adhesion, and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, cloning and molecular characterization of ARHGAP12 splice variants have revealed that the protein contains several conserved domains—including RhoGAP, SH3, PH, and WW domains—and is ubiquitously expressed, supporting its fundamental role in modulating Rho GTPase–dependent signaling pathways; its up‐regulation by statin treatment has even been linked to protective effects in models of arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Gentile, L D'Alessandro, L Lazzari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Met-driven invasive growth involves transcriptional regulation of Arhgap12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.173"}], "href": "https://doi.org/10.1038/onc.2008.173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18504429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18504429"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katia Monastyrskaya, Verónica Sánchez-Freire, Ali Hashemi Gheinani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2012.10.020"}], "href": "https://doi.org/10.1016/j.ajpath.2012.10.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23201090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23201090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miho Matsuda, Yuka Kobayashi, Sayuri Masuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization-based expression cloning."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.11.009"}], "href": "https://doi.org/10.1016/j.yexcr.2007.11.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18241859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18241859"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dong-Jun Bae, Junyoung Seo, Sang-Yeob Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ArhGAP12 plays dual roles in Stabilin-2 mediated efferocytosis: Regulates Rac1 basal activity and spatiotemporally turns off the Rac1 to orchestrate phagosome maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2019.07.003"}], "href": "https://doi.org/10.1016/j.bbamcr.2019.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31301364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31301364"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniel Schlam, Richard D Bagshaw, Spencer A Freeman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9623"}], "href": "https://doi.org/10.1038/ncomms9623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26465210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26465210"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "W Ba, M M Selten, J van der Raadt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.01.037"}], "href": "https://doi.org/10.1016/j.celrep.2016.01.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26854232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26854232"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiaofeng Xu, Lifang Xu, Feng Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel gene fusion (BMX-ARHGAP) in gastric cardia adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diagn Pathol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13000-014-0218-4"}], "href": "https://doi.org/10.1186/s13000-014-0218-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25499959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25499959"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tomas Tanskanen, Alexandra E Gylfe, Riku Katainen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic search for rare variants in Finnish early-onset colorectal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cancergen.2014.12.004"}], "href": "https://doi.org/10.1016/j.cancergen.2014.12.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25749350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25749350"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiao-Feng Xu, Feng Gao, Jian-Jiang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell Int (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12935-019-0847-5"}], "href": "https://doi.org/10.1186/s12935-019-0847-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31130822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31130822"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Henriikka Kentala, Annika Koponen, Annukka M Kivelä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of ORP2-knockout hepatocytes uncovers a novel function in actin cytoskeletal regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201700604R"}], "href": "https://doi.org/10.1096/fj.201700604R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29092904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29092904"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zhen Zhang, ChaoQun Wu, Shu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of ARHGAP12, a novel human rhoGAP gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1357-2725(01)00134-0"}], "href": "https://doi.org/10.1016/s1357-2725(01"}, {"type": "t", "text": "00134-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11854031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11854031"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Shun Tanimura, Mutsumi Nishida, Tatsunori Horie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fluvastatin prevents the development of arthritis in env-pX rats via up-regulation of Rho GTPase-activating protein 12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Pathol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexmp.2020.104454"}], "href": "https://doi.org/10.1016/j.yexmp.2020.104454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32422132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32422132"}]}]}]}
Proteins	RHG12_HUMAN
NCBI Gene ID	94134
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARHGAP12 has 7,335 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 121 datasets.

Click the + buttons to view associations for ARHGAP12 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ARHGAP12 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARHGAP12 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 ARHGAP12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARHGAP12 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARHGAP12 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 ARHGAP12 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARHGAP12 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 ARHGAP12 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 ARHGAP12 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARHGAP12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARHGAP12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARHGAP12 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 ARHGAP12 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 ARHGAP12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARHGAP12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ARHGAP12 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ARHGAP12 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ARHGAP12 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ARHGAP12 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 ARHGAP12 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 ARHGAP12 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 ARHGAP12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARHGAP12 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 ARHGAP12 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 ARHGAP12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARHGAP12 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 ARHGAP12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ARHGAP12 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ARHGAP12 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ARHGAP12 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ARHGAP12 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 ARHGAP12 from the GeneSigDB Published Gene Signatures dataset.