ARHGAP15 Gene

HGNC Family	Rho GTPase activating proteins (ARHGAP), Pleckstrin homology domain containing (PLEKH)
Name	Rho GTPase activating protein 15
Description	RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGAP15 is a Rho GTPase‐activating protein that primarily downregulates Rac1 activity, thereby serving as a critical negative regulator of actin cytoskeletal dynamics in diverse cellular contexts. In the nervous system, ARHGAP15 modulates the actin dynamics underlying neuritogenesis, dendritic branching, and synaptic formation; loss or reduced activity of ARHGAP15 results in Rac1 hyperactivation, which leads to impaired axonal elongation, reduced dendritic complexity, and an imbalance in inhibitory versus excitatory synapse formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In immune cells, particularly neutrophils, ARHGAP15 functions to negatively modulate Rac1‐dependent activities. Its absence enhances chemotaxis, phagocytosis, and reactive oxygen species production, thereby improving bacterial clearance and survival during sepsis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, ARHGAP15 acts as a tumor suppressor. Reduced expression of ARHGAP15 is associated with enhanced cell proliferation, migration, and invasion in colorectal and breast carcinomas, while its overexpression can activate the PTEN/AKT/FOXO1 signaling axis and counteract oncogenic processes. Moreover, in glioma cells the transcription factor FOXP3 upregulates ARHGAP15, leading to Rac1 inactivation and suppression of epithelial–mesenchymal transition markers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in the nervous and immune systems and in tumorigenesis, genetic studies have linked ARHGAP15 polymorphisms to susceptibility for diverticular disease, suggesting that alterations in ARHGAP15 expression or function may impact colonic neuromuscular properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In livestock, variants in ARHGAP15 have been associated with trypanotolerance, implying that this gene may influence the regulation of immune responses against infectious agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, ARHGAP15 is regulated by upstream effectors such as Pak1/2 via an interaction through its pleckstrin homology domain; this interaction leads to a mutual inhibition that fine-tunes both Rac1 activity and Pak kinase signaling, reinforcing ARHGAP15’s dual negative role in Rac-dependent pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Notably, studies on its structural features, including nucleotide-independent binding to Rac1 mediated by a novel motif, further support its specific function as a regulator of Rac1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Valentina Zamboni, Maria Armentano, Gaia Berto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperactivity of Rac1-GTPase pathway impairs neuritogenesis of cortical neurons by altering actin dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-25354-3"}], "href": "https://doi.org/10.1038/s41598-018-25354-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29740022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29740022"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Valentina Zamboni, Maria Armentano, Gabriella Sarò, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of ArhGAP15 results in hyperactive Rac1, affects the architecture and function of hippocampal inhibitory neurons and causes cognitive deficits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep34877"}], "href": "https://doi.org/10.1038/srep34877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27713499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27713499"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carlotta Costa, Giulia Germena, Erica L Martin-Conte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-12-324756"}], "href": "https://doi.org/10.1182/blood-2010-12-324756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21551229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21551229"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shengli Pan, Yingying Deng, Jun Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of ARHGAP15 promotes the development of colorectal cancer through PTEN/AKT/FOXO1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0707-6"}], "href": "https://doi.org/10.1038/s41419-018-0707-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29867200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29867200"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kiyoshi Takagi, Yasuhiro Miki, Yoshiaki Onodera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARHGAP15 in Human Breast Carcinoma: A Potent Tumor Suppressor Regulated by Androgens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms19030804"}], "href": "https://doi.org/10.3390/ijms19030804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29534468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29534468"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhen Sun, Biao Zhang, Chen Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Forkhead box P3 regulates ARHGAP15 expression and affects migration of glioma cells through the Rac1 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.13118"}], "href": "https://doi.org/10.1111/cas.13118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27862679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27862679"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Snaevar Sigurdsson, Kristjan F Alexandersson, Patrick Sulem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms15789"}], "href": "https://doi.org/10.1038/ncomms15789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28585551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28585551"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Michael Camilleri, Robert S Sandler, Anne F Peery "}, {"type": "b", "children": [{"type": "t", "text": "Etiopathogenetic Mechanisms in Diverticular Disease of the Colon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Gastroenterol Hepatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jcmgh.2019.07.007"}], "href": "https://doi.org/10.1016/j.jcmgh.2019.07.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31351939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31351939"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Isabel Álvarez, Lucía Pérez-Pardal, Amadou Traoré, et al. "}, {"type": "b", "children": [{"type": "t", "text": "African Cattle do not Carry Unique Mutations on the Exon 9 of the ARHGAP15 Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anim Biotechnol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10495398.2015.1053606"}], "href": "https://doi.org/10.1080/10495398.2015.1053606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26515718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26515718"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Harry Noyes, Andy Brass, Isaiah Obara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1013486108"}], "href": "https://doi.org/10.1073/pnas.1013486108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21593421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21593421"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Maria Radu, Sonali J Rawat, Alexander Beeser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ArhGAP15, a Rac-specific GTPase-activating protein, plays a dual role in inhibiting small GTPase signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.459719"}], "href": "https://doi.org/10.1074/jbc.M113.459719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23760270"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23760270"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Mui Leng Seoh, Chong Han Ng, Jeffery Yong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ArhGAP15, a novel human RacGAP protein with GTPase binding property."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(03)00213-8"}], "href": "https://doi.org/10.1016/s0014-5793(03"}, {"type": "t", "text": "00213-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12650940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12650940"}]}]}]}
Synonyms	BM046
Proteins	RHG15_HUMAN
NCBI Gene ID	55843
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARHGAP15 has 4,700 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 109 datasets.

Click the + buttons to view associations for ARHGAP15 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARHGAP15 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 ARHGAP15 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARHGAP15 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARHGAP15 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 ARHGAP15 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARHGAP15 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 ARHGAP15 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 ARHGAP15 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARHGAP15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARHGAP15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARHGAP15 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with ARHGAP15 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ARHGAP15 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ARHGAP15 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ARHGAP15 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ARHGAP15 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 ARHGAP15 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 ARHGAP15 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 ARHGAP15 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARHGAP15 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 ARHGAP15 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 ARHGAP15 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARHGAP15 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 ARHGAP15 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ARHGAP15 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ARHGAP15 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 ARHGAP15 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.