ARHGEF3 Gene

HGNC Family	Rho guanine nucleotide exchange factors (ARHGEF)
Name	Rho guanine nucleotide exchange factor (GEF) 3
Description	Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGEF3 is a RhoA‐specific guanine nucleotide exchange factor that has emerged as an important regulator in diverse biological processes. Genetic variants positioned upstream of the ARHGEF3 gene have been robustly associated with changes in mean platelet volume, underscoring its contribution to platelet function and vascular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In bone, variation in ARHGEF3 is linked to alterations in bone mineral density in women, implicating the RhoGTPase‐RhoGEF signaling pathway in the pathogenesis of osteoporosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and further supported by studies in osteoblast‐like cells where ARHGEF3 knockdown modulates the expression of key genes involved in bone metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of myeloid differentiation, treatment with histone deacetylase inhibitors induces increased expression of ARHGEF3 along with its translocation from the nucleus to the cytoplasm, where it activates the RhoA/Rho‐associated kinase cascade via downstream effectors such as SAPK/JNK and Elk1. These signaling events promote myeloid cell differentiation, highlighting a regulatory role for ARHGEF3 in acute myeloid leukemia cell maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have further revealed that ARHGEF3 contains a pleckstrin homology domain with distinct structural requirements for binding to specific phosphoinositides, suggesting that lipid interactions may critically influence its subcellular localization and activation status."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, genomic analyses have identified ARHGEF3 as a partner in gene fusion events in prostate cancer, although the functional implications of these rearrangements require further clarification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the findings indicate that ARHGEF3 functions as a pivotal modulator of RhoA signaling in a tissue‐ and context‐dependent manner, thereby influencing processes ranging from platelet activation and bone metabolism to cell differentiation and cancer biology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christa Meisinger, Holger Prokisch, Christian Gieger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies three loci associated with mean platelet volume."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.11.015"}], "href": "https://doi.org/10.1016/j.ajhg.2008.11.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19110211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19110211"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ben H Mullin, Richard L Prince, Ian M Dick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a role for the ARHGEF3 gene in postmenopausal osteoporosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.04.016"}], "href": "https://doi.org/10.1016/j.ajhg.2008.04.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18499081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18499081"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Benjamin H Mullin, Cyril Mamotte, Richard L Prince, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Influence of ARHGEF3 and RHOA knockdown on ACTA2 and other genes in osteoblasts and osteoclasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0098116"}], "href": "https://doi.org/10.1371/journal.pone.0098116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24840563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24840563"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Loredana D'Amato, Carmela Dell'Aversana, Mariarosaria Conte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/15592294.2014.988035"}], "href": "https://doi.org/10.4161/15592294.2014.988035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25494542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25494542"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nilmani Singh, Adriana Reyes-Ordoñez, Michael A Compagnone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-24639-y"}], "href": "https://doi.org/10.1038/s41467-021-24639-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34267198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34267198"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "I Teles Alves, T Hartjes, E McClellan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Next-generation sequencing reveals novel rare fusion events with functional implication in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.591"}], "href": "https://doi.org/10.1038/onc.2013.591"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24488012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24488012"}]}]}]}
Synonyms	GEF3, STA3, XPLN
Proteins	ARHG3_HUMAN
NCBI Gene ID	50650
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARHGEF3 has 8,073 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 118 datasets.

Click the + buttons to view associations for ARHGEF3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARHGEF3 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 ARHGEF3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARHGEF3 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 ARHGEF3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARHGEF3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARHGEF3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ARHGEF3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ARHGEF3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARHGEF3 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 ARHGEF3 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 ARHGEF3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARHGEF3 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 ARHGEF3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ARHGEF3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.