FGD1 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Zinc fingers, Rho guanine nucleotide exchange factors (ARHGEF)
Name	FYVE, RhoGEF and PH domain containing 1
Description	This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of the faciogenital dysplasia in Aarskog-Scott syndrome and a syndromatic form of X-linked cognitive disability. [provided by RefSeq, Jul 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42, thereby playing a central role in orchestrating actin cytoskeletal dynamics, cell shape modulation, and membrane trafficking. Studies have shown that FGD1 interacts directly with actin‐regulatory proteins such as cortactin and mAbp1, which contributes to the formation of dynamic actin structures—including lamellipodia and invadopodia—that mediate extracellular matrix degradation and promote invasive behavior in tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, FGD1 functions within signaling cascades downstream of activated Ras to modulate focal adhesion kinase activity and cell motility, with its expression levels correlating with tumor aggressiveness. In osteoblasts, FGD1 enhances Cdc42 activation and stimulates a signaling relay involving MLK3 and MAP kinases that is crucial for Runx2‐mediated differentiation and proper skeletal mineralization; disruption of this pathway is implicated in the skeletal abnormalities seen in Faciogenital Dysplasia (Aarskog–Scott syndrome)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, regulation of FGD1 protein turnover via ubiquitin-mediated degradation (dependent on conserved motifs) contributes to the refinement of its activity in controlling cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Complementary evidence further suggests that FGD1 supports plasma membrane–associated Cdc42 activation essential for cell polarization, even though it may be less critical for Golgi-associated Cdc42 regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, FGD1 serves as a multifunctional regulator that links Cdc42 activation with cytoskeletal remodeling, extracellular matrix turnover, developmental processes, and tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peng Hou, Lourdes Estrada, Andrew W Kinley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fgd1, the Cdc42 GEF responsible for Faciogenital Dysplasia, directly interacts with cortactin and mAbp1 to modulate cell shape."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddg209"}], "href": "https://doi.org/10.1093/hmg/ddg209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12913069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12913069"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Inmaculada Ayala, Giada Giacchetti, Giusi Caldieri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Faciogenital dysplasia protein Fgd1 regulates invadopodia biogenesis and extracellular matrix degradation and is up-regulated in prostate and breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-1980"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-1980"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19141649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19141649"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Weiguo Zou, Matthew B Greenblatt, Jae-Hyuck Shim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI59041"}], "href": "https://doi.org/10.1172/JCI59041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21965325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21965325"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Makio Hayakawa, Masahide Matsushima, Hiroshi Hagiwara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel insights into FGD3, a putative GEF for Cdc42, that undergoes SCF(FWD1/beta-TrCP)-mediated proteasomal degradation analogous to that of its homologue FGD1 but regulates cell morphology and motility differently from FGD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2443.2008.01168.x"}], "href": "https://doi.org/10.1111/j.1365-2443.2008.01168.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18363964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18363964"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wei Wu, Doudou Jing, Zibo Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.41279"}], "href": "https://doi.org/10.7150/thno.41279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32194840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32194840"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elisabeth Genot, Thomas Daubon, Vincenzo Sorrentino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGD1 as a central regulator of extracellular matrix remodelling--lessons from faciogenital dysplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.093419"}], "href": "https://doi.org/10.1242/jcs.093419"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22854039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22854039"}]}]}]}
Synonyms	MRXS16, AAS, FGDY, ZFYVE3
Proteins	FGD1_HUMAN
NCBI Gene ID	2245
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FGD1 has 5,767 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 115 datasets.

Click the + buttons to view associations for FGD1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FGD1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FGD1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FGD1 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 FGD1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with FGD1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FGD1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FGD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FGD1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FGD1 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 FGD1 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 FGD1 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 FGD1 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 FGD1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FGD1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FGD1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FGD1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of FGD1 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 FGD1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving FGD1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FGD1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FGD1 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 FGD1 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 FGD1 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 FGD1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FGD1 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 FGD1 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 FGD1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FGD1 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 FGD1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.