FGD4 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Rho guanine nucleotide exchange factors (ARHGEF), Zinc fingers
Name	FYVE, RhoGEF and PH domain containing 4
Description	This gene encodes a protein that is involved in the regulation of the actin cytoskeleton and cell shape. This protein contains an actin filament-binding domain, which together with its Dbl homology domain and one of its pleckstrin homology domains, can form microspikes. This protein can activate MAPK8 independently of the actin filament-binding domain, and it is also involved in the activation of CDC42 via the exchange of bound GDP for free GTP. The activation of CDC42 also enables this protein to play a role in mediating the cellular invasion of Cryptosporidium parvum, an intracellular parasite that infects the gastrointestinal tract. Mutations in this gene can cause Charcot-Marie-Tooth disease type 4H (CMT4H), a disorder of the peripheral nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FGD4, also known as frabin, encodes a guanine nucleotide exchange factor (GEF) that is highly specific for the small Rho GTPase Cdc42. The protein plays a critical role in the regulation of the actin cytoskeleton and cell signaling. In the peripheral nervous system, FGD4 is essential for proper Schwann cell function, myelination, and myelin maintenance; disruption of its activity—through mutations or genetic variation—leads to demyelinating neuropathies such as Charcot‐Marie–Tooth type 4H (CMT4H) (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In addition, common genetic markers within FGD4 have been associated with an increased risk of chemotherapy-induced peripheral neuropathy, highlighting its role as a modifier of neurotoxicity in cancer patients treated with agents such as paclitaxel."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its critical function in nerve biology, frabin mediates Cdc42-dependent changes in cell shape and endocytosis. It is recruited in response to signaling events, such as during Cryptosporidium parvum invasion, where activation of PI3 kinase leads to frabin accumulation at the host cell–pathogen interface and subsequent actin remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In prostate cancer models, elevated FGD4 expression enhances cell proliferation, migration, and mesenchymal marker expression via the Cdc42/PAK signaling cascade, whereas its inhibition results in reduced tumor cell motility and increased drug sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings highlight that FGD4/frabin is a pivotal modulator of Cdc42 activity that governs diverse cellular processes—from myelination and maintenance of peripheral nerve integrity to regulation of actin dynamics during cell migration and pathogen invasion. The multiple roles of FGD4 underscore its importance in both neurobiology and cancer biology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Valérie Delague, Arnaud Jacquier, Tarik Hamadouche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/518428"}], "href": "https://doi.org/10.1086/518428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17564959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17564959"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claudia Stendel, Andreas Roos, Tine Deconinck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/518770"}], "href": "https://doi.org/10.1086/518770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17564972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17564972"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michael Horn, Reto Baumann, Jorge A Pereira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/aws275"}], "href": "https://doi.org/10.1093/brain/aws275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23171661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23171661"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cécile Baudot, Clothilde Esteve, Christel Castro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Peripher Nerv Syst (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1529-8027.2012.00405.x"}], "href": "https://doi.org/10.1111/j.1529-8027.2012.00405.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22734899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22734899"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Young Se Hyun, Jinho Lee, Hye Jin Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ahg.12134"}], "href": "https://doi.org/10.1111/ahg.12134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26400421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26400421"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "R Michael Baldwin, Kouros Owzar, Hitoshi Zembutsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-12-1590"}], "href": "https://doi.org/10.1158/1078-0432.CCR-12-1590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22843789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22843789"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Siu W Lam, Charlotte N Frederiks, Tahar van der Straaten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2016.326"}], "href": "https://doi.org/10.1038/bjc.2016.326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27736846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27736846"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xian-Ming Chen, Patrick L Splinter, Pamela S Tietz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatidylinositol 3-kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of Cdc42."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M401592200"}], "href": "https://doi.org/10.1074/jbc.M401592200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15133042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15133042"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alexia Bossan, Richard Ottman, Thomas Andl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-018-5096-9"}], "href": "https://doi.org/10.1186/s12885-018-5096-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30558664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30558664"}]}]}]}
Synonyms	FRABP, CMT4H, ZFYVE6
Proteins	FGD4_HUMAN
NCBI Gene ID	121512
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FGD4 has 6,549 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 120 datasets.

Click the + buttons to view associations for FGD4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FGD4 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 FGD4 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 FGD4 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 FGD4 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 FGD4 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 FGD4 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 FGD4 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 FGD4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FGD4 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 FGD4 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 FGD4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FGD4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FGD4 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 FGD4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FGD4 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 FGD4 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 FGD4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with FGD4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FGD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FGD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FGD4 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 FGD4 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 FGD4 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 FGD4 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 FGD4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FGD4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FGD4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FGD4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with FGD4 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 FGD4 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 FGD4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving FGD4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FGD4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FGD4 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 FGD4 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 FGD4 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 FGD4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FGD4 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 FGD4 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 FGD4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FGD4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.