PLEKHG5 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH)
Name	pleckstrin homology domain containing, family G (with RhoGef domain) member 5
Description	This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLEKHG5, a Rho-specific guanine nucleotide exchange factor, plays a critical role in the nervous system. Mutations in the PLEKHG5 gene have been identified in patients with severe lower motor neuron disease as well as in cases of intermediate Charcot–Marie–Tooth disease, where homozygous missense and premature stop codon mutations compromise its normal function. In neuronal cells, wild‐type PLEKHG5 normally activates the nuclear factor κB pathway and is thought to regulate essential processes such as axon terminal autophagy; in contrast, mutant forms exhibit altered stability, mislocalization, and aggregate formation, all of which may contribute to neurodegeneration and defective nerve conduction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in the peripheral nervous system, PLEKHG5 has been implicated in tumor biology. Studies in gliomas have demonstrated that PLEKHG5 is involved in tumor cell migration, invasion, and angiogenesis. Functional disruption of PLEKHG5 in glioblastoma models, using CRISPR/Cas9‐mediated knockout, leads to morphological changes such as loss of filopodia and impaired autophagic flux. Notably, these defects can be at least partially rescued by the expression of a constitutively active RAB26, implicating a downstream signaling cascade from PLEKHG5 through RAB26 to transcriptional regulators such as NF‐κB that ultimately modulate cell survival and chemotherapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies have further illuminated the molecular basis of PLEKHG5 function. Known also as Syx in some contexts, PLEKHG5 contains a pleckstrin homology domain that is critical for its membrane localization and interaction with regulatory proteins such as 14-3-3. Recent work combining protein expression, purification, and molecular dynamics simulations has provided novel insights into how phosphorylation-dependent interactions and membrane association regulate its guanine nucleotide exchange activity, thereby contributing to the precise spatial and temporal control of RhoA signaling during cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabelle Maystadt, René Rezsöhazy, Martine Barkats, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/518900"}], "href": "https://doi.org/10.1086/518900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17564964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17564964"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hamid Azzedine, Petra Zavadakova, Violaine Planté-Bordeneuve, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt274"}], "href": "https://doi.org/10.1093/hmg/ddt274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23777631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23777631"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hyeon Jin Kim, Young Bin Hong, Jin-Mo Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Orphanet J Rare Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1750-1172-8-104"}], "href": "https://doi.org/10.1186/1750-1172-8-104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23844677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23844677"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhongbo Chen, Reza Maroofian, A Nazlı Başak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel variants broaden the phenotypic spectrum of PLEKHG5-associated neuropathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ene.14649"}], "href": "https://doi.org/10.1111/ene.14649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33220101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33220101"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mingyu Qian, Zihang Chen, Shaobo Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHG5 is a novel prognostic biomarker in glioma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10147-019-01503-0"}], "href": "https://doi.org/10.1007/s10147-019-01503-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31309383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31309383"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kaya Elisa Witte, Carsten Slotta, Melanie Lütkemeyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-77958-3"}], "href": "https://doi.org/10.1038/s41598-020-77958-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33318498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33318498"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ryan J Boyd, Tien L Olson, James D Zook, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202101808RR"}], "href": "https://doi.org/10.1096/fj.202101808RR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35639414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35639414"}]}]}]}
Synonyms	CMTRIC, GEF720, TECH, DSMA4, SYX
Proteins	PKHG5_HUMAN
NCBI Gene ID	57449
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PLEKHG5 has 4,745 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 107 datasets.

Click the + buttons to view associations for PLEKHG5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PLEKHG5 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 PLEKHG5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PLEKHG5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PLEKHG5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PLEKHG5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PLEKHG5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PLEKHG5 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PLEKHG5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PLEKHG5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PLEKHG5 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 PLEKHG5 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 PLEKHG5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PLEKHG5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PLEKHG5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PLEKHG5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PLEKHG5 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 PLEKHG5 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 PLEKHG5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PLEKHG5 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PLEKHG5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PLEKHG5 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 PLEKHG5 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 PLEKHG5 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 PLEKHG5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PLEKHG5 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 PLEKHG5 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 PLEKHG5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PLEKHG5 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 PLEKHG5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PLEKHG5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PLEKHG5 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 PLEKHG5 from the GeneSigDB Published Gene Signatures dataset.