PLEKHM1 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH)
Name	pleckstrin homology domain containing, family M (with RUN domain) member 1
Description	The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLEKHM1 functions as a multivalent adaptor protein at the lysosome, integrating the endocytic and autophagic pathways. It directly interacts with the HOPS complex and engages autophagosomes via a conserved LC3‐interacting region (LIR), while binding the small GTPase Rab7 to ensure efficient fusion of endosomes and autophagosomes with lysosomes for cargo degradation. Loss of PLEKHM1 disrupts these fusion events, impairing autophagic flux and leading to the accumulation of cellular cargo, as demonstrated by defects in endocytic cargo degradation and clearance of protein aggregates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn osteoclasts, PLEKHM1 is critical for bone resorption by regulating vesicular trafficking processes essential for ruffled border formation. Mutations in this gene interfere with its colocalization with Rab7 on late endosomal/lysosomal vesicles, leading to defects in vesicle acidification and impaired secretion of tartrate‐resistant acid phosphatase (TRACP). These disruptions in vesicular transport underlie defective osteoclast-osteoblast cross-talk and manifest as osteopetrotic phenotypes observed in both human patients and animal models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its homeostatic functions, PLEKHM1 is also exploited by pathogens and is subject to dynamic regulatory control. The intracellular bacterium Salmonella targets PLEKHM1 via its effector SifA, manipulating the Rab7–HOPS machinery to mobilize host membranes for the formation of the Salmonella-containing vacuole, ultimately supporting bacterial proliferation. Furthermore, PLEKHM1 activity is modulated by phosphorylation through mTOR and ERK2, thereby linking membrane fusion at the lysosome to growth factor and nutrient signals. Perturbations in these regulatory pathways—exemplified by MYBL1-mediated control in vascular endothelial cells—further highlight the role of PLEKHM1 in maintaining cellular homeostasis, with implications for atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Keisuke Tabata, Kohichi Matsunaga, Ayuko Sakane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-06-0495"}], "href": "https://doi.org/10.1091/mbc.E10-06-0495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20943950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20943950"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David G McEwan, Doris Popovic, Andrea Gubas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.11.006"}], "href": "https://doi.org/10.1016/j.molcel.2014.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25498145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25498145"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David G McEwan, Ivan Dikic "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHM1: Adapting to life at the lysosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2015.1034419"}], "href": "https://doi.org/10.1080/15548627.2015.1034419"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25905573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25905573"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andrea Gubas, Christina Karantanou, Doris Popovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.14041"}], "href": "https://doi.org/10.1002/1873-3468.14041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33452816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33452816"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Liesbeth Van Wesenbeeck, Paul R Odgren, Fraser P Coxon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI30328"}], "href": "https://doi.org/10.1172/JCI30328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17404618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17404618"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andrea Del Fattore, Rachele Fornari, Liesbeth Van Wesenbeeck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1359/jbmr.071107"}], "href": "https://doi.org/10.1359/jbmr.071107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17997709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17997709"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yentl Huybrechts, Wim Van Hul "}, {"type": "b", "children": [{"type": "t", "text": "Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2022.116520"}], "href": "https://doi.org/10.1016/j.bone.2022.116520"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35981699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35981699"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "David G McEwan, Benjamin Richter, Beatrice Claudi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2014.11.011"}], "href": "https://doi.org/10.1016/j.chom.2014.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25500191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25500191"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shi-Ao Ding, Hao Liu, Rui Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of MYBL1 in endothelial cells contributes to atherosclerosis by repressing PLEKHM1-inducing autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Toxicol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10565-024-09873-6"}], "href": "https://doi.org/10.1007/s10565-024-09873-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38797732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38797732"}]}]}]}
Synonyms	B2, OPTB6, AP162, OPTA3
Proteins	PKHM1_HUMAN
NCBI Gene ID	9842
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PLEKHM1 has 7,489 functional associations with biological entities spanning 9 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, sequence feature) extracted from 108 datasets.

Click the + buttons to view associations for PLEKHM1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 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 PLEKHM1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PLEKHM1 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 PLEKHM1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PLEKHM1 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 PLEKHM1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PLEKHM1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PLEKHM1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PLEKHM1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PLEKHM1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PLEKHM1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PLEKHM1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PLEKHM1 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 PLEKHM1 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 PLEKHM1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PLEKHM1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PLEKHM1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PLEKHM1 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 PLEKHM1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PLEKHM1 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 PLEKHM1 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 PLEKHM1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PLEKHM1 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 PLEKHM1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PLEKHM1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PLEKHM1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PLEKHM1 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 PLEKHM1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PLEKHM1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of PLEKHM1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of PLEKHM1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.