EHD2 Gene

HGNC Family	EF-hand domain containing
Name	EH-domain containing 2
Description	This gene encodes a member of the EH domain-containing protein family. These proteins are characterized by a C-terminal EF-hand domain, a nucleotide-binding consensus site at the N terminus and a bipartite nuclear localization signal. The encoded protein interacts with the actin cytoskeleton through an N-terminal domain and also binds to an EH domain-binding protein through the C-terminal EH domain. This interaction appears to connect clathrin-dependent endocytosis to actin, suggesting that this gene product participates in the endocytic pathway. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EH‐domain–containing protein 2 (EHD2) is a dynamin‐related ATPase with diverse roles in regulating plasma membrane dynamics. In multiple cell types, EHD2 stabilizes caveolae by confining these flask‐shaped invaginations at the cell surface and controlling their detachment via a tightly regulated ATPase cycle that involves ATP binding, oligomerization, and subsequent hydrolysis‐dependent release. This cycle is coordinated with conformational changes that are modulated by membrane phospholipids—including phosphatidylinositol 4,5‐bisphosphate (PIP2)—which govern its subcellular localization ("}, {"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": "\n In addition, EHD2 links endocytic processes with cytoskeletal dynamics by cooperating with actin‐binding partners such as EHBP1 and by modulating Rac1 activity to influence vesicular trafficking and cell motility ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "). Its functional contributions extend to skeletal muscle development, where direct binding to myoferlin is critical for proper myoblast fusion; loss or inhibition of EHD2 in this context leads to impaired membrane fusion events during myotube formation ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ")."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In adipocytes, EHD2 regulates fat metabolism by modulating caveolae‐dependent fatty acid uptake, thereby influencing lipid droplet size and overall lipid storage capacity ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "). Moreover, decreased expression of EHD2 in certain epithelial cancers—such as esophageal squamous cell carcinoma and breast cancer—is associated with enhanced cellular motility, increased invasive potential, and resistance to chemotherapy, supporting a putative tumor suppressor role in these contexts ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight that EHD2 is a central mediator of plasma membrane remodeling and endocytic recycling, wherein its ATP‐dependent activities—and interactions with both lipids and proteins—are crucial for maintaining cellular homeostasis in processes ranging from membrane tension buffering and receptor trafficking to muscle cell fusion and metabolic regulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Adilson Guilherme, Neil A Soriano, Sahana Bose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the actin cytoskeleton."}]}, {"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.M307702200"}], "href": "https://doi.org/10.1074/jbc.M307702200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14676205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14676205"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miriam Stoeber, Ina Karen Stoeck, Christine Hänni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oligomers of the ATPase EHD2 confine caveolae to the plasma membrane through association with actin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2012.98"}], "href": "https://doi.org/10.1038/emboj.2012.98"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22505029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22505029"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Maria Hoernke, Jagan Mohan, Elin Larsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1614066114"}], "href": "https://doi.org/10.1073/pnas.1614066114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28223496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28223496"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura C Simone, Steve Caplan, Naava Naslavsky "}, {"type": "b", "children": [{"type": "t", "text": "Role of phosphatidylinositol 4,5-bisphosphate in regulating EHD2 plasma membrane localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0074519"}], "href": "https://doi.org/10.1371/journal.pone.0074519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24040268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24040268"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sigi Benjamin, Hilla Weidberg, Debora Rapaport, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20111010"}], "href": "https://doi.org/10.1042/BJ20111010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21756249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21756249"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Katherine R Doherty, Alexis R Demonbreun, Gregory Q Wallace, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The endocytic recycling protein EHD2 interacts with myoferlin to regulate myoblast fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802306200"}], "href": "https://doi.org/10.1074/jbc.M802306200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18502764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18502764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Claudia Matthaeus, Ines Lahmann, Séverine Kunz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1918415117"}], "href": "https://doi.org/10.1073/pnas.1918415117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32170013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32170013"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Björn Morén, Björn Hansson, Florentina Negoita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E18-10-0680"}], "href": "https://doi.org/10.1091/mbc.E18-10-0680"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30811273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30811273"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mei Li, Xiaojing Yang, Jianguo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of EHD2 interference on migration of esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-012-0396-4"}], "href": "https://doi.org/10.1007/s12032-012-0396-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23354948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23354948"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiaojing Yang, Hanru Ren, Li Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of EHD2 in migration and invasion of human breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-014-3011-9"}], "href": "https://doi.org/10.1007/s13277-014-3011-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25557791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25557791"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yuhua Shi, Xiaobing Liu, Yongfang Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression and prognostic role of EHD2 in human breast carcinoma: correlation with E-cadherin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Histol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10735-015-9614-7"}], "href": "https://doi.org/10.1007/s10735-015-9614-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25758127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25758127"}]}]}]}
Synonyms	PAST2
Proteins	EHD2_HUMAN
NCBI Gene ID	30846
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EHD2 has 6,911 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 119 datasets.

Click the + buttons to view associations for EHD2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 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 EHD2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EHD2 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 EHD2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EHD2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EHD2 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 EHD2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EHD2 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 EHD2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EHD2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EHD2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EHD2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EHD2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EHD2 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 EHD2 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 EHD2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EHD2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EHD2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EHD2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EHD2 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 EHD2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EHD2 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 EHD2 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 EHD2 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 EHD2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EHD2 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 EHD2 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 EHD2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EHD2 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 EHD2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of EHD2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with EHD2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.