ESPN Gene

HGNC Family	Ankyrin repeat domain containing (ANKRD)
Name	espin
Description	This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nEspin, encoded by the ESPN gene, is a calcium‐insensitive actin‐bundling protein that plays an essential role in the function of inner ear hair cells. Mutations in ESPN, including frameshift events, have been identified in humans with autosomal recessive deafness and vestibular areflexia, mirroring similar defects observed in the jerker mouse. These findings underscore espin’s critical role in stereocilia development and function, making it a key determinant in hearing and balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, espin promotes the assembly and elongation of parallel actin bundles in stereocilia and microvilli. Beyond its classic actin‐bundling activity, espin possesses a unique function mediated by its WH2 domain, which enables the targeted assembly of large actin bundles at specific subcellular locales. This novel activity highlights the versatility of espin in remodeling the actin cytoskeleton."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEspin’s function is further regulated through its interactions with partner proteins. In hair cells, class III myosins (Myo3) interact with espin isoforms, where binding via specific repeat sequences leads to a cross‐linking mechanism and the alleviation of auto-inhibition, thereby enhancing espin’s actin-bundling capability. Moreover, regulation of additional actin-binding sites in large espin isoforms, through interactions involving ankyrin repeat domains and myosin III tail homology regions, further refines actin bundle assembly and stability in stereocilia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established role in the auditory system, espin has emerged as a significant factor in other biological contexts. In damaged vestibular sensory epithelia, gene therapy with espin1 has been demonstrated to promote the regeneration of immature stereociliary bundles, a promising strategy for restoring hair cell function. In parallel, espin has been identified as a direct target of miR-612 in melanoma cells, where its downregulation is associated with reduced proliferation, invasion, and tumorigenesis, highlighting its influence in oncogenic processes. Additionally, investigations using Drosophila models have contributed valuable insights into the conserved molecular mechanisms underlying hearing loss, and studies on protein complexes implicated in Usher syndrome further support espin’s contribution to the pathology of combined sensory deficits."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Naz, A J Griffith, S Riazuddin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2004.018523"}], "href": "https://doi.org/10.1136/jmg.2004.018523"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15286153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15286153"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Donaudy, L Zheng, R Ficarella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2005.032086"}], "href": "https://doi.org/10.1136/jmg.2005.032086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15930085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15930085"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Patricia A Loomis, Alexander E Kelly, Lili Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02869"}], "href": "https://doi.org/10.1242/jcs.02869"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16569662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16569662"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lili Zheng, Dina M Beeler, James R Bartles "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and regulation of an additional actin-filament-binding site in large isoforms of the stereocilia actin-bundling protein espin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.143255"}], "href": "https://doi.org/10.1242/jcs.143255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24424026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24424026"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haiyang Liu, Jianchao Li, Manmeet H Raval, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.12856"}], "href": "https://doi.org/10.7554/eLife.12856"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26785147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26785147"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Maura Cosetti, David Culang, Sumankrishna Kotla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unique transgenic animal model for hereditary hearing loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Otol Rhinol Laryngol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/000348940811701106"}], "href": "https://doi.org/10.1177/000348940811701106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19102128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19102128"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A Taura, K Taura, Y Koyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Ther (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gt.2016.12"}], "href": "https://doi.org/10.1038/gt.2016.12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26886463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26886463"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ying Zhu, Hao-Liang Zhang, Qi-Ying Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2018.2235"}], "href": "https://doi.org/10.14348/molcells.2018.2235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29385671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29385671"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zubair M Ahmed, Thomas J Jaworek, Gowri N Sarangdhar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inframe deletion of human "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ESPN"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " is associated with deafness, vestibulopathy and vision impairment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2017-105221"}], "href": "https://doi.org/10.1136/jmedgenet-2017-105221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29572253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29572253"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Le Wang, Bo Wei, Xueqi Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of whirlin domains interacting with espin: A study of the mechanism of Usher syndrome type II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2019.10728"}], "href": "https://doi.org/10.3892/mmr.2019.10728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31638198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31638198"}]}]}]}
Synonyms	DFNB36, LP2654
Proteins	ESPN_HUMAN
NCBI Gene ID	83715
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ESPN has 5,446 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 111 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

ESPN 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 ESPN gene relative to other tissues from the Allen Brain Atlas Adult Human 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 ESPN 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 ESPN 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 ESPN 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 ESPN 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 ESPN 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 ESPN 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 ESPN 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 ESPN 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 ESPN gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ESPN protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ESPN 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 ESPN gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ESPN 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 ESPN 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 ESPN gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ESPN 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 ESPN gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ESPN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ESPN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ESPN 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 ESPN 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 ESPN 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 ESPN gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ESPN gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ESPN gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ESPN gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ESPN 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 ESPN gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ESPN gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ESPN gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ESPN 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 ESPN 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 ESPN gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ESPN 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 ESPN 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 ESPN gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ESPN 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 ESPN from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ESPN gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.