NEBL Gene

Name	nebulette
Description	This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNEBL, a cardiac‐specific isoform of the nebulin family, plays a pivotal role in organizing and maintaining the structural integrity of myofibrils. Functional analyses using GFP‐tagged nebulette constructs have demonstrated that full‐length NEBL integrates into the sarcomere where it colocalizes with alpha‐actinin at the Z‐line, ensuring proper thin filament assembly and contractile performance. Specific domains within NEBL, including its SH3 and nebulin repeat regions, mediate interactions with key cytoskeletal and focal adhesion proteins—such as zyxin, filamin‐C, and Xin—that are critical for both the initiation and maturation of myofibrillogenesis and for stabilizing thin filament components like tropomyosin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic alterations in the NEBL gene have been implicated in pathological conditions affecting the heart and hematopoietic system. Specific NEBL sequence variants have been found in patients with dilated cardiomyopathy and endocardial fibroelastosis, underscoring its fundamental role in cardiac structure and function. In addition, formation of reciprocal fusion genes involving NEBL and the MLL gene in infant acute myeloid leukemia suggests that dysregulation of NEBL not only impairs cardiac integrity but may also contribute to oncogenic transformation in hematopoietic cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its traditional roles in muscle physiology, emerging evidence indicates that NEBL impacts cancer biology and other disease processes. For instance, elevated NEBL expression in colorectal cancer has been correlated with improved overall survival, highlighting its potential as a prognostic biomarker, while in clear cell renal cell carcinoma, reduced NEBL levels are linked to enhanced tumor aggressiveness and a promotion of epithelial–mesenchymal transition. Moreover, genetic variants in NEBL have been associated with susceptibility to multibacillary leprosy, further reflecting the protein’s diverse functional repertoire in human health and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carole L Moncman, Kuan Wang "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/excr.2001.5423"}], "href": "https://doi.org/10.1006/excr.2001.5423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11822876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11822876"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bo Li, Lei Zhuang, Beat Trueb "}, {"type": "b", "children": [{"type": "t", "text": "Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1."}]}, {"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.M310304200"}], "href": "https://doi.org/10.1074/jbc.M310304200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15004028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15004028"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "William B Holmes, Carole L Moncman "}, {"type": "b", "children": [{"type": "t", "text": "Nebulette interacts with filamin C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Motil Cytoskeleton (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cm.20249"}], "href": "https://doi.org/10.1002/cm.20249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17987659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17987659"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeremy R Bonzo, Andrea A Norris, Michael Esham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2008.09.001"}], "href": "https://doi.org/10.1016/j.yexcr.2008.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18823973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18823973"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Stefan Eulitz, Florian Sauer, Marie-Cecile Pelissier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Xin-repeat proteins as novel ligands of the SH3 domains of nebulin and nebulette and analysis of their interaction during myofibril formation and remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-04-0202"}], "href": "https://doi.org/10.1091/mbc.E13-04-0202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23985323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23985323"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Enkhsaikhan Purevjav, Jaquelin Varela, Micaela Morgado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Coll Cardiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jacc.2010.05.045"}], "href": "https://doi.org/10.1016/j.jacc.2010.05.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20951326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20951326"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mariana Emerenciano, Eric Kowarz, Katharina Karl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of the two reciprocal fusion genes MLL-NEBL and NEBL-MLL reveal their oncogenic potential."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2012.12.023"}], "href": "https://doi.org/10.1016/j.canlet.2012.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23340173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23340173"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Audrey V Grant, Aurelie Cobat, Nguyen Van Thuc, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-014-1430-8"}], "href": "https://doi.org/10.1007/s00439-014-1430-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24563210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24563210"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiao Qiu, Jue-Rong Feng, Fan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2017.8210"}], "href": "https://doi.org/10.3892/mmr.2017.8210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29257257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29257257"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ran Zhao, Ziyuan Liang, Jiemei Chu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2023.155068"}], "href": "https://doi.org/10.1016/j.prp.2023.155068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38215565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38215565"}]}]}]}
Synonyms	LNEBL, LASP2
Proteins	NEBL_HUMAN
NCBI Gene ID	10529
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NEBL has 12,672 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 118 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL 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 NEBL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NEBL protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NEBL 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 NEBL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NEBL 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 NEBL 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 NEBL 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 NEBL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NEBL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NEBL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NEBL 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 NEBL 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 NEBL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NEBL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NEBL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NEBL gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with NEBL 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 NEBL 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 NEBL gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with NEBL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NEBL 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 NEBL 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 NEBL 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 NEBL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NEBL 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 NEBL 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 NEBL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NEBL 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 NEBL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NEBL gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NEBL gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.