EML4 Gene

HGNC Family	WD repeat domain containing (WDR)
Name	echinoderm microtubule associated protein like 4
Description	This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants. [provided by RefSeq, Jan 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Echinoderm microtubule‐associated protein‐like 4 (EML4) is a multifunctional protein normally involved in microtubule stabilization. In a subset of non–small‐cell lung cancers, a paracentric inversion on chromosome 2 leads to the fusion of the N‐terminal portion of EML4 with the intracellular kinase domain of the anaplastic lymphoma kinase (ALK) gene. The resulting EML4–ALK chimeric oncoprotein utilizes structural elements provided by EML4—most notably its coiled‐coil oligomerization domain—to induce ligand‐independent dimerization and constitutive ALK kinase activity. This persistent kinase activation, in turn, drives multiple oncogenic signaling cascades that promote cell proliferation, survival, and transformation, thereby defining a distinct molecular and clinicopathologic subset of lung adenocarcinomas that frequently occur in younger patients and in those with minimal tobacco exposure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to providing a molecular basis for oncogenesis, the EML4 portion of the fusion protein also contributes to the diversity of EML4–ALK variants. Distinct breakpoints within the EML4 gene yield multiple fusion isoforms that may impact the strength and nature of downstream signaling and thus influence both tumor morphology and therapeutic response. Several studies using multiplex reverse transcription–PCR and genomic analyses have identified both previously known and novel EML4–ALK variants with potent transforming activity and differential responses to ALK inhibitors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, clinical screening efforts have demonstrated that the presence of the EML4–ALK fusion is largely mutually exclusive with other oncogenic driver mutations, such as those in EGFR or KRAS, and it portends distinct clinical characteristics and sensitivity to ALK‐targeted therapies. Comprehensive molecular evaluations have further underscored the importance of accurately detecting EML4–ALK fusions for guiding treatment decisions in lung cancer patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the function of EML4 in the context of these malignancies is to serve as a critical molecular scaffold that not only mediates aberrant ALK kinase activation but also influences the biological behavior of the tumor. This dual role makes the EML4–ALK fusion both a key driver of oncogenesis and an actionable target in personalized cancer therapy.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alice T Shaw, Beow Y Yeap, Mari Mino-Kenudson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2009.22.6993"}], "href": "https://doi.org/10.1200/JCO.2009.22.6993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19667264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19667264"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jussi P Koivunen, Craig Mermel, Kreshnik Zejnullahu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-08-0168"}], "href": "https://doi.org/10.1158/1078-0432.CCR-08-0168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18594010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18594010"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kengo Takeuchi, Young Lim Choi, Manabu Soda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-08-1018"}], "href": "https://doi.org/10.1158/1078-0432.CCR-08-1018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18927303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18927303"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kentaro Inamura, Kengo Takeuchi, Yuki Togashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0b013e31815e8b60"}], "href": "https://doi.org/10.1097/JTO.0b013e31815e8b60"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18166835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18166835"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Young Lim Choi, Kengo Takeuchi, Manabu Soda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-6158"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-6158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18593892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18593892"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tsuyoshi Takahashi, Makoto Sonobe, Masashi Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-009-0808-7"}], "href": "https://doi.org/10.1245/s10434-009-0808-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20183914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20183914"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sven Perner, Patrick L Wagner, Francesca Demichelis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EML4-ALK fusion lung cancer: a rare acquired event."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.07878"}], "href": "https://doi.org/10.1593/neo.07878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18320074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18320074"}]}]}]}
Synonyms	EMAPL4, ROPP120, C2ORF2, ELP120, EMAP-4
Proteins	EMAL4_HUMAN
NCBI Gene ID	27436
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EML4 has 7,552 functional associations with biological entities spanning 9 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, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for EML4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EML4 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 EML4 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 EML4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of EML4 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 EML4 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 EML4 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 EML4 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 EML4 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 EML4 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 EML4 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 EML4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with EML4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EML4 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EML4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EML4 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 EML4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EML4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EML4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EML4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EML4 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 EML4 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 EML4 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 EML4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EML4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EML4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EML4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EML4 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 EML4 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 EML4 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 EML4 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 EML4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EML4 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 EML4 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 EML4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EML4 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 EML4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with EML4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with EML4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of EML4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with EML4 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 EML4 from the GeneSigDB Published Gene Signatures dataset.