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 c... See more...

Aliases for EML4 Gene

Aliases for EML4 Gene

  • EMAP Like 4 2 3 5
  • Restrictedly Overexpressed Proliferation-Associated Protein 3 4
  • Echinoderm Microtubule Associated Protein Like 4 2 3
  • Echinoderm Microtubule-Associated Protein-Like 4 3 4
  • Ropp 120 3 4
  • ROPP120 2 3
  • C2orf2 3 4
  • ELP120 2 3
  • EMAP-4 3 4
  • EMAPL4 3 4
  • EML4 5

External Ids for EML4 Gene

Previous HGNC Symbols for EML4 Gene

  • C2orf2

Previous GeneCards Identifiers for EML4 Gene

  • GC02P042385
  • GC02P042565
  • GC02P042371
  • GC02P042308
  • GC02P042131
  • GC02P042397

Summaries for EML4 Gene

Entrez Gene Summary for EML4 Gene

  • 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]

GeneCards Summary for EML4 Gene

EML4 (EMAP Like 4) is a Protein Coding gene. Diseases associated with EML4 include Signet Ring Lung Adenocarcinoma and Inflammatory Myofibroblastic Tumor. Among its related pathways are Cytoskeletal Signaling and Crizotinib Pathway, Pharmacokinetics/Pharmacodynamics. An important paralog of this gene is EML1.

UniProtKB/Swiss-Prot Summary for EML4 Gene

  • Essential for the formation and stability of microtubules (MTs) (PubMed:16890222, PubMed:31409757). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (PubMed:25789526). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (PubMed:25789526).

Gene Wiki entry for EML4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EML4 Gene

Genomics for EML4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for EML4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J042168 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 268 +1.8 1849 5.2 SP1 ZNF207 ZNF600 ZNF592 ZMYM3 POLR2A ZNF10 YY1 MXD4 REST EML4 EML4-AS1 COX7A2L lnc-PKDCC-4
GH02J042167 Enhancer 0.5 Ensembl 255.1 -1.7 -1652 0.6 TEAD3 USF2 RAD51 TOE1 PRDM10 USF1 CREB1 EML4 EML4-AS1 HSALNG0014464 PKDCC
GH02J042123 Enhancer 1.7 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 67.8 -37.8 -37818 16.7 BCLAF1 SP1 ZNF207 MYC ZNF600 SSRP1 JUND ZNF580 ZMYM3 ATF2 lnc-C2orf91-10 EML4 EML4-AS1 COX7A2L OXER1 HAAO HSALNG0014461 lnc-EML4-2 PKDCC
GH02J042169 Promoter 0.3 Ensembl 250.7 -0.9 -852 0.2 EML4 EML4-AS1 HSALNG0014464 PKDCC
GH02J042100 Enhancer 1.6 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 35.7 -64.1 -64140 9.2 BCLAF1 SP1 ZNF207 ZMYM3 ATF2 KLF9 CEBPA ATF3 POLR2A YY1 EML4 PKDCC EML4-AS1 COX7A2L HSALNG0014457 lnc-C2orf91-4 lnc-PKDCC-9
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EML4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EML4

Top Transcription factor binding sites by QIAGEN in the EML4 gene promoter:
  • AREB6
  • CUTL1
  • GATA-6
  • HNF-1
  • HNF-1A
  • Nkx5-1
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT3
  • YY1

Genomic Locations for EML4 Gene

Latest Assembly
chr2:42,169,353-42,332,548
(GRCh38/hg38)
Size:
163,196 bases
Orientation:
Plus strand

Previous Assembly
chr2:42,396,493-42,559,688
(GRCh37/hg19 by Entrez Gene)
Size:
163,196 bases
Orientation:
Plus strand

chr2:42,396,490-42,559,688
(GRCh37/hg19 by Ensembl)
Size:
163,199 bases
Orientation:
Plus strand

Genomic View for EML4 Gene

Genes around EML4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EML4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EML4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EML4 Gene

Proteins for EML4 Gene

  • Protein details for EML4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HC35-EMAL4_HUMAN
    Recommended name:
    Echinoderm microtubule-associated protein-like 4
    Protein Accession:
    Q9HC35
    Secondary Accessions:
    • A6H8Y6
    • B2RBK3
    • B2RTW7
    • B5MCW9
    • Q3SWW0
    • Q53R29
    • Q53TW8
    • Q6PJ45
    • Q9NV40

    Protein attributes for EML4 Gene

    Size:
    981 amino acids
    Molecular mass:
    108916 Da
    Quaternary structure:
    • Interacts (via WD repeats) with NUDC (PubMed:25789526). Interacts with alpha- and beta-tubulin during mitosis (PubMed:31409757).
    SequenceCaution:
    • Sequence=AAI04648.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAA91919.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for EML4 Gene

    Alternative splice isoforms for EML4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EML4 Gene

Post-translational modifications for EML4 Gene

  • Phosphorylated during mitosis (PubMed:16890222). Phosphorylation at Ser-144 and Ser-146 promotes its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibodies for research

  • Abcam antibodies for EML4
  • Boster Bio Antibodies for EML4
  • Santa Cruz Biotechnology (SCBT) Antibodies for EML4

No data available for DME Specific Peptides for EML4 Gene

Domains & Families for EML4 Gene

Gene Families for EML4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for EML4 Gene

Suggested Antigen Peptide Sequences for EML4 Gene

GenScript: Design optimal peptide antigens:
  • EML4 protein (A6H8Y6_HUMAN)
  • Ropp 120 (EMAL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HC35

UniProtKB/Swiss-Prot:

EMAL4_HUMAN :
  • Belongs to the WD repeat EMAP family.
Family:
  • Belongs to the WD repeat EMAP family.
genes like me logo Genes that share domains with EML4: view

Function for EML4 Gene

Molecular function for EML4 Gene

UniProtKB/Swiss-Prot Function:
Essential for the formation and stability of microtubules (MTs) (PubMed:16890222, PubMed:31409757). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (PubMed:25789526). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (PubMed:25789526).

Phenotypes From GWAS Catalog for EML4 Gene

Gene Ontology (GO) - Molecular Function for EML4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005515 protein binding IEA,IPI 25789526
GO:0008017 microtubule binding IBA 21873635
GO:0043014 alpha-tubulin binding IDA 31409757
GO:0048487 beta-tubulin binding IDA 31409757
genes like me logo Genes that share ontologies with EML4: view
genes like me logo Genes that share phenotypes with EML4: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EML4

Clone products for research

  • Addgene plasmids for EML4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for EML4 Gene

Localization for EML4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EML4 Gene

Cytoplasm, cytoskeleton. Cytoplasm. Cytoplasm, cytoskeleton, spindle. Cytoplasm, cytoskeleton, microtubule organizing center. Midbody. Note=Localizes to microtubules (MTs) during interphase with a significantly reduced affinity for MTs during mitosis. {ECO:0000269 PubMed:31409757}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EML4 gene
Compartment Confidence
cytoskeleton 4
plasma membrane 3
nucleus 3
cytosol 3
extracellular 2
mitochondrion 2
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubules (3)
  • Cytosol (2)
  • Intermediate filaments (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for EML4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm NAS 10995578
GO:0005815 microtubule organizing center IDA 16890222
GO:0005856 cytoskeleton IEA --
GO:0005874 microtubule IEA,IDA 16890222
GO:0016020 membrane HDA 19946888
genes like me logo Genes that share ontologies with EML4: view

Pathways & Interactions for EML4 Gene

genes like me logo Genes that share pathways with EML4: view

Pathways by source for EML4 Gene

1 Cell Signaling Technology pathway for EML4 Gene

Gene Ontology (GO) - Biological Process for EML4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000226 microtubule cytoskeleton organization IBA 21873635
GO:0000278 mitotic cell cycle NAS 10995578
GO:0007017 microtubule-based process NAS 10995578
GO:0007080 mitotic metaphase plate congression IMP 25789526
GO:0008608 attachment of spindle microtubules to kinetochore IMP 25789526
genes like me logo Genes that share ontologies with EML4: view

No data available for SIGNOR curated interactions for EML4 Gene

Drugs & Compounds for EML4 Gene

No Compound Related Data Available

Transcripts for EML4 Gene

mRNA/cDNA for EML4 Gene

2 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EML4

Clone products for research

  • Addgene plasmids for EML4

Alternative Splicing Database (ASD) splice patterns (SP) for EML4 Gene

No ASD Table

Relevant External Links for EML4 Gene

GeneLoc Exon Structure for
EML4

Expression for EML4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EML4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Spleen (Hematopoietic System)
  • Tonsil (Hematopoietic System)

Protein differential expression in normal tissues from HIPED for EML4 Gene

This gene is overexpressed in Lymph node (16.5) and Peripheral blood mononuclear cells (8.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EML4 Gene



Protein tissue co-expression partners for EML4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EML4

SOURCE GeneReport for Unigene cluster for EML4 Gene:

Hs.713173

Evidence on tissue expression from TISSUES for EML4 Gene

  • Nervous system(4.7)
  • Liver(4.6)
  • Lung(3.2)
  • Intestine(2.9)
  • Lymph node(2.8)
  • Skin(2.7)
  • Kidney(2.5)
  • Blood(2.4)
  • Thyroid gland(2.4)
  • Bone marrow(2.3)
  • Heart(2.3)
  • Pancreas(2.3)
  • Spleen(2.2)
  • Adrenal gland(2.2)
  • Stomach(2.1)
genes like me logo Genes that share expression patterns with EML4: view

Primer products for research

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for EML4 Gene

Orthologs for EML4 Gene

This gene was present in the common ancestor of animals.

Orthologs for EML4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia EML4 29 30
  • 97.9 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia EML4 29 30
  • 92.73 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia EML4 29 30
  • 92.65 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Eml4 29 16 30
  • 88 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Eml4 29
  • 87.32 (n)
Oppossum
(Monodelphis domestica)
Mammalia EML4 30
  • 85 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 75 (a)
OneToMany
-- 30
  • 54 (a)
OneToMany
Chicken
(Gallus gallus)
Aves EML4 29 30
  • 80.74 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia EML4 30
  • 76 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia eml4 29
  • 74.05 (n)
Str.7603 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.14971 29
Zebrafish
(Danio rerio)
Actinopterygii EML4 (2 of 2) 30
  • 72 (a)
OneToMany
EML4 (1 of 2) 30
  • 63 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta CG13466 31
  • 34 (a)
DCX-EMAP 30
  • 24 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea elp-1 30 31
  • 24 (a)
OneToMany
Species where no ortholog for EML4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for EML4 Gene

ENSEMBL:
Gene Tree for EML4 (if available)
TreeFam:
Gene Tree for EML4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EML4: view image
Alliance of Genome Resources:
Additional Orthologs for EML4

Paralogs for EML4 Gene

Paralogs for EML4 Gene

(8) SIMAP similar genes for EML4 Gene using alignment to 4 proteins:

  • EMAL4_HUMAN
  • B5MBZ0_HUMAN
  • F2Z2B5_HUMAN
  • Q583U9_HUMAN
genes like me logo Genes that share paralogs with EML4: view

Variants for EML4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EML4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs186464897 Benign: not provided 42,325,463(+) C/G
NM_019063.5(EML4):c.2155-4C>G
INTRON
rs72972015 Benign: not provided 42,280,908(+) C/T
NM_019063.5(EML4):c.726C>T (p.Ser242=)
SYNONYMOUS
rs73933519 Benign: not provided 42,263,316(+) G/A
NM_019063.5(EML4):c.641+10G>A
INTRON
rs10202624 -- p.Ile382Val
rs28364731 -- p.Ser978Leu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for EML4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for EML4 Gene

Variant ID Type Subtype PubMed ID
dgv1117e212 CNV loss 25503493
dgv6825n54 CNV loss 21841781
dgv6826n54 CNV loss 21841781
esv2533393 CNV deletion 19546169
esv2763299 CNV gain+loss 21179565
esv3555555 CNV deletion 23714750
esv3583755 CNV loss 25503493
esv3583756 CNV loss 25503493
esv3590499 CNV loss 21293372
esv3590500 CNV loss 21293372
esv3590501 CNV loss 21293372
esv3891982 CNV loss 25118596
esv8006 CNV gain 19470904
nsv1005165 CNV loss 25217958
nsv2705 CNV insertion 18451855
nsv2706 CNV deletion 18451855
nsv441755 CNV loss 18776908
nsv521335 CNV gain 19592680
nsv525133 CNV gain 19592680
nsv581635 CNV loss 21841781
nsv581640 CNV loss 21841781
nsv581642 CNV loss 21841781

Variation tolerance for EML4 Gene

Residual Variation Intolerance Score: 19.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.17; 87.91% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EML4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
EML4
Leiden Open Variation Database (LOVD)
EML4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EML4 Gene

Disorders for EML4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for EML4 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
signet ring lung adenocarcinoma
inflammatory myofibroblastic tumor
  • inflammatory fibrosarcoma
lung cancer
  • lung cancer, susceptibility to
lung sarcomatoid carcinoma
  • pulmonary sarcomatoid carcinoma
lung non-squamous non-small cell carcinoma
  • non- squamous nsclc
- elite association - COSMIC cancer census association via MalaCards
Search EML4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for EML4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with EML4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EML4 Gene

Publications for EML4 Gene

  1. Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. (PMID: 31409757) Adib R … Fry AM (Science signaling 2019) 3 4
  2. EML4 promotes the loading of NUDC to the spindle for mitotic progression. (PMID: 25789526) Chen D … Senga T (Cell cycle (Georgetown, Tex.) 2015) 3 4
  3. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. (PMID: 20183914) Takahashi T … Date H (Annals of surgical oncology 2010) 3 22
  4. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. (PMID: 20624322) Zhang X … Wu YL (Molecular cancer 2010) 3 40
  5. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. (PMID: 18166835) Inamura K … Ishikawa Y (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2008) 3 22

Products for EML4 Gene

Sources for EML4 Gene