EML4 Gene: Echinoderm Microtubule Associated Protein Like 4
A key oncogene in non-small cell lung cancer, frequently involved in ALK gene fusions.
Gene Information Card
| Symbol | EML4 |
|---|---|
| Full Name | Echinoderm Microtubule Associated Protein Like 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p21 |
| NCBI Gene ID | 27436 ncbi.nlm.nih.gov/gene/27436 |
| Ensembl ID | ENSG00000143924 |
| UniProt ID | Q9HC35 |
| OMIM ID | 607442 |
| HGNC ID | 1316 |
| Aliases | ELP120, ROPP120, C2orf2 |
Description
The EML4 gene encodes a protein that belongs to the echinoderm microtubule-associated protein (EMAP) family. It is involved in microtubule dynamics and plays a role in cell division and intracellular transport. EML4 is widely known for its recurrent chromosomal rearrangements with the ALK gene, creating the EML4-ALK fusion oncogene, which is a major driver in a subset of non-small cell lung cancers (NSCLC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Non-small cell lung cancer (NSCLC) | Chromosomal inversion on chromosome 2p results in EML4-ALK fusion, leading to constitutive ALK kinase activation and oncogenic signaling. | COSMIC, ClinVar, multiple studies |
| Inflammatory myofibroblastic tumor | EML4-ALK fusion has also been detected in this rare soft tissue tumor, contributing to ALK activation. | Case reports, ClinVar |
| Colorectal cancer | Rare EML4-ALK fusions have been identified, suggesting a potential role in a subset of colorectal cancers. | COSMIC, case studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Lung | 8.5 | Low |
| Testis | 7.8 | Low |
| Kidney | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 12.5 | Moderate expression |
| HeLa (Cervical carcinoma) | 15.3 | High expression |
| MCF7 (Breast carcinoma) | 9.8 | Low expression |
| HepG2 (Liver carcinoma) | 11.2 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| EML4-ALK fusion (variant 1) | Chromosomal inversion | ~3-7% of NSCLC | Constitutive ALK activation, oncogenic transformation |
| EML4-ALK fusion (variant 3a/b) | Chromosomal inversion | ~1-2% of NSCLC | Constitutive ALK activation, oncogenic transformation |
| Missense mutations (e.g., R558W) | Point mutation | Rare (<0.1%) | Unknown; may affect microtubule binding |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in EML4 are rare and not well characterized; they may impair microtubule dynamics but are not known to drive cancer.
Gain of Function (GOF)
The EML4-ALK fusion is a classic gain-of-function mutation, resulting in a chimeric protein with constitutive ALK kinase activity, driving cell proliferation and survival.
Dominant Negative (DN)
No dominant-negative effects have been reported for EML4 mutations.
View complete mutation data：
Gene Ontology (GO)
| • microtubule binding | • microtubule cytoskeleton organization |
| • cell division | • intracellular transport |
| • protein homodimerization activity |
Pathways
• ALK signaling pathway
• MAPK/ERK pathway
• PI3K/AKT pathway
• JAK/STAT pathway
Protein Summary
The EML4 protein is a 120 kDa cytoplasmic protein that associates with microtubules and regulates their stability and dynamics. It contains an N-terminal echinoderm microtubule-associated protein (EMAP) domain and a C-terminal WD40 repeat domain. In cancer, the EML4-ALK fusion protein retains the N-terminal coiled-coil domain of EML4, which mediates dimerization and constitutive activation of the ALK kinase domain, leading to oncogenic signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EML4 Knockout HEK293 Cell Line | EDJ-KQ3133 | Human | 27436 | Details Get a Quote |
| EML4 Knockout HeLa Cell Line | EDJ-KQ23124 | Human | 27436 | Details Get a Quote |
| EML4 Knockout A-549 Cell Line | EDJ-KQ24507 | Human | 27436 | Details Get a Quote |
| EML4 Knockout HCT 116 Cell Line | EDJ-KQ24508 | Human | 27436 | Details Get a Quote |
| EML4 (c.1011+60A>G )Point Mutation in HAP1 Cell Line | EDC03454 | Human | 27436 | Details Get a Quote |
