MECOM (MDS1 and EVI1 Complex Locus)
A key transcriptional regulator in hematopoiesis and oncogenesis
Gene Information Card
| Symbol | MECOM |
|---|---|
| Full Name | MDS1 and EVI1 complex locus |
| Gene Type | Protein coding |
| Chromosomal Location | 3q26.2 |
| NCBI Gene ID | 2122 ncbi.nlm.nih.gov/gene/2122 |
| Ensembl ID | ENSG00000185276 |
| UniProt ID | Q03112 |
| OMIM ID | 165215 |
| HGNC ID | 3498 |
| Aliases | EVI1, MDS1, PRDM3, AML1-EVI1, MECOM |
Description
MECOM (MDS1 and EVI1 complex locus) encodes a zinc finger transcription factor that plays a critical role in hematopoiesis, cell proliferation, and differentiation. The gene produces multiple isoforms through alternative splicing, including the EVI1 and MDS1-EVI1 proteins. MECOM is frequently activated by chromosomal rearrangements involving 3q26, leading to overexpression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It functions as an oncogene by repressing tumor suppressor genes and promoting self-renewal of hematopoietic stem cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia (AML) | 3q26 rearrangements (e.g., inv(3)(q21q26), t(3;3)(q21;q26)) cause MECOM overexpression, disrupting hematopoietic differentiation and promoting leukemogenesis. | ClinVar, COSMIC, OMIM |
| Myelodysplastic syndromes (MDS) | Similar 3q26 rearrangements lead to MECOM activation, associated with poor prognosis and progression to AML. | ClinVar, COSMIC, OMIM |
| Chronic myeloid leukemia (CML) | MECOM overexpression via t(3;21)(q26;q22) fusion with RUNX1 contributes to blast crisis. | COSMIC, NCBI |
| Breast cancer | MECOM overexpression correlates with poor prognosis and promotes epithelial-mesenchymal transition. | COSMIC, NCBI |
| Ovarian cancer | MECOM amplification and overexpression linked to aggressive tumor behavior. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Low |
| Thymus | 6.1 | Low |
| Kidney | 4.2 | Low |
| Lung | 3.8 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | 15.2 | High expression; used as model for MECOM studies |
| HEL (erythroleukemia) | 14.8 | High expression |
| MOLM-13 (AML) | 12.1 | High expression |
| HL-60 (promyelocytic leukemia) | 9.5 | Moderate expression |
| HEK293 (embryonic kidney) | 2.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| 3q26 rearrangements (inv(3), t(3;3)) | Structural variant | Common in AML/MDS | Leads to MECOM overexpression and leukemogenesis |
| t(3;21)(q26;q22) | Fusion (RUNX1-MECOM) | Rare in CML blast crisis | Chimeric protein with altered transcriptional activity |
| Amplification | Copy number gain | Observed in solid tumors (breast, ovarian) | Increased MECOM dosage promotes oncogenesis |
| Missense mutations (e.g., R205Q) | Point mutation | Rare | Potential loss of DNA-binding affinity |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations in the zinc finger domains may impair DNA binding and transcriptional repression, but LOF is not a common mechanism in MECOM-associated diseases.
Gain of Function (GOF)
Chromosomal rearrangements (inv(3), t(3;3)) and amplifications result in MECOM overexpression, acting as a gain-of-function oncogenic driver in myeloid malignancies and solid tumors.
Dominant Negative (DN)
Fusion proteins such as RUNX1-MECOM may exhibit dominant-negative effects by interfering with wild-type RUNX1 function, contributing to leukemogenesis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hematopoietic stem cell self-renewal (MECOM overexpression)
• TGF-beta signaling pathway (MECOM represses TGFB1)
• JAK-STAT signaling pathway (MECOM interacts with JAK2)
• p53 signaling pathway (MECOM represses TP53)
• Wnt signaling pathway (MECOM modulates beta-catenin)
Protein Summary
The MECOM protein (EVI1) is a 1051-amino acid nuclear transcription factor containing two sets of zinc finger domains (N-terminal and C-terminal) and a proline-rich region. It binds to DNA at consensus sequences (GATA-like motifs) and regulates gene expression by recruiting co-repressors (e.g., CtBP, HDACs) or co-activators. EVI1 represses tumor suppressor genes such as TGFB1, PTEN, and TP53, while promoting self-renewal genes like GATA2. The MDS1-EVI1 isoform includes an additional PR domain with methyltransferase activity. Overexpression of MECOM blocks hematopoietic differentiation and confers a proliferative advantage in leukemia and solid tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MECOM Knockout HEK293 Cell Line | EDJ-KQ711 | Human | 2122 | Details Get a Quote |
| MECOM Knockout HCT 116 Cell Line | EDJ-KQ19308 | Human | 2122 | Details Get a Quote |
| MECOM Knockout HeLa Cell Line | EDJ-KQ19309 | Human | 2122 | Details Get a Quote |
| MECOM Knockout A-549 Cell Line | EDJ-KQ61659 | Human | 2122 | Details Get a Quote |
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