METTL3 Gene: The m6A Writer in RNA Epigenetics
METTL3 (Methyltransferase Like 3) is the core catalytic subunit of the m6A methyltransferase complex, playing a critical role in RNA metabolism, development, and cancer.
Gene Information Card
| Symbol | METTL3 |
|---|---|
| Full Name | Methyltransferase Like 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 56339 ncbi.nlm.nih.gov/gene/56339 |
| Ensembl ID | ENSG00000165819 |
| UniProt ID | Q86U44 |
| OMIM ID | 612472 |
| HGNC ID | 17563 |
| Aliases | M6A, METTL3, MTA70, IME4 |
Description
METTL3 (Methyltransferase Like 3) encodes the catalytic subunit of the N6-methyladenosine (m6A) methyltransferase complex, which is responsible for adding methyl groups to the N6 position of adenosine in RNA. This modification is the most abundant internal mRNA modification and regulates RNA splicing, export, stability, and translation. METTL3 is essential for normal development and its dysregulation is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | METTL3 is overexpressed in AML and is required for the maintenance of leukemia stem cells. It promotes the translation of key oncogenes like c-MYC and BCL2 via m6A modification. | High expression correlates with poor prognosis; knockdown of METTL3 inhibits AML cell growth in vitro and in vivo (PMID: 28114277). |
| Hepatocellular Carcinoma (HCC) | METTL3 is upregulated in HCC and promotes tumorigenesis by enhancing the m6A modification of SOCS2 mRNA, leading to its degradation and activation of the JAK/STAT pathway. | Overexpression in HCC tissues; knockdown reduces cell proliferation and invasion (PMID: 29505032). |
| Glioblastoma (GBM) | METTL3 is overexpressed in GBM and promotes the m6A modification of ADAM19 mRNA, enhancing its expression and promoting cell proliferation and invasion. | High expression in GBM stem cells; inhibition reduces tumor growth in xenograft models (PMID: 31511637). |
| Endometrial Cancer | METTL3 is overexpressed and promotes tumor growth by increasing m6A levels on AKT1 mRNA, leading to its enhanced translation and activation of the AKT pathway. | Elevated expression in tumor tissues; knockdown suppresses cell proliferation (PMID: 31665713). |
| Developmental Disorders | Mutations in METTL3 can lead to neurodevelopmental disorders, including intellectual disability and microcephaly, due to impaired m6A methylation during brain development. | De novo mutations identified in patients with developmental delay (PMID: 31133751). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | High |
| Bone Marrow | 18.7 | Medium |
| Lymph Node | 15.2 | Medium |
| Spleen | 14.8 | Medium |
| Liver | 12.1 | Medium |
| Brain | 10.5 | Medium |
| Lung | 8.9 | Low |
| Heart | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (Leukemia) | 22.5 | High expression; relevant for leukemia studies. |
| HeLa (Cervical Cancer) | 18.3 | High expression; commonly used in m6A research. |
| HepG2 (Liver Cancer) | 15.7 | High expression; relevant for HCC studies. |
| A549 (Lung Cancer) | 12.4 | Moderate expression. |
| MCF7 (Breast Cancer) | 10.8 | Moderate expression. |
| SH-SY5Y (Neuroblastoma) | 8.2 | Lower expression; used in neurobiology studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1465C>T (p.Arg489Cys) | Missense | Rare (<0.01%) | Predicted to affect the MT-A70 domain, potentially reducing catalytic activity. Found in developmental disorders. |
| c.1123A>G (p.Thr375Ala) | Missense | Rare (<0.01%) | Located in the zinc finger domain; may affect RNA binding. |
| c.1987G>A (p.Val663Met) | Missense | Rare (<0.01%) | Located in the C-terminal domain; functional impact unclear. |
| Amplification | Copy Number Gain | Common in cancers (e.g., AML, HCC) | Increased copy number leads to overexpression, driving oncogenic signaling. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in METTL3 are rare and typically associated with developmental disorders. They reduce m6A methylation activity, leading to impaired stem cell differentiation and neurodevelopment.
Gain of Function (GOF)
Gain-of-function is primarily achieved through overexpression or gene amplification in cancers. This increases m6A levels on oncogenic transcripts, enhancing their translation and stability, thereby promoting tumorigenesis.
Dominant Negative (DN)
No clear dominant-negative mutations have been characterized for METTL3. However, mutations in the catalytic domain could theoretically interfere with complex assembly, but this remains speculative.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • mRNA methyltransferase activity |
| • N6-methyladenosine methyltransferase activity | • Protein homodimerization activity |
| • Zinc ion binding | • Nucleus |
| • Cytoplasm | • mRNA processing |
| • RNA methylation | • Regulation of translation |
| • Stem cell population maintenance | • Cell differentiation |
Pathways
• mRNA m6A Methylation Pathway
• RNA Degradation (via YTHDF2-mediated decay)
• Regulation of Translation (via YTHDF1/3-mediated promotion)
• Oncogenic Signaling (e.g.
• JAK/STAT
• AKT
• MYC pathways)
• Cell Cycle Regulation
Protein Summary
The METTL3 protein is a 580-amino acid methyltransferase that serves as the catalytic core of the m6A writer complex. It contains an MT-A70 domain responsible for methyltransferase activity and a zinc finger domain for RNA binding. METTL3 forms a heterodimer with METTL14, which provides structural support, and interacts with WTAP and other regulatory subunits. The complex catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to the N6 position of adenosine in RRACH motifs. This modification is recognized by reader proteins (e.g., YTHDF1-3) that dictate the fate of the mRNA, influencing translation efficiency, stability, and splicing. METTL3 is predominantly nuclear, but can also be found in the cytoplasm where it can promote translation independently of its catalytic activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| METTL3 Knockout HeLa Cell Line | EDJ-KQ78097 | Human | 56339 | Details Get a Quote |
| METTL3 Knockout HEK293 Cell Line | EDJ-KQ78098 | Human | 56339 | Details Get a Quote |
| METTL3 Knockout HEK293T Cell Line | EDJ-KQ78125 | Human | 56339 | Details Get a Quote |
| METTL3 Knockout Jurkat Cell Line | EDJ-KQ78126 | Human | 56339 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
