METTL14 Gene: Methyltransferase 14, N6-Methyladenosine-Methyltransferase Subunit
METTL14 is a core component of the m6A RNA methyltransferase complex, playing a critical role in RNA metabolism, gene expression regulation, and cancer biology.
Gene Information Card
| Symbol | METTL14 |
|---|---|
| Full Name | Methyltransferase 14, N6-Methyladenosine-Methyltransferase Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 4q26 |
| NCBI Gene ID | 57721 ncbi.nlm.nih.gov/gene/57721 |
| Ensembl ID | ENSG00000145362 |
| UniProt ID | Q9HCE5 |
| OMIM ID | 615322 |
| HGNC ID | 29330 |
| Aliases | Methyltransferase Like 14, KIAA1622, METTL14 (m6A methyltransferase subunit) |
Description
METTL14 (Methyltransferase 14, N6-Methyladenosine-Methyltransferase Subunit) encodes a key component of the N6-methyladenosine (m6A) RNA methyltransferase complex. This complex, which also includes METTL3 and other regulatory proteins, catalyzes the addition of a methyl group to the N6 position of adenosine in mRNA and other nuclear RNAs. METTL14 is essential for the structural integrity and catalytic activity of the complex, primarily by recognizing and binding RNA substrates. Through m6A modification, METTL14 regulates various aspects of RNA metabolism, including mRNA stability, splicing, export, and translation. It plays a critical role in numerous biological processes such as cell differentiation, embryonic development, and DNA damage response. Dysregulation of METTL14 has been implicated in various cancers and other diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Reduced METTL14 expression leads to decreased m6A methylation on specific target mRNAs, promoting self-renewal of leukemia stem cells and blocking differentiation. | Multiple studies show METTL14 is downregulated in AML and acts as a tumor suppressor (e.g., Weng et al., 2018). |
| Hepatocellular Carcinoma (HCC) | METTL14 suppresses HCC metastasis by modulating m6A methylation of primary microRNAs (pri-miRNAs), affecting their processing and downstream target gene expression. | Studies demonstrate that METTL14 expression is downregulated in HCC and correlates with poor prognosis (e.g., Ma et al., 2017). |
| Colorectal Cancer (CRC) | METTL14 functions as a tumor suppressor by regulating m6A modification of key oncogenes or tumor suppressors, impacting cell proliferation, invasion, and apoptosis. | Research indicates that METTL14 is downregulated in CRC tissues and its low expression is associated with worse patient outcomes (e.g., Yang et al., 2020). |
| Glioblastoma (GBM) | METTL14 promotes tumorigenesis in GBM by increasing m6A methylation of certain oncogenic transcripts, enhancing their stability and expression. | Studies show METTL14 is overexpressed in GBM and contributes to cancer cell growth and invasion (e.g., Cui et al., 2017). |
| Diabetic Nephropathy | METTL14-mediated m6A modification is involved in high glucose-induced podocyte injury and renal fibrosis, contributing to the progression of diabetic nephropathy. | Research suggests that METTL14 expression is altered in kidney tissues under diabetic conditions, affecting cellular signaling pathways (e.g., Li et al., 2021). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 24.5 | High |
| Kidney | 18.2 | Medium |
| Liver | 15.1 | Medium |
| Lung | 12.8 | Medium |
| Brain | 10.5 | Medium |
| Heart | 8.9 | Low |
| Skeletal Muscle | 6.3 | Low |
| Pancreas | 5.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Hep G2 (Liver) | 20.1 | High expression, consistent with liver tissue data. |
| A-549 (Lung) | 15.4 | Moderate expression. |
| K-562 (Bone Marrow) | 12.3 | Moderate expression, relevant to leukemia studies. |
| MCF7 (Breast) | 9.8 | Low to moderate expression. |
| HeLa (Cervix) | 8.5 | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1169A>G (p.Asp390Gly) | Missense | Rare (<0.01%) | Predicted to be damaging; may affect protein stability or interaction with METTL3. |
| c.157C>T (p.Arg53Trp) | Missense | Rare (<0.01%) | Located in the MT-A70 domain; potentially affects catalytic activity. |
| c.1045C>T (p.Arg349Ter) | Nonsense | Very rare | Introduces a premature stop codon, likely leading to nonsense-mediated decay and loss of function. |
| c.1123_1124insA (p.Leu375fs) | Frameshift | Very rare | Causes a frameshift and premature termination, resulting in a truncated non-functional protein. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in METTL14, such as nonsense, frameshift, or damaging missense variants, reduce or abolish the m6A methyltransferase activity of the METTL3/METTL14 complex. This leads to global or transcript-specific decreases in m6A methylation, altering the stability and translation of target mRNAs. In many cancers like AML and HCC, this loss of function promotes tumorigenesis by stabilizing oncogenic transcripts or destabilizing tumor suppressor transcripts.
Gain of Function (GOF)
Gain-of-function mutations in METTL14 are less commonly described. However, gene amplification or overexpression of wild-type METTL14 can lead to increased m6A methylation of specific targets, as observed in glioblastoma, where it promotes the stability of oncogenic mRNAs and enhances tumor cell proliferation and invasion.
Dominant Negative (DN)
Given that METTL14 forms a stable heterodimer with METTL3, certain missense mutations in the dimerization interface could exert a dominant-negative effect. Such a mutant METTL14 protein could bind to METTL3 but fail to form a functional catalytic core, thereby reducing the overall m6A methyltransferase activity of the complex in a heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • mRNA N6-methyladenosine methyltransferase activity | • RNA binding |
| • Methyltransferase activity | • Nucleus |
| • Cytoplasm | • mRNA processing |
| • Regulation of gene expression | • RNA modification |
| • mRNA stability regulation | • Cell differentiation |
Pathways
• mRNA m6A methylation pathway
• RNA metabolism
• Epigenetic regulation of gene expression
• Regulation of mRNA stability by proteins that bind AU-rich elements
• Developmental biology
Protein Summary
METTL14 is a 587-amino acid protein that serves as a non-catalytic subunit of the m6A methyltransferase complex. It contains an MT-A70-like domain that is crucial for RNA substrate recognition and binding. METTL14 forms a stable heterodimer with the catalytic subunit METTL3. In this complex, METTL3 provides the catalytic core, while METTL14 is essential for the structural stability of the complex and for recognizing and binding specific RNA sequences, particularly the DRACH motif (D=A/G/U, R=A/G, H=A/C/U). This interaction is critical for the efficient and specific deposition of m6A marks on target mRNAs. Through its role in m6A methylation, METTL14 influences various aspects of RNA fate, including splicing, nuclear export, translation, and stability, thereby playing a central role in post-transcriptional gene regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| METTL14 Knockout HEK293 Cell Line | EDJ-KQ51588 | Human | 57721 | Details Get a Quote |
| METTL14 Knockout HeLa Cell Line | EDJ-KQ56910 | Human | 57721 | Details Get a Quote |
| METTL14 Knockout A-549 Cell Line | EDJ-KQ65420 | Human | 57721 | Details Get a Quote |
| METTL14 Knockout HCT 116 Cell Line | EDJ-KQ73857 | Human | 57721 | Details Get a Quote |
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