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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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METTL14
methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit
Chromosome 4 · 4q26
NCBI Gene: 57721Ensembl: ENSG00000145388.16HGNC: HGNC:29330UniProt: Q9HCE5
151PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mRNA m(6)A methyltransferase activityS-adenosyl-L-methionine bindingpositive regulation of translationnegative regulation of hematopoietic progenitor cell differentiationneurodegenerative diseaseliver diseasegeneralized dystoniaclavicle fracture
✦AI Summary

METTL14 is a non-catalytic subunit of the METTL3-METTL14 heterodimer complex that catalyzes N6-methyladenosine (m6A) modifications on mammalian nuclear RNAs 1. Within this complex, METTL14 functions as the RNA-binding scaffold that recognizes substrates at consensus 5'-[AG]GAC-3' sites, while METTL3 provides catalytic activity 1. The m6A modification profoundly influences RNA metabolism, with reader proteins like YTHDFs primarily promoting mRNA degradation through cytoplasmic pathways 2. METTL14 regulates diverse biological processes including embryonic stem cell differentiation, cortical neurogenesis, and spermatogenesis through m6A-mediated mRNA destabilization 1. In disease contexts, METTL14 downregulation associates with colorectal cancer progression and poor survival; mechanistically, reduced METTL14 increases SOX4 mRNA stability via decreased m6A modification, promoting epithelial-mesenchymal transition and metastasis 3. Conversely, elevated METTL14 contributes to vascular aging through enhanced m6A modification of TLR4 mRNA, increasing inflammatory responses 4. Additionally, METTL14-dependent m6A methylation regulates mitochondrial function by promoting translation of nuclear-encoded mitochondrial complex subunits 5. METTL14 emerges as a context-dependent therapeutic target across multiple disease pathologies.

Sources cited
1
METTL3-METTL14 heterodimer catalyzes m6A methylation at 5'-[AG]GAC-3' sites; METTL14 serves as RNA-binding scaffold
PMID: 24316715
2
YTHDF reader proteins promote m6A-containing mRNA degradation; m6A regulation of RNA stability depends on sequence context and cellular environment
PMID: 38629637
3
METTL14 downregulation in colorectal cancer increases SOX4 mRNA stability and promotes metastasis; METTL14 is independent prognostic factor
PMID: 32552762
4
METTL14 upregulation in vascular aging promotes TLR4 mRNA m6A modification and stability, increasing inflammation; METTL14 deletion attenuates arterial stiffness
PMID: 40758401
5
METTL14-dependent m6A methylation regulates mitochondrial function by promoting translation of mitochondrial complex subunit mRNAs
PMID: 38483349
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.55Moderate
liver diseaseOpen Targets
0.19Weak
generalized dystoniaOpen Targets
0.19Weak
clavicle fractureOpen Targets
0.17Weak
shoulder fractureOpen Targets
0.15Weak
colorectal carcinomaOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
gastric cancerOpen Targets
0.11Weak
nonpapillary renal cell carcinomaOpen Targets
0.11Weak
nasopharyngeal carcinomaOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.10Weak
triple-negative breast cancerOpen Targets
0.10Weak
cancerOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.10Suggestive
renal cell carcinomaOpen Targets
0.10Suggestive
osteosarcomaOpen Targets
0.10Suggestive
posterior cortical atrophyOpen Targets
0.10Suggestive
acute myeloid leukemiaOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZCCHC4Protein interaction100%METTL13Protein interaction100%SMAD3Protein interaction100%H3C12Protein interaction99%SMAD2Protein interaction98%ALKBH1Protein interaction93%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
70%
Liver
67%
Ovary
56%
Brain
55%
Lung
39%
Gene Interaction Network
Click a node to explore
METTL14ZCCHC4METTL13SMAD3H3C12SMAD2ALKBH1
PROTEIN STRUCTURE
Preparing viewer…
PDB5IL2 · 1.61 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.76LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.50 [0.34–0.76]
RankingsWhere METTL14 stands among ~20K protein-coding genes
  • #3,001of 20,598
    Most Researched151 · top quartile
  • #6,094of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedMETTL14
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A comprehensive review of m6A/m6Am RNA methyltransferase structures.
PMID: 34023900
Nucleic Acids Res · 2021
1.00
2
METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer.
PMID: 32552762
Mol Cancer · 2020
0.90
3
A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.
PMID: 24316715
Nat Chem Biol · 2014
0.80
4
RNA m6A modification, signals for degradation or stabilisation?
PMID: 38629637
Biochem Soc Trans · 2024
0.70
5
Methyltransferase-like proteins in cancer biology and potential therapeutic targeting.
PMID: 37533128
J Hematol Oncol · 2023
0.60