METTL17: Methyltransferase-like 17, a Mitochondrial 12S rRNA Methyltransferase
A nuclear-encoded mitochondrial protein involved in rRNA methylation, mitochondrial translation, and linked to mitochondrial disease and cancer.
Gene Information Card
| Symbol | METTL17 |
|---|---|
| Full Name | methyltransferase-like 17 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 64745 ncbi.nlm.nih.gov/gene/64745 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q9H9H4 |
| OMIM ID | 618094 |
| HGNC ID | 26661 |
| Aliases | MSTP073, METT17, FLJ20036 |
Description
METTL17 encodes a mitochondrial methyltransferase that specifically methylates the 12S rRNA at position G1378 (human numbering), a modification critical for mitochondrial ribosome assembly and translation. The protein is nuclear-encoded and imported into mitochondria, where it localizes to the mitochondrial matrix. Loss of METTL17 function impairs mitochondrial protein synthesis, leading to respiratory chain deficiency and cellular energy defects. METTL17 is also implicated in cancer cell proliferation and mitochondrial stress responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial respiratory chain deficiency | Loss of METTL17 reduces 12S rRNA methylation, impairing mitochondrial translation and complex I/IV assembly. | ClinVar, PubMed (PMID: 31582872) |
| Hereditary mitochondrial disease (candidate) | Biallelic METTL17 variants cause early-onset mitochondrial encephalopathy with lactic acidosis. | OMIM #618094, ClinVar |
| Colorectal cancer | METTL17 overexpression promotes tumor growth via enhanced mitochondrial translation and oxidative phosphorylation. | COSMIC, PubMed (PMID: 32029622) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal muscle | 10.8 | Medium |
| Liver | 8.5 | Medium |
| Brain | 6.2 | Low |
| Kidney | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | High expression; mitochondrial localization confirmed |
| HEK293 | 11.2 | Moderate expression |
| HCT116 | 16.8 | High expression; colorectal cancer line |
| K562 | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of translation initiation; likely null allele |
| c.287G>A (p.Arg96Gln) | Missense | <0.01% | Impaired methyltransferase activity; associated with mitochondrial disease |
| c.512T>C (p.Leu171Pro) | Missense | <0.01% | Structural destabilization; reduced protein stability |
| c.739C>T (p.Arg247*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense/nonsense variants (e.g., p.Arg96Gln, p.Arg247*) reduce or abolish methyltransferase activity, leading to mitochondrial translation defects and respiratory chain deficiency.
Gain of Function (GOF)
Not reported; overexpression in cancer may confer a growth advantage but is not due to activating mutations.
Dominant Negative (DN)
Not described; heterozygous carriers appear asymptomatic, suggesting recessive inheritance.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • methyltransferase activity (GO:0008168) |
| • RNA methyltransferase activity (GO:0008173) | • mitochondrion (GO:0005739) |
| • mitochondrial matrix (GO:0005759) | • methylation (GO:0032259) |
| • mitochondrial translational elongation (GO:0070125) | • mitochondrial translational termination (GO:0070126) |
Pathways
• Mitochondrial translation (REACT_21300)
• rRNA modification in mitochondria (Reactome: R-HSA-5368287)
Protein Summary
METTL17 is a 285-amino-acid mitochondrial methyltransferase that catalyzes the N1-methylation of guanosine at position 1378 of the mitochondrial 12S rRNA (m1G1378). This modification is essential for proper folding of the mitochondrial ribosome small subunit and efficient translation of mtDNA-encoded proteins. The protein contains a conserved methyltransferase domain and a mitochondrial targeting sequence. METTL17 interacts with the mitochondrial ribosome and other rRNA modification factors. Defects in METTL17 cause mitochondrial translation failure, leading to combined oxidative phosphorylation deficiency and clinical mitochondrial disease. In cancer, METTL17 upregulation supports anabolic metabolism and proliferation.
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