METTL6
Chr 3methyltransferase 6, tRNA N3-cytidine
Also known as: hMETTL6
METTL6 encodes an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes N(3)-methylcytidine modification at position 32 of the anticodon loop in serine tRNAs. The gene shows minimal constraint against loss-of-function variants (pLI 0.00002, LOEUF 1.18), and no established disease associations have been reported for mutations in this gene. Clinical significance of METTL6 variants remains uncertain given the lack of constraint and absence of documented pathogenic mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
83 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 46 | 1 | 0 | 47 |
Likely Benign | 0 | 0 | 1 | 1 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 46 | 25 | 1 | 72 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
METTL6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools