METTL2A
Chr 17methyltransferase 2A, tRNA N3-cytidine
Also known as: METTL2
Enables tRNA (cytidine-3-)-methyltransferase activity. Involved in tRNA methylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
Clinical Summary— METTL2A
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
12 Pathogenic / Likely Pathogenic· 55 VUS of 69 total submissions
Some data sources returned errors (1)
pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.35LOEUF
pLI 0.000
Z-score 0.30
OE 0.93 (0.65–1.35)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.07Z-score
OE missense 0.99 (0.88–1.11)
199 obs / 202.0 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.93 (0.65–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.88–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 20 / 21.5Missense obs/exp: 199 / 202.0Syn Z: 0.91
ClinVar Variant Classifications
69 submitted variants in ClinVar
Classification Summary
Pathogenic10
Likely Pathogenic2
VUS55
Likely Benign2
10
Pathogenic
2
Likely Pathogenic
55
VUS
2
Likely Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 54 | 1 | 0 | 55 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 56 | 13 | 0 | 69 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
METTL2A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
METHYLTRANSFERASE 2A, METHYLCYTIDINE; METTL2A
MIM #618902 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Nanopore direct RNA sequencing reveals METTL2A-mediated m3C sites in poly(A) RNA.
Mitsutomi S et al.·Genome Res
2025
Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast Cancer.
Wang S et al.·J Transl Med
2022Open Access
Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6.
Mao XL et al.·Nucleic Acids Res
2021Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
m3C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response
Cui J et al.·Nat Commun
2024
Development and Validation of Diagnostic Models for Transcriptomic Signature Genes for Multiple Tissues in Osteoarthritis
Gao Q et al.·J Inflamm Res
2024Functional
Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs
Lentini JM et al.·J Biol Chem
2022
Mitochondrial RNA m3C methyltransferase METTL8 relies on an isoform-specific N-terminal extension and modifies multiple heterogenous tRNAs.
Huang MH et al.·Sci Bull (Beijing)
2023
Nomogram Based on A-To-I RNA Editing for Predicting Overall Survival in Patients With Breast Cancer
Zhang Y et al.·J Cell Mol Med
2025Cohort
Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8
Huang MH et al.·Nucleic Acids Res
2022
Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
Campeanu IJ et al.·Sci Rep
2021Functional
Top 7 full-text resultsSearch PubTator3 ↗
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