METTL15

Chr 11

methyltransferase 15, mitochondrial 12S rRNA N4-cytidine

Also known as: METT5D1

NCBI Gene: 196074ENSG00000169519UniProt: A6NJ78

This protein is an N4-methylcytidine methyltransferase that methylates mitochondrial 12S rRNA at position C839, facilitating assembly of mitochondrial small ribosomal subunits. Mutations cause autosomal recessive intellectual developmental disorder with short stature, facial dysmorphism, and speech delay. The gene is extremely intolerant to loss-of-function variation, reflecting its essential role in mitochondrial protein synthesis.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
19
P/LP submissions
0%
P/LP missense
1.33
LOEUF
DN
Mechanism· predicted
Clinical Summary— METTL15
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 67 VUS of 97 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.49
OE 0.88 (0.59–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.24Z-score
OE missense 1.05 (0.94–1.17)
235 obs / 224.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.88 (0.59–1.33)
0≤0.351.4
Missense OE1.05 (0.94–1.17)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 16 / 18.3Missense obs/exp: 235 / 224.8Syn Z: -0.59
DN
0.6454th %ile
GOF
0.4480th %ile
LOF
0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS67
Likely Benign6
19
Pathogenic
67
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
59
8
0
67
Likely Benign
0
4
2
0
6
Benign
0
0
0
0
0
Total06329092

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

METTL15 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients