MRM3

Chr 17

mitochondrial rRNA methyltransferase 3

Also known as: RMTL1, RNMTL1

This gene encodes a methyltransferase that modifies mitochondrial 16S ribosomal RNA at position 1370, which is essential for proper assembly and function of the large subunit of mitochondrial ribosomes. Mutations cause Combined Oxidative Phosphorylation Deficiency 7, an autosomal recessive mitochondrial disorder presenting in infancy with severe developmental delay, hypotonia, and lactic acidosis. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.42
Clinical SummaryMRM3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 56 VUS of 125 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.000
Z-score 0.30
OE 0.92 (0.611.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.27Z-score
OE missense 1.05 (0.951.16)
266 obs / 253.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.92 (0.611.42)
00.351.4
Missense OE1.05 (0.951.16)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 15 / 16.3Missense obs/exp: 266 / 253.8Syn Z: -0.65
DN
0.6358th %ile
GOF
0.3986th %ile
LOF
0.2871th %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

125 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic6
VUS56
Likely Benign1
54
Pathogenic
6
Likely Pathogenic
56
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
54
Likely Pathogenic
6
VUS
56
Likely Benign
1
Benign
0
Total117

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MRM3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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