MRM3

Chr 17

mitochondrial rRNA methyltransferase 3

Also known as: RMTL1, RNMTL1

NCBI Gene: 55178ENSG00000171861UniProt: Q9HC36

Efficient translation of mitochondrial-derived transcripts requires proper assembly of the large subunit of the mitochondrial ribosome. Central to the biogenesis of this large subunit is the A-loop of mitochondrial 16S rRNA, which is modified by three rRNA methyltransferases located near mtDNA nucleoids. The protein encoded by this gene methylates G(1370) of 16S rRNA, and this modification is necessary for proper ribosomal large subnit assembly. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

125
ClinVar variants
60
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MRM3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 Pathogenic / Likely Pathogenic· 56 VUS of 125 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
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.
1.42LOEUF
pLI 0.000
Z-score 0.30
OE 0.92 (0.61–1.42)
Tolerant

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.
-0.27Z-score
OE missense 1.05 (0.95–1.16)
266 obs / 253.8 exp
Tolerant

Tolerant to missense variation

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.0.92 (0.61–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.95–1.16)
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.1.08
0≤1.21.6
LoF obs/exp: 15 / 16.3Missense obs/exp: 266 / 253.8Syn Z: -0.65

ClinVar Variant Classifications

125 submitted variants in ClinVar

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
Total—117

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The current status of clinical proteomics and the use of MRM and MRM(3) for biomarker validation.
Lemoine J et al.·Expert Rev Mol Diagn
2012Review
Multiple reaction monitoring and multiple reaction monitoring cubed based assays for the quantitation of apolipoprotein F.
Kumar A et al.·J Chromatogr B Analyt Technol Biomed Life Sci
2016
A Targeted LC-MRM(3) Proteomic Approach for the Diagnosis of SARS-CoV-2 Infection in Nasopharyngeal Swabs.
Drouin N et al.·Mol Cell Proteomics
2024
Quantitative analytical method for determining the levels of gastric inhibitory polypeptides GIP1-42 and GIP3-42 in human plasma using LC-MS/MS/MS.
Miyachi A et al.·J Proteome Res
2013
Isotope dilution direct injection mass spectrometry method for determination of four tyrosine kinase inhibitors in human plasma.
Mičová K et al.·Talanta
2012
Multiple reaction monitoring cubed for protein quantification at the low nanogram/milliliter level in nondepleted human serum.
Fortin T et al.·Anal Chem
2009
Evaluation of multiple reaction monitoring cubed performed by a quadrupole-linear ion trap mass spectrometer for quantitative determination of 6-sulfatoxymelatonin in urine.
Lopukhov LV et al.·J Chromatogr B Analyt Technol Biomed Life Sci
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Novel Liquid Chromatography Tandem Mass Spectrometry Technique using Multi-Period-Multi-Experiment of MRM-EPI-MRM3 with Library Matching for Simultaneous Determination of Amphetamine Type Stimulants Related Drugs in Whole Blood, Urine and Dried Blood Stain (DBS)-Application to Forensic Toxicology Cases in Malaysia.
Zubaidi FA et al.·J Anal Toxicol
2019Cohort
Multiple reaction monitoring with multistage fragmentation (MRM3) detection enhances selectivity for LC-MS/MS analysis of plasma free metanephrines.
Wright MJ et al.·Clin Chem
2015
MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome.
Rorbach J et al.·Mol Biol Cell
2014🔓 Open Access
Overcoming biofluid protein complexity during targeted mass spectrometry detection and quantification of protein biomarkers by MRM cubed (MRM3).
Jeudy J et al.·Anal Bioanal Chem
2014
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools