MRM3

Chr 17

mitochondrial rRNA methyltransferase 3

Also known as: RMTL1, RNMTL1

NCBI Gene: 55178 ENSG00000171861 UniProt: Q9HC36 OMIM: 612600

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.42

Clinical Summary— MRM3

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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

4 VUS of 12 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?

1.42LOEUF

pLI 0.000

Z-score 0.30

OE 0.92 (0.61–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.27Z-score

OE missense 1.05 (0.95–1.16)

266 obs / 253.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.61–1.42)

0≤0.351.4

Missense OE?1.05 (0.95–1.16)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 15 / 16.3Missense obs/exp: 266 / 253.8Syn Z: -0.65

This gene — mechanism propensity

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

12 submitted variants in ClinVar

ClinVar

Classification Summary

VUS4

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	4	4
Likely Benign	0	0
Benign	0	0
Total	4	4

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 114) ClinVar copy-number / structural variants overlap MRM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →