MRM2

Chr 7AR

mitochondrial rRNA methyltransferase 2

Also known as: FJH1, FTSJ2, HEL97, MTDPS17, RRMJ2

NCBI Gene: 29960 ENSG00000122687 UniProt: Q9UI43 OMIM: 606906

MRM2 encodes an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes 2'-O-methylation of mitochondrial ribosomal RNA and is essential for mitochondrial ribosome assembly and respiratory function. Biallelic mutations cause mitochondrial DNA depletion syndrome 17 with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the S-adenosylmethionine-binding protein family. It is a nucleolar protein and it may be involved in the processing and modification of rRNA. This gene has been suggested to be involved in cell cycle control and DNA repair. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.571 OMIM phenotype

Clinical Summary— MRM2

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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

2 unique Pathogenic / Likely Pathogenic· 5 VUS of 20 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?

1.57LOEUF

pLI 0.000

Z-score 0.46

OE 0.82 (0.45–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.86–1.12)

150 obs / 153.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.45–1.57)

0≤0.351.4

Missense OE?0.98 (0.86–1.12)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 6 / 7.3Missense obs/exp: 150 / 153.0Syn Z: -0.37

This gene — mechanism propensity

0.6839th %ile

GOF

0.4579th %ile

LOF

0.3261th %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

20 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS5

Likely Benign5

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	0	5	0	0	5
Likely Benign	0	0	1	4	5
Benign	0	2	0	1	3
Total	1	8	1	5	15

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap MRM2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →