MRPL41

Chr 9

mitochondrial ribosomal protein L41

Also known as: BMRP, MRP-L27, MRPL27, PIG3, RPML27, mL41

NCBI Gene: 64975 ENSG00000182154 UniProt: Q8IXM3 OMIM: 611846

This protein is a component of the mitochondrial ribosome large subunit and is involved in mitochondrial protein synthesis, while also playing roles in apoptosis and cell cycle regulation by enhancing p53 stability and promoting cell cycle arrest. Mutations in MRPL41 cause autosomal recessive mitochondrial disease with features including developmental delay, seizures, and metabolic dysfunction. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in mitochondrial function.

OMIM ResearchSummary from RefSeq, UniProt

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the YmL27 ribosomal protein family. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.17

Clinical Summary— MRPL41

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

21 VUS of 21 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.17LOEUF

pLI 0.555

Z-score 1.45

OE 0.00 (0.00–1.17)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.42Z-score

OE missense 0.86 (0.70–1.06)

60 obs / 69.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.17)

0≤0.351.4

Missense OE?0.86 (0.70–1.06)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 0 / 2.4Missense obs/exp: 60 / 69.8Syn Z: -0.64

This gene — mechanism propensity

0.6455th %ile

GOF

0.5072th %ile

LOF

0.4038th %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

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	21	21
Likely Benign	0	0
Benign	0	0
Total	21	21

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

View in ClinVar →

129 pathogenic / likely-pathogenic (of 145) ClinVar copy-number / structural variants overlap MRPL41 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →