MRPL51
Chr 12mitochondrial ribosomal protein L51
Also known as: CDA09, HSPC241, MRP64, bMRP64, mL51
The protein is a component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins within mitochondria. Mutations cause Combined Oxidative Phosphorylation Deficiency 51, a severe mitochondrial disorder with autosomal recessive inheritance that typically presents in infancy with developmental delay, seizures, and lactic acidosis. The gene shows low constraint against loss-of-function variants (pLI 0.03), consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
89 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 42 | 0 | 42 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 21 | 11 | 0 | 32 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 21 | 56 | 0 | 77 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MRPL51 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools