MRPL39
Chr 21ARmitochondrial ribosomal protein L39
Also known as: C21orf92, COXPD59, L39mt, L5mt, MRP-L5, MRPL5, MSTP003, PRED22
This protein is a component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins essential for oxidative phosphorylation within mitochondria. Mutations cause combined oxidative phosphorylation deficiency 59, an autosomal recessive mitochondrial disorder. The gene shows low constraint to loss-of-function variation (pLI near 0), consistent with its recessive inheritance pattern.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
145 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 | 65 | 0 | 65 |
Likely Pathogenic | 0 | 1 | 5 | 0 | 6 |
VUS | 0 | 49 | 7 | 0 | 56 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 0 | 51 | 78 | 0 | 130 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MRPL39 · 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