MRPL57

Chr 13

mitochondrial ribosomal protein L57

Also known as: MRP63, bMRP63, mL63

NCBI Gene: 78988ENSG00000173141UniProt: Q9BQC6OMIM: 611997

This protein is a component of mitochondrial ribosomes, which synthesize proteins within mitochondria. Mutations cause autosomal recessive severe infantile mitochondrial disease with growth retardation, hearing loss, and intellectual disability. The gene shows tolerance to loss-of-function variants (pLI 0.14), consistent with recessive inheritance requiring biallelic mutations to cause disease.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.77
Clinical Summary— MRPL57
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.14) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 33 VUS of 83 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
1.77LOEUF
pLI 0.139
Z-score 0.59
OE 0.53 (0.18–1.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.17 (0.97–1.41)
78 obs / 66.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.53 (0.18–1.77)
0≤0.351.4
Missense OE1.17 (0.97–1.41)
0≤0.61.4
Synonymous OE1.26
0≤1.21.6
LoF obs/exp: 1 / 1.9Missense obs/exp: 78 / 66.6Syn Z: -1.12
DN
0.6356th %ile
GOF
0.7126th %ile
LOF
0.4038th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS33
Likely Benign6
42
Pathogenic
2
Likely Pathogenic
33
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
22
11
0
33
Likely Benign
0
1
5
0
6
Benign
0
0
0
0
0
Total02360083

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

View in ClinVar →

Protein Context — Lollipop Plot

MRPL57 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients