MRPL57

Chr 13

mitochondrial ribosomal protein L57

Also known as: MRP63, bMRP63, mL63

NCBI Gene: 78988 ENSG00000173141 UniProt: Q9BQC6

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.

ResearchSummary from RefSeq

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 protein which belongs to an undetermined ribosomal subunit and which seems to be specific to animal mitoribosomes. Pseudogenes corresponding to this gene are found on chromosomes 1p, 1q, 3p, 5q, 8q, 14q, and Y. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.77

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.53 (0.18–1.77)

0≤0.351.4

Missense OE?1.17 (0.97–1.41)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 1 / 1.9Missense obs/exp: 78 / 66.6Syn Z: -1.12

Background carrier burden — how many people carry a rare variant somewhere in MRPL57?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

181 rare PASS variants

Rare truncating (LoF)

1 in 1,800

29 rare PASS variants

Rare synonymous (reference)

1 in 950

83 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MRPL57; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 450	1 in 1,700
South Asian	~43k	1 in 250	1 in 8,600
Remaining (unassigned)	~30k	1 in 320	1 in 2,500
European (Finnish)	~27k	1 in 450	≈ 1 in 8,200
Admixed American	~22k	1 in 230	1 in 860
African / African American	~21k	1 in 190	1 in 3,300
East Asian	~20k	1 in 210	1 in 1,900
Ashkenazi Jewish	~13k	≈ 1 in 3,300	1 in 1,300
Middle Eastern	~2,884	1 in 260	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓