MRPS11

Chr 15

mitochondrial ribosomal protein S11

Also known as: HCC-2, MRP-S11, S11mt, uS11m

NCBI Gene: 64963 ENSG00000181991 UniProt: P82912

This gene encodes a ribosomal protein component of the mitochondrial 28S ribosomal subunit that is essential for protein synthesis within mitochondria. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in mitochondrial protein production.

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 28S subunit protein that contains a high level of sequence similarity with ribosomal protein S11P family members. A pseudogene corresponding to this gene is found on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.68

LOEUF

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?

1.68LOEUF

pLI 0.000

Z-score -0.12

OE 1.04 (0.65–1.68)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.93 (0.80–1.09)

111 obs / 118.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.65–1.68)

0≤0.351.4

Missense OE?0.93 (0.80–1.09)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 11 / 10.6Missense obs/exp: 111 / 118.7Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in MRPS11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

297 rare PASS variants

Rare truncating (LoF)

1 in 4,400

57 rare PASS variants

Rare synonymous (reference)

1 in 410

116 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPS11. 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 180	1 in 4,600
South Asian	~43k	1 in 190	1 in 4,300
Remaining (unassigned)	~30k	1 in 170	1 in 3,800
European (Finnish)	~27k	1 in 1,200	none seen
Admixed American	~22k	1 in 350	1 in 2,500
African / African American	~21k	1 in 170	1 in 1,400
East Asian	~20k	1 in 280	1 in 1,900
Ashkenazi Jewish	~13k	1 in 1,900	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 410	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓