MRPS11

Chr 15

mitochondrial ribosomal protein S11

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

NCBI Gene: 64963 ENSG00000181991 OMIM: 611977

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.68

Clinical Summary— MRPS11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

30 VUS of 38 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?

1.68LOEUF

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

This gene — mechanism propensity

0.6260th %ile

GOF

0.3293th %ile

LOF

0.4727th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	30	30
Likely Benign	2	2
Benign	0	0
Total	32	32

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap MRPS11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →