MRPS15

Chr 1

mitochondrial ribosomal protein S15

Also known as: DC37, MPR-S15, RPMS15, S15mt, uS15m

NCBI Gene: 64960 ENSG00000116898 UniProt: P82914 OMIM: 611979

This protein is a component of the mitochondrial ribosome's small 28S subunit and functions in mitochondrial protein synthesis by binding to 12S rRNA. Mutations cause autosomal recessive mitochondrial respiratory chain deficiency, typically presenting in infancy with growth retardation, developmental delay, and multi-organ involvement including neurological and cardiac manifestations. The gene is highly intolerant to loss-of-function mutations, indicating critical importance for cellular function.

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 belongs to the ribosomal protein S15P family. The encoded protein is more than two times the size of its E. coli counterpart, with the 12S rRNA binding sites conserved. Between human and mouse, the encoded protein is the least conserved among small subunit ribosomal proteins. Pseudogenes corresponding to this gene are found on chromosomes 15q and 19q. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.43

Clinical Summary— MRPS15

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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

46 VUS of 69 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.27

OE 0.93 (0.62–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.92 (0.80–1.06)

136 obs / 148.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.93 (0.62–1.43)

0≤0.351.4

Missense OE?0.92 (0.80–1.06)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 15 / 16.2Missense obs/exp: 136 / 148.0Syn Z: 0.76

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS46

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	46	0	46
Likely Benign	4	1	5
Benign	0	0	0
Total	50	1	51

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap MRPS15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →