MRPS2

Chr 9AR

mitochondrial ribosomal protein S2

Also known as: CGI-91, COXPD36, MRP-S2, S2mt, uS2m

NCBI Gene: 51116 ENSG00000122140 UniProt: Q9Y399 OMIM: 611971

The protein is required for mitoribosome formation and stability, and mitochondrial translation as a component of the small 28S mitochondrial ribosomal subunit. Mutations cause combined oxidative phosphorylation deficiency 36 through autosomal recessive inheritance. The pathogenic mechanism involves impaired mitochondrial protein synthesis leading to defective oxidative phosphorylation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 S2 family. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.861 OMIM phenotype

Clinical Summary— MRPS2

🧬

Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 75 VUS of 140 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?

1.86LOEUF

pLI 0.000

Z-score -0.58

OE 1.23 (0.73–1.86)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.88–1.11)

197 obs / 199.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.23 (0.73–1.86)

0≤0.351.4

Missense OE?0.99 (0.88–1.11)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 9 / 7.3Missense obs/exp: 197 / 199.9Syn Z: -0.80

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS75

Likely Benign38

Benign8

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	2	1	0	0	3
VUS	1	71	3	0	75
Likely Benign	0	3	10	25	38
Benign	0	7	0	1	8
Conflicting	—				7
Total	3	83	13	26	132

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap MRPS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →