MRPS22

Chr 3

mitochondrial ribosomal protein S22

Also known as: C3orf5, COXPD5, GIBT, GK002, MRP-S22, ODG7, RPMS22, mS22

NCBI Gene: 56945 ENSG00000175110 UniProt: P82650

MRPS22 encodes a protein component of the mitochondrial ribosome small subunit (28S) that is essential for mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 5 and ovarian dysgenesis 7 through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function effects that disrupt normal mitochondrial ribosome function and subsequent oxidative phosphorylation.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 does not seem to have a counterpart in prokaryotic and fungal-mitochondrial ribosomes. This gene lies telomeric of and is transcribed in the opposite direction from the forkhead box L2 gene. A pseudogene corresponding to this gene is found on chromosome Xq. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 5

UniProtOvarian dysgenesis 7

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

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?

0.89LOEUF

pLI 0.000

Z-score 1.93

OE 0.54 (0.34–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.87–1.10)

198 obs / 203.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.34–0.89)

0≤0.351.4

Missense OE?0.97 (0.87–1.10)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 11 / 20.4Missense obs/exp: 198 / 203.2Syn Z: -1.44

Background carrier burden — how many people carry a rare variant somewhere in MRPS22?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

519 rare PASS variants

Rare truncating (LoF)

1 in 680

112 rare PASS variants

Rare synonymous (reference)

1 in 650

179 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPS22. 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 130	1 in 670
South Asian	~43k	1 in 90	1 in 2,200
Remaining (unassigned)	~30k	1 in 88	1 in 540
European (Finnish)	~27k	1 in 300	1 in 1,700
Admixed American	~22k	1 in 89	1 in 310
African / African American	~21k	1 in 110	1 in 290
East Asian	~20k	1 in 130	1 in 630
Ashkenazi Jewish	~13k	1 in 1,000	1 in 1,600
Middle Eastern	~2,884	1 in 76	1 in 360

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 8.? see exons ↓