MRPS22

Chr 3AR

mitochondrial ribosomal protein S22

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

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.

Summary from RefSeq, OMIM, UniProt, Mechanism
Research Assistant →

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 5MIM #611719
AR
Ovarian dysgenesis 7MIM #618117
AR
0
Active trials
3
Pubs (1 yr)
53
P/LP submissions
5%
P/LP missense
0.89
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryMRPS22
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 112 VUS of 266 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 1.93
OE 0.54 (0.340.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.97 (0.871.10)
198 obs / 203.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.340.89)
00.351.4
Missense OE0.97 (0.871.10)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 11 / 20.4Missense obs/exp: 198 / 203.2Syn Z: -1.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMRPS22-related combined oxidative phosphorylation deficiencyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6745th %ile
GOF
0.6443th %ile
LOF
0.2871th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

266 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic7
VUS112
Likely Benign63
Benign26
Conflicting14
36
Pathogenic
7
Likely Pathogenic
112
VUS
63
Likely Benign
26
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
27
0
36
Likely Pathogenic
3
1
3
0
7
VUS
4
94
12
2
112
Likely Benign
0
4
38
21
63
Benign
0
1
25
0
26
Conflicting
14
Total1510110523258

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

View in ClinVar →

Protein Context — Lollipop Plot

MRPS22 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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