MRPS28

Chr 8AR

mitochondrial ribosomal protein S28

Also known as: COXPD47, HSPC007, MRP-S28, MRP-S35, MRPS35

The protein is a component of the mitochondrial ribosome's small 28S subunit, functioning in mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 47, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI 0.00005, LOEUF 1.9), suggesting tolerance to haploinsufficiency.

Summary from RefSeq, OMIM
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Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 47MIM #618958
AR
0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.88
LOEUF
DN
Mechanism· predicted
Clinical SummaryMRPS28
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.000
Z-score -0.40
OE 1.19 (0.631.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.03Z-score
OE missense 1.01 (0.861.19)
104 obs / 103.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.19 (0.631.88)
00.351.4
Missense OE1.01 (0.861.19)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 6 / 5.0Missense obs/exp: 104 / 103.2Syn Z: -1.23
DN
0.7131th %ile
GOF
0.5269th %ile
LOF
0.4429th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MRPS28 · 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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