MRPS34

Chr 16AR

mitochondrial ribosomal protein S34

Also known as: COXPD32, MRP-S12, MRP-S34, mS34

NCBI Gene: 65993 ENSG00000074071 UniProt: P82930 OMIM: 611994

This protein is required for mitochondrial translation and maintains the stability of the small ribosomal subunit and 12S rRNA needed for mitoribosome formation. Mutations cause combined oxidative phosphorylation deficiency 32, inherited in an autosomal recessive pattern. The gene shows relatively low constraint to loss-of-function variation (pLI 0.003, LOEUF 1.72).

GeneReviews 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.721 OMIM phenotype

Clinical Summary— MRPS34

🧬

Gene-Disease Validity (ClinGen)

Leigh syndrome · 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

10 unique Pathogenic / Likely Pathogenic· 65 VUS of 137 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — MRPS34

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.72LOEUF

pLI 0.003

Z-score 0.33

OE 0.84 (0.41–1.72)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.43Z-score

OE missense 1.41 (1.23–1.63)

135 obs / 95.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.41–1.72)

0≤0.351.4

Missense OE?1.41 (1.23–1.63)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 4 / 4.8Missense obs/exp: 135 / 95.7Syn Z: -1.76

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMRPS34-related Leigh syndrome with instability of the small mitoribosomal subunitLOFAR

This gene — mechanism propensity

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

0.4884th %ile

GOF

0.77top 25%

LOF

0.3549th %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

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic7

VUS65

Likely Benign44

Benign13

Conflicting1

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	2	0	1	0	3
Likely Pathogenic	5	2	0	0	7
VUS	1	62	2	0	65
Likely Benign	0	4	8	32	44
Benign	1	4	4	4	13
Conflicting	—				1
Total	9	72	15	36	133

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap MRPS34 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →