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GeneE
8 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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MRPS34
mitochondrial ribosomal protein S34
Chromosome 16 Β· 16p13.3
NCBI Gene: 65993Ensembl: ENSG00000074071.15HGNC: HGNC:16618UniProt: C9JJ19
129PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
structural constituent of ribosomemitochondrial translationmitochondrionmitochondrial small ribosomal subunitMitochondrial disorder due to a defect in mitochondrial protein synthesisgenetic disorderneurodegenerative diseaseLeigh syndrome
✦AI Summary

MRPS34 is a mitochondria-specific ribosomal protein essential for mitochondrial translation and mitoribosme assembly. It is required for stability of the small ribosomal subunit and the 12S rRNA 1. MRPS34 mutations compromise synthesis of all 13 mitochondrially-encoded polypeptides, reducing levels of mitochondrial respiratory complexes and decreasing oxygen consumption and respiratory chain enzyme activity 12. The protein may be trafficked to mitochondria through interactions with scaffolding proteins prior to mitochondrial entry 3. Pathogenic biallelic MRPS34 mutations cause Combined Oxidative Phosphorylation Deficiency 32 (COXPD32), typically presenting in infancy with developmental delay, feeding difficulties, lactic acidosis, and neurological manifestations including dystonia and ocular symptoms 4. Brain MRI characteristically shows symmetrical abnormal signals in the brainstem, thalamus, and basal ganglia 4. Recently, MRPS34 variants have been identified in adult-onset leukoencephalopathy with cerebellar ataxia, motor neuropathy, and profound cerebral folate deficiency, where folinic acid treatment induced clinical stabilization 5. Disease severity ranges from developmental delay with childhood survival to severe presentations with respiratory and circulatory failure 4. The underlying mechanism involves impaired small mitoribosomal subunit assembly and destabilization of actively translating ribosomes, leading to reduced OXPHOS enzyme activity across multiple tissues 12.

Sources cited
1
MRPS34 is required for stability of 12S rRNA and small ribosomal subunit; mutations compromise synthesis of all 13 mitochondrially-encoded polypeptides and reduce respiratory complex activity
PMID: 25816300
2
Biallelic MRPS34 mutations cause Leigh syndrome with combined OXPHOS defects through destabilization of small mitoribosomal subunit
PMID: 28777931
3
MRPS34 mutations cause COXPD32 presenting with developmental delay, feeding difficulties, lactic acidosis, dystonia, and brainstem/thalamic MRI abnormalities; disease severity ranges from childhood survival to fatal respiratory failure
PMID: 37385809
4
MRPS34 variants cause adult-onset leukoencephalopathy with cerebellar ataxia, motor neuropathy, and cerebral folate deficiency; folinic acid treatment improves outcomes
PMID: 41506652
5
MRPS34 interacts with hDLG scaffolding protein, potentially involved in mitochondrial trafficking of MRPS34
PMID: 12507520
Disease Associationsβ“˜21
Mitochondrial disorder due to a defect in mitochondrial protein synthesisOpen Targets
0.74Strong
genetic disorderOpen Targets
0.47Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
Leigh syndromeOpen Targets
0.31Weak
mitochondrial diseaseOpen Targets
0.12Weak
Distal myopathy, Nonaka typeOpen Targets
0.04Suggestive
myopathy, distal, 5Open Targets
0.04Suggestive
autosomal recessive limb-girdle muscular dystrophy type 2LOpen Targets
0.04Suggestive
distal myopathyOpen Targets
0.04Suggestive
Distal myotilinopathyOpen Targets
0.04Suggestive
myofibrillar myopathy 3Open Targets
0.04Suggestive
GNE myopathyOpen Targets
0.04Suggestive
myopathy, distal, 7, adult-onset, X-linkedOpen Targets
0.03Suggestive
myopathy, distal, 6, adult-onset, autosomal dominantOpen Targets
0.03Suggestive
myopathy, sarcoplasmic bodyOpen Targets
0.03Suggestive
inclusion body myopathy and brain white matter abnormalitiesOpen Targets
0.03Suggestive
tibial muscular dystrophyOpen Targets
0.03Suggestive
inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3Open Targets
0.03Suggestive
autosomal recessive limb-girdle muscular dystrophy type 2DOpen Targets
0.03Suggestive
autosomal dominant mitochondrial myopathy with exercise intoleranceOpen Targets
0.03Suggestive
Combined oxidative phosphorylation deficiency 32UniProt
Pathogenic Variants10
NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)Pathogenic
Combined oxidative phosphorylation deficiency 32|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 32
NM_023936.2(MRPS34):c.322-10G>APathogenic
Combined oxidative phosphorylation deficiency 32|not provided|Ovarian serous cystadenocarcinoma
β˜…β˜…β˜†β˜†2025
NM_023936.2(MRPS34):c.320_321insAGTA (p.Asn108fs)Pathogenic
MRPS34-related disorder|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 108
NM_023936.2(MRPS34):c.164G>A (p.Trp55Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 55
NM_023936.2(MRPS34):c.322-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NC_000016.10:g.1772495_1773356delPathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_023936.2(MRPS34):c.532C>T (p.Arg178Ter)Likely pathogenic
Combined oxidative phosphorylation deficiency 32
β˜…β˜†β˜†β˜†2022β†’ Residue 178
NM_023936.2(MRPS34):c.562G>A (p.Glu188Lys)Likely pathogenic
Combined oxidative phosphorylation deficiency 32
β˜…β˜†β˜†β˜†2022β†’ Residue 188
NM_023936.2(MRPS34):c.37G>A (p.Glu13Lys)Likely pathogenic
Leigh syndrome|Combined oxidative phosphorylation deficiency 32
β˜…β˜†β˜†β˜†2018β†’ Residue 13
NM_023936.1(MRPS34):c.321+1G>TPathogenic
Combined oxidative phosphorylation deficiency 32|Leigh syndrome
β˜†β˜†β˜†β˜†2017
View on ClinVar β†—
Related Genes
GATBShared pathway100%MRPL46Shared pathway100%MRPL39Shared pathway100%MRPL50Shared pathway100%MRPL54Shared pathway100%MRPL53Shared pathway100%
Tissue Expression6 tissues
Liver
100%
Brain
52%
Lung
49%
Ovary
40%
Heart
39%
Bone Marrow
37%
Gene Interaction Network
Click a node to explore
MRPS34GATBMRPL46MRPL39MRPL50MRPL54MRPL53
PROTEIN STRUCTURE
Preparing viewer…
PDB7QI4 Β· 2.21 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.89LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.39 [0.93–1.89]
RankingsWhere MRPS34 stands among ~20K protein-coding genes
  • #3,630of 20,598
    Most Researched129 Β· top quartile
  • #2,840of 5,498
    Most Pathogenic Variants10
  • #17,178of 17,882
    Most Constrained (LOEUF)1.89
Genes detectedMRPS34
Sources retrieved8 papers
Response timeβ€”
πŸ“„ Sources
8β–Ό
1
[A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review].
PMID: 37385809
Zhonghua Er Ke Za Zhi Β· 2023
1.00
2
Mutation in MRPS34 compromises protein synthesis and causes mitochondrial dysfunction.
PMID: 25816300
PLoS Genet Β· 2015
0.88
3
MRPS Genes Causing Leukoencephalopathy With Profound Cerebral Folate Deficiency in Adults.
PMID: 41506652
J Inherit Metab Dis Β· 2026
0.75
4
Regulation of the tubulin polymerization-promoting protein by Ca
PMID: 33831707
Cell Calcium Β· 2021
0.63
5
Benzyl isothiocyanate alters the gene expression with cell cycle regulation and cell death in human brain glioblastoma GBM 8401 cells.
PMID: 26781422
Oncol Rep Β· 2016
0.50