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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MTERF4
mitochondrial transcription termination factor 4
Chromosome 2 · 2q37.3
NCBI Gene: 130916Ensembl: ENSG00000122085.17HGNC: HGNC:28785UniProt: B4DFP7
35PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrial large ribosomal subunit assemblyprotein bindingmitochondrionrRNA bindingAbnormality of the skeletal systemcarpal tunnel syndromeovarian dysfunctionLeber hereditary optic neuropathy
✦AI Summary

MTERF4 (mitochondrial transcription termination factor 4) is a critical regulator of mitochondrial ribosome biogenesis and translation. The protein functions as a scaffold that recruits the RNA methyltransferase NSUN4 to the large mitochondrial ribosomal subunit (39S) 1, facilitating essential rRNA modifications required for ribosome assembly 2. MTERF4 contains structurally repeated MTERF-motifs forming a nucleic acid binding domain that creates an RNA binding path for both MTERF4 and NSUN4 1, and mutations disrupting this complex formation impair mitochondrial ribosome biogenesis 3. MTERF4 regulates expression of mitochondrial DNA-encoded respiratory chain proteins by controlling mitochondrial translation 4. In brown adipocytes, MTERF4 is essential for oxidative phosphorylation complex assembly and thermogenic capacity; MTERF4 deficiency impairs complex I, III, and IV assembly and reduces respiratory capacity 4. Beyond thermogenesis, MTERF4 dysfunction is implicated in neurodegenerative diseases: knockdown worsens MPP⁺-induced mitochondrial dysfunction in Parkinson's disease models 5, and MTERF4 overexpression promotes amyloidogenic APP processing in Alzheimer's disease models 6. These findings establish MTERF4 as a key regulator of mitochondrial protein synthesis with relevance to metabolic and neurodegenerative diseases.

Sources cited
1
MTERF4 recruits NSUN4 to large ribosomal subunit; structure reveals MTERF-motifs forming nucleic acid binding domain
PMID: 22949673
2
MTERF4 strongly stimulates NSUN4 methyltransferase specificity during rRNA modification
PMID: 23022348
3
MTERF4 mutations disrupt binding to large subunit and activate mitochondrial stress responses
PMID: 34609277
4
MTERF4 deficiency in brown adipocytes impairs OxPhos complex assembly and thermogenic capacity
PMID: 30690068
5
MTERF4 regulates mitochondrial dysfunction induced by MPP⁺ in Parkinson's disease models
PMID: 26102036
6
MTERF4 overexpression promotes amyloidogenic APP processing in Alzheimer's disease models
PMID: 27894840
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.50Moderate
carpal tunnel syndromeOpen Targets
0.35Weak
ovarian dysfunctionOpen Targets
0.07Suggestive
Leber hereditary optic neuropathyOpen Targets
0.04Suggestive
retinitis pigmentosa 71Open Targets
0.03Suggestive
retinitis pigmentosaOpen Targets
0.03Suggestive
VertigoOpen Targets
0.02Suggestive
preeclampsiaOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
diffuse large B-cell lymphomaOpen Targets
0.01Suggestive
neurodegenerative diseaseOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
bipolar disorderOpen Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
non-small cell lung carcinomaOpen Targets
0.00Suggestive
schizophreniaOpen Targets
0.00Suggestive
Insulin resistanceOpen Targets
0.00Suggestive
laryngotracheoesophageal cleftOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MRPL9Protein interaction100%MRPL19Protein interaction100%MRPL27Protein interaction100%MRPL20Protein interaction100%TUFMProtein interaction100%MRPL13Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Liver
66%
Bone Marrow
63%
Heart
61%
Lung
60%
Brain
38%
Gene Interaction Network
Click a node to explore
MTERF4MRPL9MRPL19MRPL27MRPL20TUFMMRPL13
PROTEIN STRUCTURE
Preparing viewer…
PDB4FZV · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.47–1.04]
RankingsWhere MTERF4 stands among ~20K protein-coding genes
  • #11,015of 20,598
    Most Researched35
  • #10,316of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedMTERF4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Adipocyte MTERF4 regulates non-shivering adaptive thermogenesis and sympathetic-dependent glucose homeostasis.
PMID: 30690068
Biochim Biophys Acta Mol Basis Dis · 2019
1.00
2
Structure of the human MTERF4-NSUN4 protein complex that regulates mitochondrial ribosome biogenesis.
PMID: 22949673
Proc Natl Acad Sci U S A · 2012
0.90
3
Visualizing formation of the active site in the mitochondrial ribosome.
PMID: 34609277
Elife · 2021
0.80
4
MTERF4 regulates the mitochondrial dysfunction induced by MPP(+) in SH-SY5Y cells.
PMID: 26102036
Biochem Biophys Res Commun · 2015
0.70
5
The human Obg protein GTPBP10 is involved in mitoribosomal biogenesis.
PMID: 30085210
Nucleic Acids Res · 2018
0.60