NSUN4 Gene - NOP2/Sun RNA Methyltransferase 4
Mitochondrial 16S rRNA m5C Methyltransferase and Ribosome Assembly Factor
Gene Information Card
| Symbol | NSUN4 |
|---|---|
| Full Name | NOP2/Sun RNA Methyltransferase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p33 |
| NCBI Gene ID | 387338 ncbi.nlm.nih.gov/gene/387338 |
| Ensembl ID | ENSG00000188994 |
| UniProt ID | Q96CB9 |
| OMIM ID | 615794 |
| HGNC ID | 26776 |
| Aliases | MGC10744, NOL1/NOP2/Sun domain family member 4 |
Description
NSUN4 encodes a member of the NOL1/NOP2/Sun (NSUN) family of RNA methyltransferases. The protein localizes to mitochondria and specifically methylates cytosine 911 in mitochondrial 16S rRNA (m5C911), a modification essential for mitochondrial ribosome assembly and function. NSUN4 also interacts with MTERF4 to facilitate ribosome biogenesis. Loss of NSUN4 leads to impaired mitochondrial translation and respiratory chain deficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial respiratory chain disorders | Defective 16S rRNA methylation impairs mitochondrial ribosome assembly and translation | PMID: 24652932 |
| Combined oxidative phosphorylation deficiency | NSUN4 mutations cause reduced mitochondrial translation and complex I-IV deficiency | PMID: 24652932 |
| Leigh syndrome (potential) | Mitochondrial dysfunction due to impaired ribosome biogenesis | PMID: 24652932 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 10.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 7.1 | Medium |
| Brain | 5.4 | Low |
| Testis | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 12.8 | High expression |
| HepG2 | 9.6 | Medium expression |
| K562 | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.337C>T (p.Arg113Trp) | Missense | Rare | Impaired methyltransferase activity |
| c.502G>A (p.Gly168Arg) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
NSUN4 loss-of-function mutations impair mitochondrial 16S rRNA methylation, leading to defective ribosome assembly and mitochondrial translation deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported for NSUN4.
Dominant Negative (DN)
No dominant-negative mutations reported for NSUN4.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • methyltransferase activity (GO:0008168) |
| • rRNA (cytosine-C5-)-methyltransferase activity (GO:0009383) | • mitochondrion (GO:0005739) |
| • methylation (GO:0032259) | • mitochondrial translational elongation (GO:0070125) |
Pathways
• Mitochondrial ribosome assembly (R-HSA-5368287)
• rRNA modification in mitochondria (R-HSA-6790901)
Protein Summary
NSUN4 is a 396-amino acid mitochondrial methyltransferase that catalyzes the formation of 5-methylcytosine (m5C) at position 911 of mitochondrial 16S rRNA. This modification is critical for the assembly of the large mitochondrial ribosomal subunit. NSUN4 forms a complex with MTERF4, which directs it to the 16S rRNA substrate. Without NSUN4, mitochondrial translation is severely impaired, leading to respiratory chain dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSUN4 Knockout HEK293 Cell Line | EDJ-KQ52273 | Human | 387338 | Details Get a Quote |
| NSUN4 Knockout HeLa Cell Line | EDJ-KQ59974 | Human | 387338 | Details Get a Quote |
| NSUN4 Knockout A-549 Cell Line | EDJ-KQ68436 | Human | 387338 | Details Get a Quote |
| NSUN4 Knockout HCT 116 Cell Line | EDJ-KQ76814 | Human | 387338 | Details Get a Quote |
