NSUN2: RNA Methyltransferase and Its Role in Development and Disease
Comprehensive genomic and proteomic overview of NSUN2, a key RNA 5-methylcytosine methyltransferase implicated in intellectual disability, microcephaly, and cancer.
Gene Information Card
| Symbol | NSUN2 |
|---|---|
| Full Name | NOP2/Sun RNA methyltransferase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5p15.31 |
| NCBI Gene ID | 54888 ncbi.nlm.nih.gov/gene/54888 |
| Ensembl ID | ENSG00000037474 |
| UniProt ID | Q08J23 |
| OMIM ID | 610916 |
| HGNC ID | 25994 |
| Aliases | MISU, SA37, TRM4, NOL1, NOP2/Sun domain family member 2 |
Description
NSUN2 encodes a methyltransferase that catalyzes the formation of 5-methylcytosine (m5C) in RNA, primarily targeting tRNAs and mRNAs. This modification influences RNA stability, translation efficiency, and cellular stress responses. NSUN2 is essential for normal brain development and cell proliferation; loss-of-function mutations cause autosomal recessive intellectual disability with microcephaly. Overexpression is observed in several cancers, suggesting an oncogenic role.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive intellectual disability with microcephaly | Loss-of-function mutations in NSUN2 impair tRNA methylation, leading to defective protein synthesis and neuronal development. | OMIM #611091; PMID: 22581968 |
| Breast cancer | NSUN2 overexpression promotes m5C modification of oncogene mRNAs, enhancing their stability and translation. | COSMIC; PMID: 28424480 |
| Squamous cell carcinoma | NSUN2 upregulation correlates with poor prognosis; drives proliferation via m5C-dependent mRNA regulation. | COSMIC; PMID: 29395067 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Brain | 15.2 | Medium |
| Liver | 10.8 | Medium |
| Heart | 7.3 | Low |
| Lung | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.4 | Cervical cancer cell line |
| HEK293 | 14.7 | Embryonic kidney cell line |
| MCF7 | 22.1 | Breast cancer cell line |
| HepG2 | 11.3 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.680C>T (p.Pro227Leu) | Missense | Rare | Loss of methyltransferase activity; associated with intellectual disability |
| c.1207C>T (p.Arg403*) | Nonsense | Rare | Premature truncation; loss of function; microcephaly |
| c.1445_1446del (p.Glu482Valfs*5) | Frameshift | Rare | Loss of function; intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Most reported NSUN2 mutations are loss-of-function, leading to reduced m5C methylation and impaired tRNA stability, causing neurodevelopmental disorders.
Gain of Function (GOF)
Not well documented; overexpression in cancer may act as a gain-of-function by increasing oncogenic mRNA methylation.
Dominant Negative (DN)
No evidence for dominant-negative effects; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • RNA methyltransferase activity (GO:0008173) | • tRNA binding (GO:0000049) |
| • tRNA methylation (GO:0030488) | • mRNA methylation (GO:0080009) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
Pathways
• tRNA modification in the nucleus and cytoplasm
• mRNA stability regulation via m5C
• Epitranscriptomic regulation of cell proliferation
Protein Summary
NSUN2 is a 767-amino-acid RNA methyltransferase that localizes to the nucleus and cytoplasm. It contains a conserved NOL1/NOP2/Sun domain responsible for methyl group transfer. The protein modifies tRNAs at position C34 and C48, and also methylates mRNAs to regulate their stability. NSUN2 interacts with RNA processing factors and is upregulated in response to cellular stress. Structural studies show a Rossmann-fold catalytic domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSUN2 Knockout HEK293 Cell Line | EDJ-KQ174 | Human | 54888 | Details Get a Quote |
| NSUN2 Knockout A-549 Cell Line | EDJ-KQ19956 | Human | 54888 | Details Get a Quote |
| NSUN2 Knockout HCT 116 Cell Line | EDJ-KQ19957 | Human | 54888 | Details Get a Quote |
| NSUN2 Knockout HeLa Cell Line | EDJ-KQ19958 | Human | 54888 | Details Get a Quote |
| NSUN2 Knockout Hep-G2 Cell Line | EDJ-KZ378 | Human | 54888 | Details Get a Quote |
| Nsun2 Knockout TC-1 Cell Line | EDC08254 | Mouse | 28114 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
