NSUN5: NOP2/Sun RNA Methyltransferase 5
A 5-methylcytosine RNA methyltransferase involved in ribosome biogenesis and neurodevelopmental disorders
Gene Information Card
| Symbol | NSUN5 |
|---|---|
| Full Name | NOP2/Sun RNA Methyltransferase 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q11.23 |
| NCBI Gene ID | 26033 ncbi.nlm.nih.gov/gene/26033 |
| Ensembl ID | ENSG00000106031 |
| UniProt ID | Q96P11 |
| OMIM ID | 615732 |
| HGNC ID | 29995 |
| Aliases | NOL1R, Nsun5, WBSCR20, WBSCR20A, p120 |
Description
NSUN5 encodes a member of the NOL1/NOP2/Sun (NSUN) family of RNA methyltransferases that catalyze 5-methylcytosine (m5C) modification of RNA. The protein localizes to the nucleolus and is involved in ribosome biogenesis, specifically methylating 28S rRNA at cytosine 3782. NSUN5 is located in the Williams-Beuren syndrome critical region on chromosome 7q11.23. Loss-of-function mutations are associated with autosomal recessive intellectual disability, microcephaly, and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 55 (MRT55) | Biallelic loss-of-function mutations in NSUN5 impair 28S rRNA methylation, leading to defective ribosome assembly and reduced protein synthesis in neurons. | PMID: 26216346 |
| Williams-Beuren syndrome (WBS) | NSUN5 is hemizygously deleted in the 1.5-1.8 Mb WBS critical region; haploinsufficiency may contribute to the neurodevelopmental phenotype. | OMIM #194050 |
| Autism spectrum disorder | Rare NSUN5 missense variants have been identified in ASD cohorts, suggesting a role in synaptic function. | PMID: 27824329 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 8.2 | Medium |
| Testis | 6.5 | Medium |
| Heart | 4.1 | Low |
| Liver | 3.8 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.1 | High expression |
| SH-SY5Y | 7.4 | Neuronal cell line |
| HeLa | 6.8 | Cervical carcinoma |
| K562 | 5.2 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense (start loss) | Rare | Loss of translation initiation; associated with MRT55 |
| c.472C>T (p.Arg158*) | Nonsense | Rare | Premature stop; loss of function |
| c.1045G>A (p.Gly349Arg) | Missense | Rare | Impaired methyltransferase activity |
| c.1262A>G (p.Tyr421Cys) | Missense | Rare | Reduced rRNA binding |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, start loss) cause NSUN5 deficiency, leading to intellectual disability and microcephaly.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • RNA methyltransferase activity (GO:0008173) |
| • rRNA (cytosine-C5-)-methyltransferase activity (GO:0009383) | • nucleolus (GO:0005730) |
| • rRNA processing (GO:0006364) | • methylation (GO:0032259) |
Pathways
• Ribosome biogenesis in eukaryotes (KEGG: hsa03008)
• rRNA modification in the nucleus and cytosol (Reactome: R-HSA-6790901)
Protein Summary
NSUN5 is a 456-amino acid nucleolar RNA methyltransferase that specifically catalyzes the formation of 5-methylcytosine at position 3782 of 28S rRNA. This modification is critical for proper ribosome assembly and translational fidelity. The protein contains a conserved methyltransferase domain and a nuclear localization signal. NSUN5 deficiency leads to altered ribosome function and is linked to neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSUN5 Knockout HEK293 Cell Line | EDJ-KQ14503 | Human | 55695 | Details Get a Quote |
| NSUN5 Knockout HCT 116 Cell Line | EDJ-KQ44773 | Human | 55695 | Details Get a Quote |
| NSUN5 Knockout HeLa Cell Line | EDJ-KQ44774 | Human | 55695 | Details Get a Quote |
| NSUN5 Knockout A-549 Cell Line | EDJ-KQ43518 | Human | 55695 | Details Get a Quote |
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