NSUN6: NOP2/Sun RNA Methyltransferase 6
A tRNA and mRNA cytosine-5 methyltransferase with emerging roles in cancer and development
Gene Information Card
| Symbol | NSUN6 |
|---|---|
| Full Name | NOP2/Sun RNA Methyltransferase 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p12.31 |
| NCBI Gene ID | 221078 ncbi.nlm.nih.gov/gene/221078 |
| Ensembl ID | ENSG00000165886 |
| UniProt ID | Q8TEA1 |
| OMIM ID | 616540 |
| HGNC ID | 32031 |
| Aliases | MSTP070, FLJ22604 |
Description
NSUN6 (NOP2/Sun RNA Methyltransferase 6) encodes a member of the NOL1/NOP2/Sun (NSUN) family of RNA methyltransferases. The enzyme catalyzes the formation of 5-methylcytosine (m5C) at specific positions in transfer RNAs (tRNA) and messenger RNAs (mRNA). NSUN6 methylates cytosine 72 (C72) in the acceptor stem of tRNAAsp, tRNAGly, tRNAHis, tRNAVal, and tRNATyr. It also methylates cytosine residues in a subset of mRNAs, influencing their stability and translation. NSUN6 is involved in RNA metabolism, cellular stress responses, and has been implicated in tumorigenesis and developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | NSUN6 downregulation correlates with poor prognosis; may regulate mRNA stability of tumor suppressors | PMID: 32015549 |
| Colorectal cancer | Reduced NSUN6 expression associated with metastasis and worse survival; potential tumor suppressor | PMID: 31409829 |
| Breast cancer | NSUN6 methylation of target mRNAs affects oncogene expression; altered expression in tumor tissues | PMID: 32789492 |
| Gastric cancer | NSUN6 low expression linked to aggressive tumor features and poor outcome | PMID: 33067267 |
| Pancreatic ductal adenocarcinoma | NSUN6 loss promotes cell proliferation and invasion via m5C modification of key transcripts | PMID: 33986539 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.2 | Medium |
| Kidney | 6.5 | Medium |
| Testis | 5.1 | Medium |
| Pancreas | 4.8 | Low |
| Lung | 3.9 | Low |
| Colon | 3.5 | Low |
| Breast | 2.1 | Low |
| Brain | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 7.8 | RNA-seq data from GTEx |
| HEK293 (embryonic kidney) | 6.2 | RNA-seq data from GTEx |
| MCF7 (breast cancer) | 2.5 | RNA-seq data from GTEx |
| A549 (lung cancer) | 3.1 | RNA-seq data from GTEx |
| K562 (leukemia) | 1.8 | RNA-seq data from GTEx |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379*) | Nonsense | <0.1% (gnomAD) | Loss of function; premature truncation |
| c.1042G>A (p.Gly348Arg) | Missense | <0.01% (gnomAD) | Unknown; predicted damaging by SIFT/PolyPhen |
| c.157G>A (p.Glu53Lys) | Missense | <0.01% (gnomAD) | Unknown; located in catalytic domain |
| c.1285_1286insA (p.Thr429Asnfs*2) | Frameshift | <0.01% (COSMIC) | Loss of function; frameshift in C-terminal region |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg379*, p.Thr429Asnfs*2) are predicted to cause loss of function by truncating the protein or inducing nonsense-mediated decay.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NSUN6.
Dominant Negative (DN)
No dominant-negative mutations have been described for NSUN6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• tRNA modification in the nucleus and cytoplasm
• mRNA stability regulation via m5C modification
Protein Summary
NSUN6 is a 456-amino acid protein (UniProt Q8TEA1) belonging to the NSUN family of RNA methyltransferases. It contains a conserved methyltransferase domain (Rossmann fold) that binds S-adenosylmethionine (SAM) as a methyl donor. NSUN6 localizes to both the nucleus and cytoplasm. It specifically methylates cytosine 72 in the acceptor stem of several tRNAs, a modification important for tRNA stability and proper folding. Additionally, NSUN6 methylates a subset of mRNAs, influencing their half-life and translation efficiency. The protein has been implicated in tumor suppression, with reduced expression observed in multiple cancer types correlating with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSUN6 Knockout HEK293 Cell Line | EDJ-KQ8795 | Human | 221078 | Details Get a Quote |
| NSUN6 Knockout A-549 Cell Line | EDJ-KQ35082 | Human | 221078 | Details Get a Quote |
| NSUN6 Knockout HeLa Cell Line | EDJ-KQ35084 | Human | 221078 | Details Get a Quote |
| NSUN6 Knockout HCT 116 Cell Line | EDJ-KQ33831 | Human | 221078 | Details Get a Quote |
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