TYW3: tRNA-yW Synthesizing Protein 3 Homolog
A key enzyme in the wybutosine modification pathway of tRNA(Phe), implicated in translational fidelity and cancer.
Gene Information Card
| Symbol | TYW3 |
|---|---|
| Full Name | tRNA-yW Synthesizing Protein 3 Homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 127253 ncbi.nlm.nih.gov/gene/127253 |
| Ensembl ID | ENSG00000162613 |
| UniProt ID | Q5VZB2 |
| OMIM ID | 617862 |
| HGNC ID | 27446 |
| Aliases | C1orf171, FLJ22604, TRM12 |
Description
TYW3 encodes a protein involved in the biosynthesis of wybutosine (yW), a hypermodified nucleoside found at position 37 of eukaryotic tRNA(Phe). This modification is critical for maintaining translational fidelity by stabilizing codon-anticodon interactions. TYW3 catalyzes the methylation of N1-methylguanine to form N1,N2-dimethylguanine in the wybutosine pathway. The gene is conserved across eukaryotes and is expressed in a variety of tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered TYW3 expression may disrupt tRNA modification, leading to translational errors and oncogenic transformation. | COSMIC database reports somatic mutations in TYW3 across multiple cancer types. |
| Neurodevelopmental disorders | Potential link due to impaired translational fidelity affecting neuronal protein synthesis. | Inferred from functional studies; no direct ClinVar entries as of 2025. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
| Heart | 5.4 | Low |
| Kidney | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney cells |
| HeLa | 7.8 | Cervical cancer cells |
| K562 | 6.5 | Leukemia cells |
| HepG2 | 5.9 | Liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.287G>A (p.Arg96His) | Missense | 0.02% (gnomAD) | Unknown functional impact |
| c.412C>T (p.Pro138Ser) | Missense | 0.01% (gnomAD) | Predicted benign |
| c.523_524insA (p.Thr175Asnfs*3) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations likely abolish enzymatic activity, impairing wybutosine synthesis.
Gain of Function (GOF)
No evidence of gain-of-function mutations reported.
Dominant Negative (DN)
No known dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • methyltransferase activity (GO:0008168) |
| • tRNA processing (GO:0008033) | • cytoplasm (GO:0005737) |
Pathways
• Wybutosine biosynthesis (R-HSA-6782315)
Protein Summary
TYW3 is a 299-amino acid protein localized to the cytoplasm. It belongs to the methyltransferase superfamily and specifically methylates guanine at position 37 of tRNA(Phe). The protein contains an S-adenosylmethionine (SAM) binding domain essential for its catalytic activity. Structural studies indicate a Rossmann-like fold typical of class I methyltransferases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TYW3 Knockout HEK293 Cell Line | EDJ-KQ9022 | Human | 127253 | Details Get a Quote |
| TYW3 Knockout A-549 Cell Line | EDJ-KQ35459 | Human | 127253 | Details Get a Quote |
| TYW3 Knockout HCT 116 Cell Line | EDJ-KQ35460 | Human | 127253 | Details Get a Quote |
| TYW3 Knockout HeLa Cell Line | EDJ-KQ35461 | Human | 127253 | Details Get a Quote |
