TSEN2 Gene
tRNA splicing endonuclease subunit 2
Gene Information Card
| Symbol | TSEN2 |
|---|---|
| Full Name | tRNA splicing endonuclease subunit 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p25.2 |
| NCBI Gene ID | 80746 ncbi.nlm.nih.gov/gene/80746 |
| Ensembl ID | ENSG00000111713 |
| UniProt ID | Q8NCE0 |
| OMIM ID | 608753 |
| HGNC ID | 28471 |
| Aliases | SEN2, SEN2L, PCH2B |
Description
The TSEN2 gene encodes the catalytic subunit 2 of the tRNA splicing endonuclease complex, which is essential for the removal of introns from precursor tRNAs. This complex cleaves pre-tRNA at the 5' and 3' splice sites, a critical step in tRNA maturation. Mutations in TSEN2 are associated with pontocerebellar hypoplasia type 2B (PCH2B), a severe neurodegenerative disorder characterized by impaired brain development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pontocerebellar hypoplasia type 2B (PCH2B) | Loss-of-function mutations in TSEN2 impair tRNA splicing, leading to defective tRNA maturation and neuronal cell death, particularly affecting the cerebellum and pons. | ClinVar, OMIM |
| Microcephaly | Disrupted tRNA processing due to TSEN2 mutations contributes to reduced brain growth and microcephaly observed in PCH2B patients. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 15.3 | Medium |
| Testis | 8.2 | Low |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.4 | Moderate expression |
| SH-SY5Y | 14.7 | Higher expression in neuronal cells |
| HeLa | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.926A>G (p.Asp309Gly) | Missense | Rare | Reduced catalytic activity of tRNA splicing endonuclease |
| c.1180C>T (p.Arg394Trp) | Missense | Rare | Impaired tRNA binding and splicing |
| c.1325_1326del (p.Glu442Glyfs*12) | Frameshift | Rare | Loss of function due to premature truncation |
Mutation functional classification
Loss of Function (LOF)
Most TSEN2 mutations are loss-of-function, reducing or abolishing tRNA splicing endonuclease activity, leading to accumulation of unspliced pre-tRNAs and cellular stress.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not established; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • tRNA-intron endonuclease activity (GO:0000214) | • tRNA-type intron splice site recognition and cleavage (GO:0000379) |
| • nucleus (GO:0005634) | • mRNA processing (GO:0006397) |
| • tRNA processing (GO:0008033) |
Pathways
• tRNA splicing (Reactome: R-HSA-6782315)
• tRNA processing (KEGG: hsa03013)
Protein Summary
TSEN2 is a 464-amino acid protein that forms the catalytic core of the tRNA splicing endonuclease complex together with TSEN15, TSEN34, and TSEN54. It contains a conserved endonuclease domain responsible for cleaving the 5' and 3' splice sites of intron-containing pre-tRNAs. The protein is predominantly nuclear and is highly expressed in brain tissues, consistent with its role in neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
