TSEN34
protein-codingtRNA splicing endonuclease subunit 34, the group of tRNA-splicing endonuclease subunits
Gene summary
This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]
- LENG5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012891
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012891
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0016759
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012891
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0012891
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TSEN34 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001077446.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 9 | 28 | 1 | 38 | ||
| missense | 1 | 83 | 8 | 1 | 93 | |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 2 | 97 | 36 | 2 | 138 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001070914.1 | 4 | MANE Select | |
| Ensembl | ENSP00000379671.2 | 4 | MANE Select | |
| RefSeq | NP_001269261.1 | 4 | Standard | |
| RefSeq | NP_001269262.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- tRNA processing
- Metabolism of RNA
- tRNA processing in the nucleus
- tRNA splicing
Biological Process
- tRNA-type intron splice site recognition and cleavage
- mRNA processing
- RNA phosphodiester bond hydrolysis, endonucleolytic
Molecular Function
- tRNA-intron endonuclease activity
- nucleic acid binding
- lyase activity
Cellular Component
- tRNA-intron endonuclease complex
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396383
- Coding exons
- 4
- Length
- 3797
- Individuals with no LoFs
- 124791
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 124802
- p
- 0.0000441
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.965 | 217 | 181 | 1.20 | 0.0000104 | 1938 |
| Missense (PolyPhen) | 63 | 66.509 | 0.94725 | 684 | ||
| Synonymous | -1.93 | 103 | 80.9 | 1.27 | 0.00000474 | 687 |
| Loss of Function | 2.61 | 3 | 13.3 | 0.226 | 7.38e-7 | 132 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. It probably carries the active site for 3'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'- end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. {ECO:0000269|PubMed:15109492}.;
- Disease
- DISEASE: Pontocerebellar hypoplasia 2C (PCH2C) [MIM:612390]: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration. {ECO:0000269|PubMed:18711368}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0906
Intolerance Scores
- LoFtool
- 0.430
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.710
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |