TSEN15
protein-codingtRNA splicing endonuclease subunit 15, the group of tRNA-splicing endonuclease subunits
Gene summary
This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]
- C1orf19
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0016759
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014874
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014874
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014874
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0014874
Submitter: G2P
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 TSEN15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052965.4. 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 | 4 | 4 | ||||
| missense | 1 | 1 | 31 | 3 | 36 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 1 | 31 | 7 | 0 | 40 |
Highest pathogenic variant AF is 0.0000013689985
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443197.1 | 5 | MANE Select | |
| Ensembl | ENSP00000493902.2 | 5 | MANE Select | |
| RefSeq | NP_001120866.1 | 4 | Standard | |
| RefSeq | NP_001287693.1 | 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 splicing, via endonucleolytic cleavage and ligation
- mRNA processing
- RNA phosphodiester bond hydrolysis, endonucleolytic
Molecular Function
- tRNA-intron endonuclease activity
- nucleic acid binding
Cellular Component
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361641
- Coding exons
- 5
- Length
- 22536
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125728
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 56 | 86.7 | 0.646 | 0.00000400 | 1097 |
| Missense (PolyPhen) | 11 | 27.752 | 0.39636 | 350 | ||
| Synonymous | 0.918 | 25 | 31.6 | 0.792 | 0.00000157 | 333 |
| Loss of Function | 1.95 | 2 | 7.91 | 0.253 | 4.00e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-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 (PubMed:15109492, PubMed:27392077). 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. 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 (PubMed:15109492). {ECO:0000269|PubMed:15109492, ECO:0000269|PubMed:27392077}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.537
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.650
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |