TSEN15

Chr 1AR

tRNA splicing endonuclease subunit 15

Also known as: C1orf19, PCH2F, sen15

NCBI Gene: 116461ENSG00000198860UniProt: Q8WW01

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]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 2FMIM #617026
AR
0
Active trials
26
Pathogenic / LP
87
ClinVar variants
1
Pubs (1 yr)
1.2
Missense Z
0.80
LOEUF
Clinical Summary— TSEN15
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 34 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.279
Z-score 1.95
OE 0.25 (0.10–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.65 (0.52–0.81)
56 obs / 86.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.10–0.80)
0≤0.351.4
Missense OE0.65 (0.52–0.81)
0≤0.61.4
Synonymous OE0.79
0≤1.21.6
LoF obs/exp: 2 / 7.9Missense obs/exp: 56 / 86.7Syn Z: 0.92

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS34
Likely Benign14
Benign13
24
Pathogenic
2
Likely Pathogenic
34
VUS
14
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
23
0
24
Likely Pathogenic
0
1
1
0
2
VUS
0
29
5
0
34
Likely Benign
0
2
9
3
14
Benign
0
2
11
0
13
Total03549387

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

TSEN15 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TSEN15-related pontocerebellar hypoplasia and progressive microcephaly

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.
Yang H et al.·EBioMedicine
2024
Re-evaluation and re-analysis of 152 research exomes five years after the initial report reveals clinically relevant changes in 18.
Bartolomaeus T et al.·Eur J Hum Genet
2023
A splice site mutation in the TSEN2 causes a new syndrome with craniofacial and central nervous system malformations, and atypical hemolytic uremic syndrome.
Canpolat N et al.·Clin Genet
2022
microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest.
Zhao Z et al.·RNA Biol
2015
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients