TSEN34

Chr 19AR

tRNA splicing endonuclease subunit 34

Also known as: LENG5, PCH2C, SEN34, SEN34L

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]

Primary Disease Associations & Inheritance

?Pontocerebellar hypoplasia type 2CMIM #612390
AR
0
Active trials
17
Pathogenic / LP
227
ClinVar variants
0
Pubs (1 yr)
-1.0
Missense Z
0.58
LOEUF
Clinical SummaryTSEN34
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 117 VUS of 227 total submissions
📖
GeneReview available — TSEN34
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.361
Z-score 2.61
OE 0.23 (0.100.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.96Z-score
OE missense 1.20 (1.071.34)
217 obs / 180.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.23 (0.100.58)
00.351.4
Missense OE1.20 (1.071.34)
00.61.4
Synonymous OE1.27
01.21.6
LoF obs/exp: 3 / 13.3Missense obs/exp: 217 / 180.5Syn Z: -1.93

ClinVar Variant Classifications

227 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS117
Likely Benign53
Benign31
Conflicting9
16
Pathogenic
1
Likely Pathogenic
117
VUS
53
Likely Benign
31
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
15
0
16
Likely Pathogenic
1
0
0
0
1
VUS
1
81
26
9
117
Likely Benign
0
4
25
24
53
Benign
0
2
27
2
31
Conflicting
9
Total2889335227

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

View in ClinVar →

TSEN34 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TSEN34-related pontocerebellar hypoplasia

limited
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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found