TSEN34

Chr 19AR

tRNA splicing endonuclease subunit 34

Also known as: LENG5, PCH2C, SEN34, SEN34L

The protein functions as a catalytic subunit of the tRNA splicing endonuclease complex, which removes introns from precursor tRNAs and is involved in pre-mRNA 3-prime end processing. Mutations cause pontocerebellar hypoplasia type 2C, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disruption of tRNA processing, which impairs protein synthesis and leads to the characteristic pontocerebellar developmental abnormalities.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.581 OMIM phenotype
Clinical SummaryTSEN34
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 117 VUS of 237 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

237 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
2
81
25
9
117
Likely Benign
0
4
25
24
53
Benign
0
2
27
2
31
Conflicting
9
Total3889235227

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

View in ClinVar →

Protein Context — Lollipop Plot

TSEN34 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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