TSEN34

Chr 19

tRNA splicing endonuclease subunit 34

Also known as: LENG5, PCH2C, SEN34, SEN34L

NCBI Gene: 79042 ENSG00000170892 UniProt: Q9BSV6

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.58

Clinical Summary— TSEN34

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 109 VUS of 214 total submissions

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GeneReview available — TSEN34

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.361

Z-score 2.61

OE 0.23 (0.10–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.96Z-score

OE missense 1.20 (1.07–1.34)

217 obs / 180.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.23 (0.10–0.58)

0≤0.351.4

Missense OE?1.20 (1.07–1.34)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 3 / 13.3Missense obs/exp: 217 / 180.5Syn Z: -1.93

ClinVar Variant Classifications

214 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS109

Likely Benign53

Benign31

Conflicting9

Pathogenic

Likely Pathogenic

109

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	1	0	0	0	1
VUS	2	81	17	9	109
Likely Benign	0	4	25	24	53
Benign	0	2	27	2	31
Conflicting	—				9
Total	3	88	69	35	204

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap TSEN34 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →