TSEN2

Chr 3AR

tRNA splicing endonuclease subunit 2

Also known as: PCH2B, SEN2, SEN2L

NCBI Gene: 80746 ENSG00000154743 UniProt: Q8NCE0 OMIM: 608753

The protein is a subunit of tRNA splicing endonuclease that catalyzes the removal of introns during the first step of RNA splicing. Mutations cause pontocerebellar hypoplasia type 2B, an autosomal recessive neurodegenerative disorder. The pathogenic mechanism involves impaired tRNA processing leading to disrupted protein synthesis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 1.141 OMIM phenotype

Clinical Summary— TSEN2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 159 VUS of 369 total submissions

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GeneReview available — TSEN2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.00

OE 0.79 (0.55–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.00Z-score

OE missense 1.17 (1.07–1.29)

308 obs / 262.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.55–1.14)

0≤0.351.4

Missense OE?1.17 (1.07–1.29)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 20 / 25.4Missense obs/exp: 308 / 262.5Syn Z: -0.34

ClinVar Variant Classifications

369 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic18

VUS159

Likely Benign102

Benign54

Conflicting18

Pathogenic

Likely Pathogenic

159

VUS

102

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	1	0	0	9
Likely Pathogenic	13	4	1	0	18
VUS	3	116	37	3	159
Likely Benign	1	6	57	38	102
Benign	1	4	41	8	54
Conflicting	—				18
Total	26	131	136	49	360

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap TSEN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →