TSEN2

Chr 3AR

tRNA splicing endonuclease subunit 2

Also known as: PCH2B, SEN2, SEN2L

NCBI Gene: 80746ENSG00000154743UniProt: Q8NCE0

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]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia type 2BMIM #612389
AR
386
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TSEN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 164 VUS of 386 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.00Z-score
OE missense 1.17 (1.07–1.29)
308 obs / 262.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.79 (0.55–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.07–1.29)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 20 / 25.4Missense obs/exp: 308 / 262.5Syn Z: -0.34

ClinVar Variant Classifications

386 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic17
VUS164
Likely Benign102
Benign54
Conflicting18
31
Pathogenic
17
Likely Pathogenic
164
VUS
102
Likely Benign
54
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
26
0
31
Likely Pathogenic
7
3
7
0
17
VUS
2
113
47
2
164
Likely Benign
1
6
57
38
102
Benign
1
4
41
8
54
Conflicting
—18
Total1512717848386

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

View in ClinVar →

Protein Context — Lollipop Plot

TSEN2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TSEN2-related pontocerebellar hypoplasia

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

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pontocerebellar hypoplasia type 2B

MIM #612389

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TSEN2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Management of pediatric hemolytic uremic syndrome.
Gülhan B et al.·Turk J Pediatr
2024Review
Pontocerebellar hypoplasia type 2 and TSEN2: review of the literature and two novel mutations.
Bierhals T et al.·Eur J Med Genet
2013Review
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
Biallelic TSEN2 variants causing pontocerebellar hypoplasia type 2.
Hayashi Y et al.·J Hum Genet
2025Case report
Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.
Ghasemi MR et al.·BMC Med Genomics
2024Review
[Pontocerebellar hypoplasia type 2B due to compound heterozygous variants of TSEN2 gene: A case report and literature review].
Lin X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2026Review
Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.
Namavar Y et al.·Brain
2011
Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies.
Cassandrini D et al.·Neurology
2010
Why has plasma exchange failed in TRACK syndrome? Lessons from a new variant of the atypical hemolytic uremic syndrome.
Durak C et al.·J Clin Apher
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools