TOE1

Chr 1AR

target of EGR1, exonuclease

Also known as: PCH7, TOE-1, hCaf1z

NCBI Gene: 114034ENSG00000132773UniProt: Q96GM8

Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 7MIM #614969
AR
385
ClinVar variants
45
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TOE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 196 VUS of 385 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.
1.46LOEUF
pLI 0.000
Z-score -0.13
OE 1.03 (0.74–1.46)
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.
1.07Z-score
OE missense 0.83 (0.74–0.92)
246 obs / 297.8 exp
Tolerant

Mild missense constraint

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.1.03 (0.74–1.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.74–0.92)
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.0.99
0≤1.21.6
LoF obs/exp: 23 / 22.4Missense obs/exp: 246 / 297.8Syn Z: 0.12

ClinVar Variant Classifications

385 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic26
VUS196
Likely Benign113
Benign10
Conflicting21
19
Pathogenic
26
Likely Pathogenic
196
VUS
113
Likely Benign
10
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
9
0
19
Likely Pathogenic
8
9
8
1
26
VUS
7
154
31
4
196
Likely Benign
4
9
48
52
113
Benign
0
4
3
3
10
Conflicting
—21
Total271789960385

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

View in ClinVar →

Protein Context — Lollipop Plot

TOE1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TOE1-related pontocerebellar hypoplasia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TARGET OF EGR1; TOE1
MIM #613931 · *

Pontocerebellar hypoplasia, type 7

MIM #614969

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic and prenatal diagnosis of a Chinese pedigree with pathogenic TOE1 variants causing pontocerebellar hypoplasia type 7.
Guo H et al.·J Matern Fetal Neonatal Med
2023
Transcriptomic analysis reveals the potential role of TOE1 in hepatocellular carcinoma.
Ao JY et al.·Sci Rep
2025
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
Novel compound heterozygous variant of TOE1 results in a mild type of pontocerebellar hypoplasia type 7: an expansion of the clinical phenotype.
Chen H et al.·Neurogenetics
2022Case report
Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7.
Kuroda Y et al.·J Hum Genet
2024Case report
Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.
Bilge S et al.·Ital J Pediatr
2022
Genetic predisposition to differentiated thyroid cancer in the Polish population.
Borowczyk M et al.·Pol Arch Intern Med
2024
Exome Sequencing Identified Susceptible Genes for High Residual Risks in Early-Onset Coronary Atherosclerotic Disease.
Wu R et al.·Clin Cardiol
2024
Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.
Wu ZF et al.·Am J Med Genet A
2024Case report
Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study.
Nuovo S et al.·J Med Genet
2022
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