TOE1

Chr 1

target of EGR1, exonuclease

Also known as: PCH7, TOE-1, hCaf1z

NCBI Gene: 114034 ENSG00000132773 UniProt: Q96GM8

TOE1 encodes a poly(A)-specific ribonuclease that processes snRNA 3'-ends and regulates cell growth by inducing CDKN1A and TGF-beta expression. Mutations cause pontocerebellar hypoplasia type 7, an autosomal recessive disorder characterized by severe underdevelopment of the pons and cerebellum. The gene shows extreme intolerance to loss-of-function variants (pLI near 1), indicating that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.46

Clinical Summary— TOE1

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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

40 unique Pathogenic / Likely Pathogenic· 188 VUS of 387 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.07Z-score

OE missense 0.83 (0.74–0.92)

246 obs / 297.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.03 (0.74–1.46)

0≤0.351.4

Missense OE?0.83 (0.74–0.92)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 23 / 22.4Missense obs/exp: 246 / 297.8Syn Z: 0.12

ClinVar Variant Classifications

387 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic25

VUS188

Likely Benign114

Benign10

Conflicting22

Pathogenic

Likely Pathogenic

188

VUS

114

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	2	1	0	15
Likely Pathogenic	14	10	0	1	25
VUS	8	158	18	4	188
Likely Benign	4	9	48	53	114
Benign	0	4	3	3	10
Conflicting	—				22
Total	38	183	70	61	374

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap TOE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →