TOE1

protein-coding

target of EGR1, exonuclease, the group of PARN exonuclease family

Gene summary

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]

MANE transcript

NM_025077.4

Inheritance

ClinVar variants

P:34U:141B:59

Top phenotype

Pontocerebellar hypoplasia type 7

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr1:45,340,052-45,343,973

External References & Databases

Ensembl (ENSG00000132773)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasia type 7SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013993

Submitter: Orphanet

pontocerebellar hypoplasia type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013993

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013993

Submitter: G2P

pontocerebellar hypoplasia type 7MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013993

Submitter: Ambry Genetics

pontocerebellar hypoplasia type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013993

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Pontocerebellar hypoplasia type 7AR

Manifestation: Craniofacial; Endocrine; Genitourinary; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21594990; 28092684

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOE1 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 152

Inborn genetic diseasesTotal: 77

Pontocerebellar hypoplasia type 7Total: 38

Hereditary cancer-predisposing syndromeTotal: 25

Familial adenomatous polyposis 2Total: 22

not specifiedTotal: 13

TOE1-related disorderTotal: 13

Gastric cancerTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025077.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	6 clinvar	41 clinvar	3 clinvar	51
missense	2 clinvar	12 clinvar	121 clinvar	12 clinvar	3 clinvar	150
nonsense	4 clinvar	3 clinvar				7
start loss			5 clinvar			5
frameshift	4 clinvar	6 clinvar	4 clinvar			14
splice donor/acceptor (+/-2bp)		2 clinvar	5 clinvar			7
Total	10	24	141	53	6	234

Highest pathogenic variant AF is 0.00007870775

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025077.4	RefSeq	NP_079353.3	8	MANE Select
ENST00000372090.6	Ensembl	ENSP00000361162.5	8	MANE Select
ENST00000874144.1	Ensembl	ENSP00000544203.1	8	Standard
ENST00000874144.2	Ensembl	ENSP00000544203.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
toe1	Danio rerio	Structure: post-vent region Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

toe1

Danio rerio

Structure: post-vent region

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
snRNA 3'-end processing
RNA phosphodiester bond hydrolysis, exonucleolytic

Molecular Function

3'-5'-exoribonuclease activity
DNA-binding transcription factor activity, RNA polymerase II-specific
poly(A)-specific ribonuclease activity
protein binding
snRNA binding

Cellular Component

nucleoplasm
nucleolus
cytoplasm
Cajal body
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372090
Coding exons: 8
Length: 4306
Individuals with no LoFs: 125669
Homozygous LoFs: 0
Heterozygous LoFs: 79
Defined: 125748
p: 0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	246	298	0.826	0.0000178	3349
Missense (PolyPhen)		65	88.526	0.73425		1122
Synonymous	0.119	111	113	0.986	0.00000605	1018
Loss of Function	-0.127	23	22.4	1.03	0.00000133	250

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00035	0.00034	rare
South Asian	0.00065	0.00065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits cell growth rate and cell cycle. Induces CDKN1A expression as well as TGF-beta expression. Mediates the inhibitory growth effect of EGR1. Involved in the maturation of snRNAs and snRNA 3'-tail processing (PubMed:28092684). {ECO:0000269|PubMed:12562764, ECO:0000269|PubMed:28092684}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.874
RVIS EVS: -0.27
RVIS percentile EVS: 34.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium