TOE1

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

Basic information

Region (hg38): 1:45340052-45343973

Links

ENSG00000132773 ∙ NCBI:114034 ∙ OMIM:613931 ∙ HGNC:15954 ∙ Uniprot:Q96GM8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 7 (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 7 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 7 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 7 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 7	AR	General	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	Craniofacial; Endocrine; Genitourinary; Neurologic	21594990; 28092684

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOE1 gene.

• not provided (4 variants)
• Familial adenomatous polyposis 2 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	36	2	41
missense		3	79	6	4	92
nonsense	3	2				5
start loss			5			5
frameshift	2	2	1			5
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)		2				2
splice region			1	4		5
non coding	1	4	50	50	3	108
Total	6	14	140	92	9

Variants in TOE1

This is a list of pathogenic ClinVar variants found in the TOE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-45340100-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Jan 04, 2024)
1-45340116-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Mar 12, 2024)
1-45340199-G-A		not specified • Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2	Likely benign (Oct 30, 2023)
1-45340199-G-C		Familial adenomatous polyposis 2 • not specified • Hereditary cancer-predisposing syndrome	Likely benign (Jan 29, 2024)
1-45340199-G-T		Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Jan 30, 2024)
1-45340201-A-G		Hereditary cancer-predisposing syndrome	Likely benign (Jul 16, 2017)
1-45340201-A-T		Familial adenomatous polyposis 2	Likely benign (Sep 09, 2023)
1-45340203-C-A		Familial adenomatous polyposis 2	Likely benign (Oct 09, 2023)
1-45340203-C-G		Familial adenomatous polyposis 2	Likely benign (Nov 17, 2023)
1-45340203-C-T		Familial adenomatous polyposis 2	Likely benign (Apr 28, 2023)
1-45340205-C-G		Familial adenomatous polyposis 2	Likely benign (Oct 26, 2023)
1-45340206-A-C		Familial adenomatous polyposis 2	Likely benign (Mar 07, 2023)
1-45340206-A-G		Familial adenomatous polyposis 2	Likely benign (Sep 27, 2023)
1-45340208-G-A		not specified • Hereditary cancer-predisposing syndrome • Pontocerebellar hypoplasia type 7 • Familial adenomatous polyposis 2 • Carcinoma of colon	Conflicting classifications of pathogenicity (Feb 01, 2024)
1-45340208-G-C		Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2	Likely benign (Jan 25, 2024)
1-45340209-T-C		Familial adenomatous polyposis 2 • not specified	Likely benign (May 20, 2024)
1-45340209-T-G		Familial adenomatous polyposis 2 • Hereditary cancer-predisposing syndrome • not specified	Conflicting classifications of pathogenicity (Nov 27, 2023)
1-45340209-TC-T		Familial adenomatous polyposis 2	Likely benign (Feb 07, 2022)
1-45340210-C-A		Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 • not specified	Likely benign (Dec 18, 2023)
1-45340210-C-G		Familial adenomatous polyposis 2	Likely benign (Nov 16, 2022)
1-45340210-C-T		Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2	Likely benign (Aug 30, 2022)
1-45340211-C-T		Familial adenomatous polyposis 2	Likely benign (Nov 16, 2020)
1-45340212-A-C		Familial adenomatous polyposis 2	Likely benign (Oct 13, 2017)
1-45340212-A-G		Hereditary cancer-predisposing syndrome • Familial adenomatous polyposis 2 • MUTYH-related disorder	Likely benign (Aug 16, 2023)
1-45340213-G-A		Familial adenomatous polyposis 2	Uncertain significance (Nov 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOE1	protein_coding	protein_coding	ENST00000372090	8	4306

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.04e-16	0.00750	125669	0	79	125748	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	246	298	0.826	0.0000178	3349
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000620	0.000618
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000353	0.000343
Middle Eastern	0.000109	0.000109
South Asian	0.000653	0.000653
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0810
• hipred: Y
• hipred_score: 0.575
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.853

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Toe1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: toe1
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;snRNA 3'-end processing;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: nucleoplasm;nucleolus;cytoplasm;Cajal body;nuclear body;nuclear speck
• Molecular function: 3'-5'-exoribonuclease activity;DNA-binding transcription factor activity, RNA polymerase II-specific;poly(A)-specific ribonuclease activity;protein binding;snRNA binding;metal ion binding