TLE2

TLE family member 2, transcriptional corepressor, the group of TLE family|WD repeat domain containing|Wnt enhanceosome complex

Basic information

Region (hg38): 19:2997639-3047635

Links

ENSG00000065717 ∙ NCBI:7089 ∙ OMIM:601041 ∙ HGNC:11838 ∙ Uniprot:Q04725 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLE2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLE2 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				2		2
missense			44	1		45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	44	3	0

Variants in TLE2

This is a list of pathogenic ClinVar variants found in the TLE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-2997915-C-T		not specified	Uncertain significance (Sep 12, 2023)
19-2997944-C-T		not specified	Likely benign (Sep 29, 2023)
19-2997945-G-A		not specified	Uncertain significance (Sep 17, 2021)
19-3000657-C-T		Neutropenia;Lymphopenia	Likely benign (-)
19-3000683-G-A			Likely benign (Nov 01, 2022)
19-3002385-C-T		not specified	Uncertain significance (Aug 21, 2023)
19-3002415-G-A		not specified	Uncertain significance (Nov 20, 2023)
19-3002422-G-A		not specified	Uncertain significance (Mar 07, 2024)
19-3005468-C-T		not specified	Uncertain significance (Dec 09, 2023)
19-3005728-T-C		not specified	Uncertain significance (May 16, 2022)
19-3005772-C-G		not specified	Uncertain significance (Jul 20, 2021)
19-3005844-T-G		not specified	Uncertain significance (Jun 29, 2022)
19-3005856-C-A		not specified	Uncertain significance (Jun 11, 2024)
19-3005871-G-A		not specified	Uncertain significance (Feb 26, 2024)
19-3005884-T-C			Uncertain significance (Jun 30, 2022)
19-3006445-G-A		not specified	Uncertain significance (Jan 20, 2023)
19-3006476-C-T		not specified	Uncertain significance (Sep 14, 2023)
19-3006584-G-A		not specified	Uncertain significance (Jun 22, 2021)
19-3006626-C-T		not specified	Uncertain significance (May 06, 2024)
19-3006661-G-A		not specified	Uncertain significance (Sep 01, 2021)
19-3008878-C-A		not specified	Uncertain significance (Sep 22, 2023)
19-3008902-G-A		not specified	Uncertain significance (Jan 09, 2024)
19-3009552-C-T		not specified	Uncertain significance (Dec 19, 2022)
19-3009679-A-G		not specified	Uncertain significance (Feb 28, 2023)
19-3011088-C-T		Neutropenia;Lymphopenia	Likely benign (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLE2	protein_coding	protein_coding	ENST00000262953	20	49998

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.64e-7	1.00	124757	0	61	124818	0.000244

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.830	405	455	0.891	0.0000292	4718
Missense in Polyphen		125	157.82	0.79205		1604
Synonymous	-1.35	241	216	1.12	0.0000167	1504
Loss of Function	3.13	18	39.2	0.460	0.00000185	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000219	0.000216
Ashkenazi Jewish	0.00	0.00
East Asian	0.000224	0.000222
Finnish	0.0000476	0.0000464
European (Non-Finnish)	0.000346	0.000318
Middle Eastern	0.000224	0.000222
South Asian	0.000427	0.000425
Other	0.000168	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity). {ECO:0000250}.
• Pathway: Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;Repression of WNT target genes;Notch;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Deactivation of the beta-catenin transactivating complex;Wnt Canonical;Regulation of nuclear beta catenin signaling and target gene transcription;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Wnt Mammals;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.951
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.56

Haploinsufficiency Scores

• pHI: 0.423
• hipred: Y
• hipred_score: 0.595
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tle2

Gene ontology

• Biological process: signal transduction;animal organ morphogenesis;Wnt signaling pathway;negative regulation of transcription, DNA-templated;negative regulation of canonical Wnt signaling pathway;beta-catenin-TCF complex assembly
• Cellular component: extracellular space;nucleus;nucleoplasm;transcription factor complex;focal adhesion;nuclear body
• Molecular function: transcription corepressor activity;protein binding;repressing transcription factor binding