TLE4

TLE family member 4, transcriptional corepressor, the group of TLE family|WD repeat domain containing|Wnt enhanceosome complex

Basic information

Region (hg38): 9:79571772-79726882

Links

ENSG00000106829 ∙ NCBI:7091 ∙ OMIM:605132 ∙ HGNC:11840 ∙ Uniprot:Q04727 ∙ 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 TLE4 gene.

• Inborn genetic diseases (13 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLE4 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					5	5
missense			13			13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	0	5

Variants in TLE4

This is a list of pathogenic ClinVar variants found in the TLE4 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-79573700-G-T		not specified	Uncertain significance (Jun 29, 2022)
9-79652729-T-A		not specified	Uncertain significance (Apr 13, 2023)
9-79705931-G-A		not specified	Uncertain significance (Mar 23, 2023)
9-79706763-G-A		not specified	Uncertain significance (Nov 30, 2022)
9-79706810-C-T		not specified	Uncertain significance (Jan 16, 2024)
9-79708167-G-A		not specified	Uncertain significance (Jan 07, 2022)
9-79708207-A-T			Benign (Dec 31, 2019)
9-79708218-T-C		not specified	Uncertain significance (Jul 29, 2023)
9-79708613-A-G		not specified	Uncertain significance (Apr 26, 2023)
9-79708628-C-G		not specified	Uncertain significance (Sep 22, 2022)
9-79708697-G-A		not specified	Uncertain significance (Dec 27, 2022)
9-79708736-G-A		not specified	Uncertain significance (Jan 10, 2023)
9-79709677-A-G		not specified	Uncertain significance (Jul 15, 2021)
9-79718779-C-G			Benign (Apr 23, 2018)
9-79718811-A-G		not specified	Uncertain significance (Mar 02, 2023)
9-79718839-C-T			Benign (Aug 16, 2018)
9-79720148-C-T		not specified	Uncertain significance (May 24, 2023)
9-79720246-C-T			Benign (Jun 12, 2018)
9-79720259-G-A		not specified	Uncertain significance (Jun 30, 2022)
9-79722492-A-C			Benign (Aug 16, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLE4	protein_coding	protein_coding	ENST00000376552	20	154971

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000703	125722	0	3	125725	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.60	246	464	0.530	0.0000261	5061
Missense in Polyphen		70	183.65	0.38116		2074
Synonymous	-0.164	187	184	1.02	0.0000117	1537
Loss of Function	5.73	2	42.1	0.0475	0.00000214	474

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000906	0.0000906
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000329	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, and 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. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression (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: 0.147

Intolerance Scores

• loftool: 0.236
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.950
• hipred: Y
• hipred_score: 0.786
• ghis: 0.462

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tle4
• Phenotype: immune system phenotype; skeleton 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); hematopoietic system phenotype; cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;biological_process;Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway;beta-catenin-TCF complex assembly;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;nucleoplasm;transcription factor complex;beta-catenin-TCF complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;molecular_function;chromatin binding;transcription corepressor activity;protein binding;repressing transcription factor binding