TLE1

TLE family member 1, transcriptional corepressor, the group of WD repeat domain containing|Wnt enhanceosome complex|TLE family

Basic information

Region (hg38): 9:81583683-81689547

Links

ENSG00000196781

∙ NCBI:7088 ∙ OMIM:600189 ∙ HGNC:11837 ∙ Uniprot:Q04724 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

movement disorder (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLE1 gene.

not_specified (85 variants)
not_provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLE1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005077.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	1 clinvar	4
missense			84 clinvar			84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	84	3	1

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLE1	protein_coding	protein_coding	ENST00000376499	20	105623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000775	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	305	472	0.646	0.0000285	5038
Missense in Polyphen		98	205	0.47805		2230
Synonymous	-2.07	242	204	1.18	0.0000149	1512
Loss of Function	5.14	4	38.3	0.104	0.00000181	445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000642	0.0000615
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, 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. Unusual function as coactivator for ESRRG. {ECO:0000269|PubMed:10660609}.;
Pathway: WNT-Ncore;Notch Signaling Pathway;Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;wnt signaling pathway;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;Notch-mediated HES/HEY network;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Wnt Mammals;NOTCH1 Intracellular Domain Regulates Transcription;Presenilin action in Notch and Wnt signaling (Consensus)

Recessive Scores

pRec: 0.250

Intolerance Scores

loftool: 0.215
rvis_EVS: -1.57
rvis_percentile_EVS: 3.16

Haploinsufficiency Scores

pHI: 0.980
hipred: Y
hipred_score: 0.824
ghis: 0.576

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tle1
Phenotype

Gene ontology

Biological process: signal transduction;multicellular organism development;animal organ morphogenesis;positive regulation of gene expression;Wnt signaling pathway;negative regulation of Wnt signaling pathway;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of transcription, DNA-templated;negative regulation of canonical Wnt signaling pathway;beta-catenin-TCF complex assembly;negative regulation of anoikis
Cellular component: nucleus;nucleoplasm;transcription factor complex;cytosol;beta-catenin-TCF complex
Molecular function: transcription corepressor activity;protein binding;transcription factor binding;identical protein binding;repressing transcription factor binding