TLE1

protein-coding

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

Gene summary

Enables DNA-binding transcription factor binding activity; identical protein binding activity; and transcription corepressor activity. Involved in negative regulation of anoikis; negative regulation of signal transduction; and regulation of gene expression. Located in cytosol and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_005077.5

Inheritance

ClinVar variants

U:108B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr9:81,583,683-81,689,547

External References & Databases

Ensembl (ENSG00000196781)

Transcript & Mutation Effects

hg38 • Region Span ~105.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

movement disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005395

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLE1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 93

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005077.5. 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			5 clinvar	3 clinvar	1 clinvar	9
missense			94 clinvar			94
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	108	3	1	112

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 141 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005077.5	RefSeq	NP_005068.2	20	MANE Select
ENST00000376499.8	Ensembl	ENSP00000365682.3	20	MANE Select
NM_001303103.2	RefSeq	NP_001290032.1	20	Standard
NM_001303104.2	RefSeq	NP_001290033.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

WNT-Ncore
Notch Signaling Pathway
Degradation of beta-catenin by the destruction complex
Signaling by WNT
Signal Transduction

Biological Process

signal transduction
multicellular organism development
animal organ morphogenesis
positive regulation of gene expression
Wnt signaling pathway

Molecular Function

transcription corepressor activity
protein binding
transcription factor binding
identical protein binding
repressing transcription factor binding

Cellular Component

nucleus
nucleoplasm
transcription factor complex
cytosol
beta-catenin-TCF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376499
Coding exons: 20
Length: 105623
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.74	305	472	0.646	0.0000285	5038
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.250

Intolerance Scores

LoFtool: 0.215
RVIS EVS: -1.57
RVIS percentile EVS: 3.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

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