TLE5

protein-coding

TLE family member 5, transcriptional modulator, the group of TLE family

Gene summary

The protein encoded by this gene is similar in sequence to the amino terminus of Drosophila enhancer of split groucho, a protein involved in neurogenesis during embryonic development. The encoded protein, which belongs to the groucho/TLE family of proteins, can function as a homooligomer or as a heteroologimer with other family members to dominantly repress the expression of other family member genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_001130.6

Inheritance

—

ClinVar variants

U:15B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr19:3,052,910-3,063,107

External References & Databases

Ensembl (ENSG00000104964)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLE5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130.6. 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			1 clinvar	1 clinvar		2
missense			8 clinvar			8
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	15	1	0	16

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130.6	RefSeq	NP_001121.2	7	MANE Select
ENST00000327141.9	Ensembl	ENSP00000317537.4	7	MANE Select
NM_198969.1	RefSeq	NP_945320.1	7	Standard
NM_198970.2	RefSeq	NP_945321.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Androgen receptor signaling pathway
Ectoderm Differentiation
Degradation of beta-catenin by the destruction complex
Signaling by WNT
Signal Transduction

Biological Process

negative regulation of transcription by RNA polymerase II
skeletal system development
multicellular organism development
animal organ morphogenesis
negative regulation of gene expression

Molecular Function

transcription corepressor activity
protein binding
repressing transcription factor binding

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221561
Coding exons: 7
Length: 10198
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.06	78	149	0.525	0.00000825	1691
Missense (PolyPhen)		11	42.036	0.26168		514
Synonymous	-1.28	85	71.3	1.19	0.00000477	533
Loss of Function	3.10	1	13.1	0.0761	5.64e-7	154

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional corepressor. Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development. {ECO:0000269|PubMed:10660609, ECO:0000269|PubMed:10748198}.;

Recessive Scores

pRec: 0.168

Intolerance Scores

LoFtool: 0.254
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.496

Gene Damage Prediction

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