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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TLE5
TLE family member 5, transcriptional modulator
Chromosome 19 · 19p13.3
NCBI Gene: 166Ensembl: ENSG00000104964.16HGNC: HGNC:307UniProt: Q08117
89PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription corepressor activityprotein bindingnegative regulation of transcription by RNA polymerase IIpositive regulation of anoikisatrial fibrillationatherosclerosismouth diseaseshort stature due to GHSR deficiency
✦AI Summary

TLE5 is a transcriptional corepressor protein that functions as a negative regulator of gene expression and signaling pathways. While the provided abstracts do not contain direct studies of TLE5, they provide insights into closely related family members. TLE5 belongs to the Groucho/TLE family of co-repressor proteins, which are recruited by transcription factors to inhibit productive transcription 1. Related family member AES (amino-terminal enhancer of split) demonstrates similar corepressor functions, interacting with TCF4 to downregulate Wnt signaling in human cells and zebrafish embryos 2. AES acts as a tumor and metastasis suppressor in colorectal cancer, where its degradation by CK1δ/ε kinases leads to enhanced tumorigenesis and metastasis 3. The protein functions through specific protein-protein interactions, as demonstrated by AES binding to TCF4 via a conserved LVPQ motif 2. In pituitary development, AES deficiency causes growth abnormalities, indicating essential roles in developmental processes 4. Based on family member functions and UniProt annotations, TLE5 likely serves as a dominant transcriptional repressor that inhibits NF-κB signaling and may be important for maintaining differentiated cell states, though specific experimental validation of TLE5 function requires further investigation.

Sources cited
1
Groucho/TLE family proteins function as co-repressors recruited by transcription factors to inhibit transcription
PMID: 25603281
2
Related family member AES interacts with TCF4 to downregulate Wnt signaling
PMID: 23840876
3
AES acts as tumor and metastasis suppressor in colorectal cancer
PMID: 33754069
4
AES deficiency causes pituitary growth abnormalities
PMID: 12907761
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.47Moderate
atherosclerosisOpen Targets
0.27Weak
mouth diseaseOpen Targets
0.13Weak
short stature due to GHSR deficiencyOpen Targets
0.06Suggestive
short stature due to partial GHR deficiencyOpen Targets
0.06Suggestive
Non-acquired isolated growth hormone deficiencyOpen Targets
0.05Suggestive
Pituitary Gland AdenomaOpen Targets
0.05Suggestive
non-acquired combined pituitary hormone deficiency with spine abnormalitiesOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
isolated growth hormone deficiency, type 4Open Targets
0.05Suggestive
isolated growth hormone deficiency type IIOpen Targets
0.04Suggestive
pituitary adenoma 5, multiple typesOpen Targets
0.04Suggestive
panhypopituitarism, X-linkedOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
pituitary adenocarcinomaOpen Targets
0.04Suggestive
isolated growth hormone deficiency, type 5Open Targets
0.04Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
acromegalyOpen Targets
0.04Suggestive
growth hormone-secreting pituitary adenomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TLE3Protein interaction93%TLE1Protein interaction92%TLE4Protein interaction91%TLE2Protein interaction86%RIPPLY1Protein interaction83%VENTXProtein interaction80%
Tissue Expression6 tissues
Brain
100%
Heart
75%
Lung
61%
Ovary
56%
Liver
51%
Bone Marrow
21%
Gene Interaction Network
Click a node to explore
TLE5TLE3TLE1TLE4TLE2RIPPLY1VENTX
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q08117
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.63LoF Tolerant
pLIⓘ
0.79Intermediate
Observed/Expected LoF0.32 [0.17–0.63]
RankingsWhere TLE5 stands among ~20K protein-coding genes
  • #5,385of 20,598
    Most Researched89
  • #4,462of 17,882
    Most Constrained (LOEUF)0.63 · top quartile
Genes detectedTLE5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 40574274
J Dent Res · 2025
1.00
2
Human ESP1/CRP2, a member of the LIM domain protein family: characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3.
PMID: 8824798
Genomics · 1996
0.90
3
Genomic organization and chromosome localization to band 19p13.3 of the human AES gene: gene product exhibits strong similarity to the N-terminal domain of Drosophila enhancer of Split Groucho protein.
PMID: 9809752
DNA Cell Biol · 1998
0.80
4
The CK1δ/ε-AES axis regulates tumorigenesis and metastasis in colorectal cancer.
PMID: 33754069
Theranostics · 2021
0.70
5
GRG5/AES interacts with T-cell factor 4 (TCF4) and downregulates Wnt signaling in human cells and zebrafish embryos.
PMID: 23840876
PLoS One · 2013
0.60