TLE3

Summary

TLE3 (TLE family member 3, transcriptional corepressor, HGNC:11839) is a protein-coding gene on chromosome 15q23, encoding Transducin-like enhancer protein 3 (Q04726). Transcriptional coregulator that binds to a number of transcription factors.

This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 7090 — RefSeq curated summary.

At a glance

• GWAS associations: 54
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_001105192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11839
Approved symbol	TLE3
Name	TLE family member 3, transcriptional corepressor
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	ESG, ESG3, KIAA1547, HsT18976, GRG3
Ensembl gene	ENSG00000140332
Ensembl biotype	protein_coding
OMIM	600190
Entrez	7090

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000317509, ENST00000440567, ENST00000451782, ENST00000537387, ENST00000542329, ENST00000557815, ENST00000557907, ENST00000557919, ENST00000557984, ENST00000557997, ENST00000558201, ENST00000558379, ENST00000558939, ENST00000559048, ENST00000559191, ENST00000559574, ENST00000559608, ENST00000559826, ENST00000559929, ENST00000560525, ENST00000560589, ENST00000560939, ENST00000561453, ENST00000654081, ENST00000918356, ENST00000952208, ENST00000952209

RefSeq mRNA: 7 — MANE Select: NM_001105192 NM_001105192, NM_001282979, NM_001282980, NM_001282981, NM_001282982, NM_005078, NM_020908

CCDS: CCDS45293, CCDS45294, CCDS58375, CCDS61689, CCDS61691, CCDS61692

Canonical transcript exons

ENST00000451782 — 20 exons

Exon	Start	End
ENSE00000000284	70047790	70050204
ENSE00000942571	70096161	70096261
ENSE00000942574	70076096	70076158
ENSE00000942576	70066014	70066218
ENSE00000942577	70060530	70060649
ENSE00000942578	70059410	70059460
ENSE00000942582	70056298	70056374
ENSE00000942583	70055049	70055298
ENSE00001100423	70057459	70057658
ENSE00001607485	70074533	70074607
ENSE00001620034	70058159	70058291
ENSE00002478914	70064454	70064470
ENSE00003493833	70094532	70094576
ENSE00003531767	70095578	70095641
ENSE00003587367	70054438	70054685
ENSE00003589073	70051391	70051467
ENSE00003615281	70052374	70052524
ENSE00003651796	70058663	70058815
ENSE00003657516	70053227	70053374
ENSE00003899476	70096775	70097917

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 95.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.4287 / max 1480.2860, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150708	36.4598	1806
150706	2.2977	842
150702	2.1889	1008
150707	1.1366	667
150705	0.3036	133
150703	0.0421	17

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	95.96	gold quality
cortical plate	UBERON:0005343	94.62	gold quality
ganglionic eminence	UBERON:0004023	94.54	gold quality
lower esophagus mucosa	UBERON:0035834	94.47	gold quality
sural nerve	UBERON:0015488	94.14	gold quality
ventricular zone	UBERON:0003053	93.46	gold quality
skin of leg	UBERON:0001511	92.83	gold quality
esophagus mucosa	UBERON:0002469	92.80	gold quality
buccal mucosa cell	CL:0002336	92.75	gold quality
right testis	UBERON:0004534	92.61	gold quality
monocyte	CL:0000576	92.55	gold quality
left testis	UBERON:0004533	92.52	gold quality
skin of abdomen	UBERON:0001416	92.49	gold quality
leukocyte	CL:0000738	92.11	gold quality
mononuclear cell	CL:0000842	92.00	gold quality
mucosa of transverse colon	UBERON:0004991	91.94	gold quality
zone of skin	UBERON:0000014	91.14	gold quality
vagina	UBERON:0000996	90.83	gold quality
granulocyte	CL:0000094	90.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.66	gold quality
spleen	UBERON:0002106	90.46	gold quality
ectocervix	UBERON:0012249	90.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.22	gold quality
endocervix	UBERON:0000458	90.19	gold quality
right lung	UBERON:0002167	90.10	gold quality
testis	UBERON:0000473	90.07	gold quality
embryo	UBERON:0000922	90.00	gold quality
esophagus	UBERON:0001043	89.93	gold quality
minor salivary gland	UBERON:0001830	89.91	gold quality
upper lobe of left lung	UBERON:0008952	89.84	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.29

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RUNX1	Repression

Upstream regulators (CollecTRI, top): PROP1

miRNA regulators (miRDB)

94 targeting TLE3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 15)

• results demonstrate that different isoforms of TLE genes are commonly transcribed in human tissues and suggest that TLE3 could be involved in prostate cancer development (PMID:18273443)
• Studies suggest that TLE1 and TLE3 might also play roles independent of HESX1 by interacting with other transcription factors like PROP1. (PMID:20181723)
• A lack of TLE3 expression in cutaneous angiosarcoma may reflect differing pathogenesis. (PMID:22050093)
• High TLE3 expression predicts a favorable response to taxane containing chemotherapy regimens in ovarian carcinoma. (PMID:22194527)
• induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation (PMID:24444608)
• Increased adipose tissue (AT) TLE3 in subjects with type 2 diabetes and in AT from high fat diet and PPARgamma knockout mice suggest that TLE3 may play an adaptive regulatory role that improves AT function under decreased PPARgamma expression (PMID:25249007)
• Data indicate that microRNA miR-744 activated Wnt/beta-catenin pathway by targeting multiple negative regulators of Wnt/beta-catenin signaling, including SFRP1, GSK3beta, TLE3 and NKD1, and that NKD1 is a major functional target of miR-744. (PMID:28107193)
• Wnt signaling pathway inactivates the TLE3 co-repressor via HECT E3 ubiquitin ligase Hyd/UBR5 ubiquitination. (PMID:28689657)
• Patients with TLE3-negative tumors displayed poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed. In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients. (PMID:28859615)
• RNF6-mediated ubiquitination and degradation of TLE3 activates the Wnt/beta-catenin pathway in colorectal carcinogenesis (PMID:29374067)
• vour findings reveal a mechanistic link between TLE3 and GR-mediated resistance to AR inhibitors in human prostate cancer (PMID:31855178)
• Differential functions of TLE1 and TLE3 depending on a specific phosphorylation site. (PMID:33571907)
• Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia. (PMID:34551306)
• HHEX suppresses advanced thyroid cancer by interacting with TLE3. (PMID:37302518)
• The Wnt-pathway corepressor TLE3 interacts with the histone methyltransferase KMT1A to inhibit differentiation in Rhabdomyosarcoma. (PMID:38177411)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tle3a	ENSDARG00000002787
danio_rerio	tle3b	ENSDARG00000069006
mus_musculus	Tle3	ENSMUSG00000032280
rattus_norvegicus	Tle3	ENSRNOG00000013013
drosophila_melanogaster	gro	FBGN0001139

Paralogs (6): TLE2 (ENSG00000065717), TLE6 (ENSG00000104953), TLE5 (ENSG00000104964), TLE4 (ENSG00000106829), TLE1 (ENSG00000196781), TLE7 (ENSG00000260734)

Protein

Protein identifiers

Transducin-like enhancer protein 3 — Q04726 (reviewed: Q04726)

Alternative names: Enhancer of split groucho-like protein 3

All UniProt accessions (11): Q04726, H0YKH0, H0YKH5, H0YKN8, H0YKT5, H0YL70, H0YLI3, H0YLW9, H0YNI7, H0YNT2, Q672R2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coregulator that binds to a number of transcription factors. Acts as a regulator of adipogenesis both by acting as a corepressor of Wnt signaling and coactivator for PPARG. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. Promotes diffentiation of white adipocytes by acting as a coactivator for PPARG and preventing the association between PRDM16 and PPARG, thereby preventing browning of white adipocytes.

Subunit / interactions. Homotetramer and heterooligomer with other family members. Binds LEF1, TCF7 and TCF7L1. Binds FOXA2. Interacts with TCF7L2/TCF4. Interacts with TBX18 (via engrailed homology 1 repressor motif), leading to decreased of TBX18 transcriptional activity. Interacts with PRDM16; preventing association between PRDM16 and PPARG and browning of adipocytes.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Placenta and lung.

Post-translational modifications. Ubiquitinated by XIAP/BIRC4. This ubiquitination does not affect its stability, nuclear localization, or capacity to tetramerize but inhibits its interaction with TCF7L2/TCF4. Ubiquitinated at Lys-720 by UBR5 in response to Wnt signaling, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome.

Domain organisation. WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain.

Similarity. Belongs to the WD repeat Groucho/TLE family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q04726-1	1	yes
Q04726-2	2
Q04726-3	3
Q04726-4	4
Q04726-5	5
Q04726-6	6
Q04726-7	7

RefSeq proteins (7): NP_001098662, NP_001269908, NP_001269909, NP_001269910, NP_001269911, NP_005069, NP_065959 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR005617	Groucho/TLE_N	Domain
IPR009146	Groucho_enhance	Family
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF03920

UniProt features (64 total): modified residue 22, sequence conflict 11, repeat 7, compositionally biased region 7, splice variant 7, region of interest 6, chain 1, short sequence motif 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04726-F1	68.65	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (23): 203, 207, 211, 217, 232, 240, 245, 259, 263, 267, 275, 286, 312, 317, 319, 321, 328, 334, 413, 720 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-4641265	Repression of WNT target genes
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription

MSigDB gene sets: 348 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_416, REACTOME_SIGNALING_BY_NOTCH, HNF3ALPHA_Q6, E2F4DP1_01, GAANYNYGACNY_UNKNOWN, GOBP_WHITE_FAT_CELL_DIFFERENTIATION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_12HR_UP, STOSSI_RESPONSE_TO_ESTRADIOL, BEIER_GLIOMA_STEM_CELL_DN, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, SRF_Q5_01

GO Biological Process (9): signal transduction (GO:0007165), animal organ morphogenesis (GO:0009887), Wnt signaling pathway (GO:0016055), fat cell differentiation (GO:0045444), white fat cell differentiation (GO:0050872), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of cold-induced thermogenesis (GO:0120163), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), beta-catenin-TCF complex (GO:1990907)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	2
Degradation of beta-catenin by the destruction complex	1
ESR-mediated signaling	1
Signaling by NOTCH1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
transcription coregulator activity	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anatomical structure morphogenesis	1
animal organ development	1
cell surface receptor signaling pathway	1
cell differentiation	1
fat cell differentiation	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
negative regulation of DNA-templated transcription	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

1253 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLE3	NKX2-2	O95096	972
TLE3	HDAC1	Q13547	934
TLE3	DNMT3A	Q9Y6K1	913
TLE3	FOXA1	P55317	850
TLE3	ITGA11	Q9UKX5	829
TLE3	CORO2B	Q9UQ03	810
TLE3	NKX6-1	P78426	742
TLE3	NKX6-2	Q9C056	735
TLE3	TBX15	Q96SF7	670
TLE3	KIF23	Q02241	657
TLE3	CIB2	O75838	580
TLE3	HNF4A	P41235	577
TLE3	PRDM16	Q9HAZ2	566
TLE3	HHEX	Q03014	539
TLE3	RUNX3	Q13761	520

IntAct

103 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
TLE2	CCT6A	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
VENTX	TLE1	psi-mi:“MI:0914”(association)	0.550
HES6	TLE1	psi-mi:“MI:0914”(association)	0.550
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
SIX2	EYA2	psi-mi:“MI:0914”(association)	0.530
TLE2	TCP1	psi-mi:“MI:0914”(association)	0.530
TLE4	TLE1	psi-mi:“MI:0914”(association)	0.530
TLE3	TLE1	psi-mi:“MI:0914”(association)	0.530
TLE2	HSPA8	psi-mi:“MI:0914”(association)	0.530
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
C4A	ESR1	psi-mi:“MI:0915”(physical association)	0.400
HDAC1	TLE3	psi-mi:“MI:0915”(physical association)	0.400
lnx2b	TLE3	psi-mi:“MI:0915”(physical association)	0.400
tcf7l1a	TLE3	psi-mi:“MI:0915”(physical association)	0.400
TLE3	NOTCH1	psi-mi:“MI:0915”(physical association)	0.370
FOXA3	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXQ1	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
CUL4B	TLE1	psi-mi:“MI:0914”(association)	0.350
AUTS2	ZNF609	psi-mi:“MI:0914”(association)	0.350
CIAO1	SOX1	psi-mi:“MI:0914”(association)	0.350
rep	ABLIM1	psi-mi:“MI:0914”(association)	0.350
GSK3B	MYO1C	psi-mi:“MI:0914”(association)	0.350
EN1	RPA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (733): TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), AHCY (Co-fractionation), PPA1 (Co-fractionation), RPE (Co-fractionation), STAM (Co-fractionation), TLE3 (Co-fractionation), TLE3 (Co-fractionation), TLE3 (Co-fractionation)

ESM2 similar proteins: A1Z7A6, A8WRV1, A8WSU9, O02482, O13166, O13168, O17323, O42469, O42478, O43150, O45487, P16371, P34489, P49868, P53621, Q04724, Q04725, Q04726, Q04727, Q05B30, Q07141, Q08122, Q08882, Q09228, Q09589, Q0J7U6, Q10NY2, Q21017, Q22006, Q23175, Q23590, Q27954, Q27GK7, Q5NBT9, Q613L4, Q61J98, Q62440, Q62441, Q6AW06, Q6QM28

Diamond homologs: A0A1W2PR48, O02482, O13166, O13168, O42469, O42478, P16371, Q04724, Q04725, Q04726, Q04727, Q07141, Q08122, Q62440, Q62441, Q9H808, Q9JIT3, Q9WVB2, Q9WVB3, A1CBP8, A1DDL6, A2R3Z3, A4RJV3, A5DNK9, A6ZQL5, A6ZZZ8, A7ETB3, A7THX0, A7TNS8, A8PTE4, B3NLK7, B4GIU9, B4HN85, B4KQU8, B4P528, C8ZH19, O14170, O14435, P23232, P36130

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PHF12	“up-regulates activity”	TLE3	binding
XIAP	“up-regulates activity”	TLE3	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Repression of WNT target genes	5	44.6×	1e-05
Deactivation of the beta-catenin transactivating complex	8	23.3×	6e-07
NOTCH1 Intracellular Domain Regulates Transcription	5	14.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
urogenital system development	5	44.6×	1e-05
inner ear morphogenesis	6	16.3×	2e-04
positive regulation of epithelial cell proliferation	7	15.4×	4e-05
anatomical structure morphogenesis	12	15.1×	7e-09
epithelial cell proliferation	5	14.1×	1e-03
cell fate commitment	5	13.3×	2e-03
animal organ morphogenesis	6	10.3×	1e-03
negative regulation of canonical Wnt signaling pathway	9	9.6×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3181 predictions. Top by Δscore:

Variant	Effect	Δscore
15:70050246:G:GC	acceptor_gain	1.0000
15:70050249:C:CT	acceptor_gain	1.0000
15:70051463:CTTGC:C	acceptor_gain	1.0000
15:70051465:TGCCT:T	acceptor_loss	1.0000
15:70051468:C:CC	acceptor_gain	1.0000
15:70051468:CT:C	acceptor_loss	1.0000
15:70051469:T:A	acceptor_loss	1.0000
15:70052372:A:AC	donor_gain	1.0000
15:70052373:C:CC	donor_gain	1.0000
15:70052373:CCG:C	donor_gain	1.0000
15:70052525:C:CC	acceptor_gain	1.0000
15:70052531:G:GC	acceptor_gain	1.0000
15:70052534:G:C	acceptor_gain	1.0000
15:70054434:TCACC:T	donor_loss	1.0000
15:70054435:CA:C	donor_loss	1.0000
15:70054436:A:AT	donor_loss	1.0000
15:70054437:C:CG	donor_loss	1.0000
15:70054437:CCTGA:C	donor_gain	1.0000
15:70054681:CTGTT:C	acceptor_gain	1.0000
15:70054682:TGTT:T	acceptor_gain	1.0000
15:70054683:GTT:G	acceptor_gain	1.0000
15:70054684:TT:T	acceptor_gain	1.0000
15:70054686:C:CC	acceptor_gain	1.0000
15:70055044:CTCAC:C	donor_loss	1.0000
15:70055045:TCA:T	donor_loss	1.0000
15:70055046:CACCA:C	donor_loss	1.0000
15:70055047:A:AC	donor_gain	1.0000
15:70055047:ACCAG:A	donor_loss	1.0000
15:70055048:C:CC	donor_gain	1.0000
15:70055048:CCAGG:C	donor_gain	1.0000

AlphaMissense

5074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:70050114:A:C	Y768D	1.000
15:70050116:A:T	V767D	1.000
15:70050122:G:T	A765D	1.000
15:70050134:C:T	G761D	1.000
15:70050135:C:A	G761C	1.000
15:70050135:C:G	G761R	1.000
15:70050140:C:T	G759D	1.000
15:70050141:C:G	G759R	1.000
15:70050146:A:T	V757E	1.000
15:70050149:A:T	I756N	1.000
15:70050177:A:G	C747R	1.000
15:70050182:A:C	L745W	1.000
15:70050182:A:G	L745S	1.000
15:70050185:A:T	V744D	1.000
15:70051395:A:G	F736S	1.000
15:70051398:A:C	I735R	1.000
15:70051398:A:T	I735K	1.000
15:70051407:C:T	G732E	1.000
15:70051408:C:G	G732R	1.000
15:70051408:C:T	G732R	1.000
15:70051421:C:A	W727C	1.000
15:70051421:C:G	W727C	1.000
15:70051423:A:G	W727R	1.000
15:70051423:A:T	W727R	1.000
15:70051425:G:T	A726D	1.000
15:70051426:C:G	A726P	1.000
15:70051431:A:G	L724P	1.000
15:70051431:A:T	L724H	1.000
15:70051434:A:G	L723P	1.000
15:70051440:T:A	D721V	1.000

dbSNP variants (sampled 300 via entrez): RS1000100035 (15:70096379 T>C,G), RS1000105754 (15:70058486 A>C), RS1000190526 (15:70095207 G>A,C), RS1000201626 (15:70095407 C>A,G,T), RS1000266009 (15:70058567 T>A,C), RS1000367446 (15:70069576 C>A), RS1000427374 (15:70063228 T>C,G), RS1000478569 (15:70048704 T>C), RS1000546113 (15:70048656 A>C,G), RS1000594064 (15:70099630 G>A,C,T), RS1000639417 (15:70079619 T>G), RS1000734171 (15:70068136 T>C), RS1000819598 (15:70048426 T>C), RS1000832706 (15:70099375 C>G,T), RS1000839089 (15:70089618 T>A,C)

Disease associations

OMIM: gene MIM:600190 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

54 associations (top):

Study	Trait	p-value
GCST000817_196	Height	3.000000e-10
GCST002113_3	Pulmonary function	3.000000e-09
GCST002386_5	Cognitive function	9.000000e-06
GCST002539_76	Schizophrenia	2.000000e-08
GCST002647_110	Height	1.000000e-17
GCST003810_5	Non-response to citalopram or escitalopram and depression	1.000000e-06
GCST003983_31	Male-pattern baldness	1.000000e-09
GCST004562_113	Waist circumference adjusted for body mass index	4.000000e-07
GCST004562_148	Waist circumference adjusted for body mass index	3.000000e-08
GCST004562_60	Waist circumference adjusted for body mass index	2.000000e-06
GCST004563_17	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	6.000000e-06
GCST004563_25	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-07
GCST004563_48	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004564_79	Waist circumference adjusted for BMI in active individuals	4.000000e-06
GCST004564_80	Waist circumference adjusted for BMI in active individuals	2.000000e-06
GCST004564_81	Waist circumference adjusted for BMI in active individuals	6.000000e-07
GCST004744_21	Lung adenocarcinoma	6.000000e-07
GCST004860_102	Alcoholic chronic pancreatitis	8.000000e-06
GCST005568_1	Rheumatoid arthritis (ACPA-positive)	7.000000e-12
GCST005569_23	Rheumatoid arthritis	6.000000e-11
GCST005989_28	Serum total protein levels	2.000000e-08
GCST005990_19	Non-albumin protein levels	1.000000e-08
GCST006003_3	Triglyceride levels	2.000000e-08
GCST006048_17	Rheumatoid arthritis (ACPA-positive)	5.000000e-14
GCST006061_217	Atrial fibrillation	2.000000e-09
GCST006288_167	Heel bone mineral density	2.000000e-06
GCST006288_335	Heel bone mineral density	6.000000e-11
GCST006288_441	Heel bone mineral density	1.000000e-16
GCST006803_83	Schizophrenia	1.000000e-08
GCST006976_133	Macular thickness	3.000000e-08

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0003925	cognition
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0004530	triglyceride measurement
EFO:0009270	heel bone mineral density
EFO:0007620	volumetric bone mineral density
EFO:0004462	PR interval
EFO:0008202	L-Selectin measurement
EFO:0004327	electrocardiography
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, affects expression, affects cotreatment	2
Arsenic	affects methylation, increases abundance, increases expression	2
Ozone	affects expression, affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
cobaltous chloride	increases expression	1
nickel chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4VH	TLE3-447-D08-A01	Embryonic stem cell	Male
CVCL_D1QZ	Abcam K-562 TLE3 KO	Cancer cell line	Female
CVCL_D2MK	Abcam Raji TLE3 KO	Cancer cell line	Male
CVCL_E0R2	Ubigene HeLa TLE3 KO	Cancer cell line	Female
CVCL_TS50	HAP1 TLE3 (-) 1	Cancer cell line	Male
CVCL_TS51	HAP1 TLE3 (-) 2	Cancer cell line	Male
CVCL_WQ68	Abcam Jurkat TLE3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.