TLE4

Summary

TLE4 (TLE family member 4, transcriptional corepressor, HGNC:11840) is a protein-coding gene on chromosome 9q21.31, encoding Transducin-like enhancer protein 4 (Q04727). Transcriptional corepressor that binds to a number of transcription factors.

Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of beta-catenin-TCF complex.

Source: NCBI Gene 7091 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_007005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11840
Approved symbol	TLE4
Name	TLE family member 4, transcriptional corepressor
Location	9q21.31
Locus type	gene with protein product
Status	Approved
Aliases	E(spl), ESG, GRG4
Ensembl gene	ENSG00000106829
Ensembl biotype	protein_coding
OMIM	605132
Entrez	7091

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 16 protein_coding, 9 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000265284, ENST00000376524, ENST00000376525, ENST00000376537, ENST00000376544, ENST00000376552, ENST00000414465, ENST00000417836, ENST00000425506, ENST00000428713, ENST00000435650, ENST00000455913, ENST00000461758, ENST00000462803, ENST00000463431, ENST00000466428, ENST00000467142, ENST00000470872, ENST00000474519, ENST00000476523, ENST00000478290, ENST00000483597, ENST00000485159, ENST00000490347, ENST00000493163, ENST00000495170, ENST00000496114, ENST00000496853, ENST00000706431, ENST00000965887, ENST00000965888, ENST00000965889

RefSeq mRNA: 18 — MANE Select: NM_007005 NM_001282748, NM_001282749, NM_001282753, NM_001282760, NM_001351541, NM_001351542, NM_001351543, NM_001351546, NM_001351547, NM_001351550, NM_001351552, NM_001351556, NM_001351558, NM_001351560, NM_001351562, NM_001351563, NM_001351564, NM_007005

CCDS: CCDS43837, CCDS65069, CCDS65070, CCDS75851, CCDS94424

Canonical transcript exons

ENST00000376552 — 20 exons

Exon	Start	End
ENSE00001652753	79725037	79726882
ENSE00003462603	79722959	79723035
ENSE00003465046	79705889	79705942
ENSE00003472907	79704783	79704902
ENSE00003474816	79574873	79574936
ENSE00003493786	79718722	79718971
ENSE00003503015	79627374	79627448
ENSE00003532268	79709623	79709699
ENSE00003558842	79612656	79612718
ENSE00003570410	79721741	79721888
ENSE00003574818	79720046	79720293
ENSE00003597833	79576133	79576177
ENSE00003636496	79706747	79706899
ENSE00003649914	79573689	79573786
ENSE00003661464	79708593	79708786
ENSE00003663701	79654059	79654075
ENSE00003673548	79722451	79722601
ENSE00003786828	79652593	79652794
ENSE00003790029	79708118	79708250
ENSE00003899492	79571965	79572835

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.7208 / max 3767.2550, expressed in 1778 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97048	35.9249	1707
97047	16.8669	1644
97054	1.1843	769
97055	1.1405	652
97052	0.8946	341
97053	0.8577	592
97049	0.4563	160
97046	0.1566	43
97062	0.0863	35
97051	0.0535	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cranial nerve II	UBERON:0000941	98.00	gold quality
left testis	UBERON:0004533	97.62	gold quality
right testis	UBERON:0004534	97.62	gold quality
cortical plate	UBERON:0005343	97.57	gold quality
endothelial cell	CL:0000115	97.26	gold quality
corpus callosum	UBERON:0002336	97.18	gold quality
inferior olivary complex	UBERON:0002127	97.07	gold quality
inferior vagus X ganglion	UBERON:0005363	96.96	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.92	gold quality
CA1 field of hippocampus	UBERON:0003881	96.87	gold quality
testis	UBERON:0000473	96.78	gold quality
bone marrow cell	CL:0002092	96.29	gold quality
cervix squamous epithelium	UBERON:0006922	96.25	silver quality
lateral globus pallidus	UBERON:0002476	96.17	gold quality
medulla oblongata	UBERON:0001896	95.89	gold quality
subthalamic nucleus	UBERON:0001906	95.61	gold quality
adrenal tissue	UBERON:0018303	95.45	gold quality
choroid plexus epithelium	UBERON:0003911	95.38	gold quality
globus pallidus	UBERON:0001875	95.24	gold quality
germinal epithelium of ovary	UBERON:0001304	95.02	gold quality
medial globus pallidus	UBERON:0002477	94.94	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.92	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.66	gold quality
skin of hip	UBERON:0001554	94.64	gold quality
bone marrow	UBERON:0002371	94.36	gold quality
superior vestibular nucleus	UBERON:0007227	94.22	gold quality
substantia nigra pars compacta	UBERON:0001965	94.14	gold quality
ventral tegmental area	UBERON:0002691	94.05	gold quality
middle frontal gyrus	UBERON:0002702	94.01	gold quality
blood	UBERON:0000178	93.95	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1690.54
E-GEOD-93593	yes	210.11
E-ANND-3	yes	8.65
E-CURD-7	no	225.34

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN1B	Unknown

Upstream regulators (CollecTRI, top): FOXO1, FOXO3, HHEX, MYC

miRNA regulators (miRDB)

211 targeting TLE4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 11)

• Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors (PMID:17060451)
• Knockdown of TLE1 or TLE4 levels increased the rate of cell division of the AML1-ETO-expressing Kasumi-1 cell line, whereas forced expression of either TLE1 or TLE4 caused apoptosis and cell death. (PMID:18258796)
• germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. (PMID:19893608)
• Grg4 recruits the arginine methyltransferase PRMT5 to chromatin resulting in symmetric H4R3 dimethylation. (PMID:22169276)
• Displacing coactivators CREB-binding protein/p300 while promoting the recruitment of a corepressor, Grg4. (PMID:22927467)
• Groucho related gene Grg4 robustly activates the expression of a BMP reporter gene, as well as enhancing and sustaining the upregulation of the endogenous Id1 gene induced by BMP7. (PMID:24099773)
• PPM1B interacts with Groucho 4 and is localized to DNA in a Groucho-dependent manner, and phosphatase activity is required for transcriptional silencing. (PMID:25631048)
• the results suggested that TLE4, a potential prognostic biomarker for colorectal cancer, plays an important role in the development and progression of human colorectal cancer. (PMID:26701208)
• the loss of TLE4 confers proliferative advantage to leukemic cells, simultaneous with an upregulation of a pro- inflammatory signature mediated through aberrant increases in Wnt signaling activity (PMID:27486062)
• Genes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. (PMID:28262390)
• TLE4 regulates muscle stem cell quiescence and skeletal muscle differentiation. (PMID:35099008)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tle4	ENSMUSG00000024642
rattus_norvegicus	Tle4	ENSRNOG00000013239

Paralogs (6): TLE2 (ENSG00000065717), TLE6 (ENSG00000104953), TLE5 (ENSG00000104964), TLE3 (ENSG00000140332), TLE1 (ENSG00000196781), TLE7 (ENSG00000260734)

Protein

Protein identifiers

Transducin-like enhancer protein 4 — Q04727 (reviewed: Q04727)

Alternative names: Grg-4, Groucho-related protein 4

All UniProt accessions (13): Q04727, A0A0A0MT79, A0A994J7T6, E7EQH3, F8WAY5, H0Y5S0, H7C4E4, H7C4P7, H7C4W5, Q5JSY7, Q5JSY8, Q5JSZ1, Q5JSZ2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, 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. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression. Involved in transcriptional repression of GNRHR and enhances MSX1-mediated transcriptional repression of CGA/alpha-GSU.

Subunit / interactions. Homooligomer and heterooligomer with other family members. Interacts with PAX5. Interacts with LEF1, TCF7, TCF7L1 and TCF7L2. Interacts with ZNF703; TLE4 may mediate ZNF703 transcriptional repression. Interacts with SIX3 and SIX6. Interacts with PAX2. Interacts with TLE1.

Subcellular location. Nucleus.

Tissue specificity. In all tissues examined, mostly in brain, and muscle.

Post-translational modifications. Phosphorylated. PAX5 binding increases phosphorylation. Ubiquitinated by XIAP/BIRC4.

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 (4)

UniProt ID	Names	Canonical?
Q04727-1	1	yes
Q04727-2	2
Q04727-3	3
Q04727-4	4

RefSeq proteins (18): NP_001269677, NP_001269678, NP_001269682, NP_001269689, NP_001338470, NP_001338471, NP_001338472, NP_001338475, NP_001338476, NP_001338479, NP_001338481, NP_001338485, NP_001338487, NP_001338489, NP_001338491, NP_001338492, NP_001338493, NP_008936* (*=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 (45 total): modified residue 18, repeat 7, region of interest 7, compositionally biased region 6, splice variant 3, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04727-F1	68.88	0.43

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 (18): 208, 212, 222, 237, 245, 250, 269, 273, 281, 292, 318, 321, 323, 325, 327, 334, 340, 419

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 388 (showing top): RNGTGGGC_UNKNOWN, MYAATNNNNNNNGGC_UNKNOWN, REACTOME_SIGNALING_BY_NOTCH, AAGCAAT_MIR137, BROWNE_HCMV_INFECTION_6HR_DN, WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, TATTATA_MIR374, MODULE_182, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, HNF1_Q6

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), Wnt signaling pathway (GO:0016055), negative regulation of canonical Wnt signaling pathway (GO:0090090), cellular response to leukemia inhibitory factor (GO:1990830), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (4): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), beta-catenin-TCF complex (GO:1990907)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cell surface receptor signaling pathway	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	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
transcription coregulator activity	1
transcription factor binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLE4	PAX5	Q02548	876
TLE4	OTX2	P32243	659
TLE4	PAX2	Q02962	629
TLE4	TCF7L2	Q9NQB0	572
TLE4	RUNX1	Q01196	559
TLE4	HNF4A	P41235	549
TLE4	MEIS2	O14770	538
TLE4	CUX2	O14529	534
TLE4	GBX2	P52951	532
TLE4	FOXD3	Q9UJU5	529
TLE4	NKX6-1	P78426	522
TLE4	FEZF2	Q8TBJ5	518
TLE4	HDAC1	Q13547	516
TLE4	TBR1	Q16650	516
TLE4	CUX1	P39880	512

IntAct

66 interactions, top by confidence:

A	B	Type	Score
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
TLE2	CCT6A	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
BAG2	HGS	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
HES6	TLE4	psi-mi:“MI:0914”(association)	0.530
LYZL6	COL6A1	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
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
ATXN1		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
EN1	RPA1	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
CCT2	WDR91	psi-mi:“MI:0914”(association)	0.350
EN1	MEIS1	psi-mi:“MI:0914”(association)	0.350
FEZF1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
TLE1	TBX1	psi-mi:“MI:0914”(association)	0.350
MFAP4	PEX1	psi-mi:“MI:0914”(association)	0.350
SIX6	CLUH	psi-mi:“MI:0914”(association)	0.350
HLX	SCAF4	psi-mi:“MI:0914”(association)	0.350
CCDC183	PCNT	psi-mi:“MI:0914”(association)	0.350
TLE3	COL1A1	psi-mi:“MI:0914”(association)	0.350
ISX	DCK	psi-mi:“MI:0914”(association)	0.350
TLE4	RIPPLY3	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Two-hybrid), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), AES (Affinity Capture-MS), TLE1 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE2 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE4 (Affinity Capture-MS)

ESM2 similar proteins: A1L1N5, A4IFD2, B0R0I6, E9Q7E2, O13166, O13168, O42469, O42478, O45962, O74365, P0CF24, P23899, P27889, P35680, P49847, P49848, P58462, P83038, Q03365, Q04724, Q04727, Q05041, Q07141, Q09441, Q1LVF3, Q26622, Q2LE08, Q498D1, Q58NQ4, Q5RER5, Q5RJH6, Q5W1J5, Q62311, Q62440, Q62441, Q63801, Q68CP9, Q6P4L9, Q7ZX03, Q8MJ98

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

4 interactions.

A	Effect	B	Mechanism
TLE4	“down-regulates activity”	PAX2	binding
TLE4	“form complex”	PAX2/TLE4	binding
PHF12	“up-regulates activity”	TLE4	binding
PAX5	“down-regulates activity”	TLE4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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.

GO biological processes:

GO term	Partners	Fold	FDR
animal organ morphogenesis	6	15.1×	4e-04
anatomical structure morphogenesis	7	12.8×	3e-04
transcription by RNA polymerase II	7	6.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3561 predictions. Top by Δscore:

Variant	Effect	Δscore
9:79572836:G:GG	donor_gain	1.0000
9:79573687:A:AG	acceptor_gain	1.0000
9:79573688:G:GG	acceptor_gain	1.0000
9:79573752:G:GT	donor_gain	1.0000
9:79573782:CACAG:C	donor_loss	1.0000
9:79573783:ACAG:A	donor_loss	1.0000
9:79573784:CAGGT:C	donor_loss	1.0000
9:79573785:AG:A	donor_loss	1.0000
9:79573786:GGTAA:G	donor_loss	1.0000
9:79573787:G:T	donor_loss	1.0000
9:79573788:T:A	donor_loss	1.0000
9:79574869:ACAG:A	acceptor_loss	1.0000
9:79574871:A:AC	acceptor_loss	1.0000
9:79574871:A:AG	acceptor_gain	1.0000
9:79574871:AGTCT:A	acceptor_gain	1.0000
9:79574872:G:GA	acceptor_gain	1.0000
9:79574872:GT:G	acceptor_gain	1.0000
9:79574872:GTC:G	acceptor_gain	1.0000
9:79574872:GTCT:G	acceptor_gain	1.0000
9:79574872:GTCTG:G	acceptor_gain	1.0000
9:79576131:A:AG	acceptor_gain	1.0000
9:79576132:G:GG	acceptor_gain	1.0000
9:79576132:GT:G	acceptor_gain	1.0000
9:79576132:GTA:G	acceptor_gain	1.0000
9:79576132:GTATT:G	acceptor_gain	1.0000
9:79627372:A:AG	acceptor_gain	1.0000
9:79627373:G:GG	acceptor_gain	1.0000
9:79627446:GGG:G	donor_gain	1.0000
9:79627447:GG:G	donor_gain	1.0000
9:79627447:GGG:G	donor_gain	1.0000

AlphaMissense

5077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:79573744:G:C	R34P	1.000
9:79573758:T:C	F39L	1.000
9:79573759:T:C	F39S	1.000
9:79573760:T:A	F39L	1.000
9:79573760:T:G	F39L	1.000
9:79574875:T:C	L49P	1.000
9:79574896:T:C	L56P	1.000
9:79576143:T:C	M73T	1.000
9:79576143:T:G	M73R	1.000
9:79612675:T:C	L91P	1.000
9:79612708:T:C	L102P	1.000
9:79627395:G:C	A113P	1.000
9:79627408:C:A	A117D	1.000
9:79627432:T:C	L125P	1.000
9:79718805:C:A	P475H	1.000
9:79718852:T:C	C491R	1.000
9:79718853:G:A	C491Y	1.000
9:79718854:C:G	C491W	1.000
9:79718888:T:G	Y503D	1.000
9:79718895:G:A	G505D	1.000
9:79718903:G:C	G508R	1.000
9:79718910:T:A	V510D	1.000
9:79718918:T:A	W513R	1.000
9:79718918:T:C	W513R	1.000
9:79720064:C:A	R537S	1.000
9:79720098:T:C	L548P	1.000
9:79720104:T:A	V550D	1.000
9:79720106:G:A	G551R	1.000
9:79720106:G:C	G551R	1.000
9:79720107:G:A	G551E	1.000

dbSNP variants (sampled 300 via entrez): RS1000018449 (9:79701962 A>G), RS1000025647 (9:79652253 C>G), RS1000069629 (9:79624075 G>T), RS1000083736 (9:79617226 C>T), RS1000126914 (9:79584252 A>T), RS1000129574 (9:79679967 T>C), RS1000134340 (9:79617002 G>T), RS1000135051 (9:79658376 C>T), RS1000158374 (9:79681371 G>T), RS1000188156 (9:79699103 A>G), RS1000189561 (9:79572199 T>C), RS1000201479 (9:79600615 G>A), RS1000210733 (9:79573144 G>A,C,T), RS1000229518 (9:79726066 G>A), RS1000231999 (9:79630293 G>A)

Disease associations

OMIM: gene MIM:605132 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000468_1	Asthma (childhood onset)	7.000000e-07
GCST002352_6	Type 2 diabetes	3.000000e-08
GCST002450_6	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-06
GCST002759_16	Motion sickness	3.000000e-12
GCST003400_45	Type 2 diabetes	6.000000e-06
GCST004250_6	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	8.000000e-06
GCST004627_1	Lymphocyte count	2.000000e-13
GCST004894_148	Type 2 diabetes	2.000000e-09
GCST004894_70	Type 2 diabetes	4.000000e-06
GCST005047_70	Type 2 diabetes	3.000000e-06
GCST005047_9	Type 2 diabetes	3.000000e-07
GCST007576_140	Chronotype	5.000000e-09
GCST007847_70	Type 2 diabetes	3.000000e-06
GCST009144_13	Disease progression in age-related macular degeneration (adjusted for baseline)	8.000000e-06
GCST009379_88	Type 2 diabetes	3.000000e-14
GCST010118_173	Type 2 diabetes	6.000000e-11
GCST011494_47	Daytime nap	1.000000e-43
GCST012306_4	Bipolar disorder	3.000000e-06
GCST012307_8	Bipolar disorder x sex interaction	8.000000e-06
GCST90002388_221	Lymphocyte count	6.000000e-22
GCST90002389_350	Lymphocyte percentage of white cells	5.000000e-13
GCST90002399_78	Neutrophil percentage of white cells	5.000000e-09
GCST90002400_375	Plateletcrit	3.000000e-15
GCST90002402_61	Platelet count	3.000000e-14
GCST90026414_11	Severe insulin-resistant type 2 diabetes	8.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006928	motion sickness
EFO:0007965	response to combination chemotherapy
EFO:0004587	lymphocyte count
EFO:0008328	chronotype measurement
EFO:0008336	disease progression measurement
EFO:0007828	daytime rest measurement
EFO:0008343	sex interaction measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
methylmercuric chloride	increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Acetaminophen	affects expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	decreases expression, increases expression	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases methylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
terbufos	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
dicyclohexyl phthalate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9UC	Ubigene HEK293 TLE4 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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