EIF4EBP1

Summary

EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1, HGNC:3288) is a protein-coding gene on chromosome 8p11.23, encoding Eukaryotic translation initiation factor 4E-binding protein 1 (Q13541). Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In precision oncology, EIF4EBP1 PHOSPHORYLATION confers sensitivity to Everolimus in Gastric Adenocarcinoma (CIViC Level D); 1 further curated variant–drug associations are listed below.

This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5’ end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation.

Source: NCBI Gene 1978 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• Druggable target: yes
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• MANE Select transcript: NM_004095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3288
Approved symbol	EIF4EBP1
Name	eukaryotic translation initiation factor 4E binding protein 1
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	PHAS-I, 4E-BP1
Ensembl gene	ENSG00000187840
Ensembl biotype	protein_coding
OMIM	602223
Entrez	1978

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000338825, ENST00000520657, ENST00000936832

RefSeq mRNA: 1 — MANE Select: NM_004095 NM_004095

CCDS: CCDS6100

Canonical transcript exons

ENST00000338825 — 3 exons

Exon	Start	End
ENSE00001381442	38030534	38030718
ENSE00003460623	38057081	38057260
ENSE00003505633	38059904	38060365

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 108.3449 / max 2934.6064, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88467	108.3449	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.01	gold quality
parotid gland	UBERON:0001831	98.98	gold quality
lower esophagus mucosa	UBERON:0035834	97.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.42	gold quality
saliva-secreting gland	UBERON:0001044	96.24	gold quality
esophagus mucosa	UBERON:0002469	95.90	gold quality
gastrocnemius	UBERON:0001388	95.71	gold quality
apex of heart	UBERON:0002098	95.62	gold quality
minor salivary gland	UBERON:0001830	95.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.59	gold quality
omental fat pad	UBERON:0010414	95.20	gold quality
right lobe of liver	UBERON:0001114	95.13	gold quality
peritoneum	UBERON:0002358	95.13	gold quality
pancreas	UBERON:0001264	95.01	gold quality
stromal cell of endometrium	CL:0002255	95.00	gold quality
cortical plate	UBERON:0005343	94.99	gold quality
muscle of leg	UBERON:0001383	94.92	gold quality
cartilage tissue	UBERON:0002418	94.82	gold quality
body of stomach	UBERON:0001161	94.78	gold quality
mouth mucosa	UBERON:0003729	94.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.54	gold quality
mucosa of transverse colon	UBERON:0004991	94.23	gold quality
monocyte	CL:0000576	94.08	gold quality
esophagus	UBERON:0001043	93.87	gold quality
mononuclear cell	CL:0000842	93.66	gold quality
leukocyte	CL:0000738	93.49	gold quality
diaphragm	UBERON:0001103	93.49	silver quality
right atrium auricular region	UBERON:0006631	93.29	gold quality
ganglionic eminence	UBERON:0004023	93.26	gold quality
muscle organ	UBERON:0001630	92.87	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	56.91
E-MTAB-9067	yes	20.55
E-CURD-122	yes	18.64
E-MTAB-9388	no	1293.51
E-MTAB-7303	no	456.92
E-MTAB-10290	no	309.75
E-ENAD-20	no	292.09
E-MTAB-8271	no	6.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, HIF1A, MYC, SMAD4

miRNA regulators (miRDB)

44 targeting EIF4EBP1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-7111-3P	97.80	66.75	1467

Literature-anchored findings (GeneRIF, showing 40)

• 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. (PMID:11847216)
• Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency. (PMID:11909977)
• Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E (PMID:12080086)
• hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) (PMID:12271141)
• 4E-binding protein 1 C terminus has domains that control function and phosphorylation (PMID:12588975)
• raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs. (PMID:12604610)
• data demonstrates that eukaryotic translation initiation factor 4E binding protein 1 is a new target for early growth response-1 (PMID:12618431)
• 4EBP1 is activated by the Type I IFN receptor-activated PI 3’-kinase pathway and has a role in regulating mRNA translation and induction of Type I IFN responses (PMID:12759354)
• Rheb is a mediator of 4EBP1. (PMID:12820960)
• TOR-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1 (PMID:12912989)
• Ser-64 and Ser-111 are not required for the control of PHAS-I binding to eIF4E in cells, implicating phosphorylation of the Thr sites in dissociation of the PHAS-I.eIF4E complex (PMID:14507920)
• 4EHP over-expression instigates a negative feedback loop that inhibits upstream signaling to 4E-BP1 and ribosomal protein S6 kinase 1 (S6K1) whereas the 4E-BP1-binding-deficient mutant of 4EHP(W95A) was unable to trigger this feedback loop (PMID:15094042)
• role as physiological substrates for the protein kinase activity of PI 3-kinase and suggests this activity operates in a physiological context by phosphorylating substrates other than the PI 3-kinase itself (PMID:15178440)
• These findings suggest that hyperoxia diminishes protein synthesis by increasing eIF4E phosphorylation and enhancing the affinity of 4E-BP1 for eIF4E. (PMID:15542544)
• levels of p-mTOR (Ser2481), and p-4E-BP1 (Thr70 and Ser65) dramatically increase in Alzheimer disease, and are positively significantly correlated with total tau and p-tau (PMID:16098202)
• Hypoxia inhibits protein synthesis through a 4EBP1 and EEF2 pathway controlled by mTOR and uncoupled in breast cancer cells. (PMID:16648488)
• eukaryotic translation initiation factor 4E binding protein 1(4E-BP1) overexpression is associated with prostate cancer, especially when combined with phosphatase and tensin homolog(PTEN) and mammalian target of rapamycin(mTOR) expression data (PMID:16652388)
• both ribosomal protein S6 kinase, 70kDa and 4E-BP1 pathways, regulated by TORC1, are required for cell motility (PMID:16715128)
• 4E-BP1, that binds to eukaryotic initiation factor-4E to prevent the formation of the active translation complex, dissociates from eIF4E by phosphorylation through the mammalian target of rapamycin (mTOR) in cells stimulated by amino acids. (PMID:16824195)
• AMPK activation and a reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle protein synthesis during resistance exercise. (PMID:16873412)
• In patients with ovarian carcinoma, significant expression of p-4EBP1 was associated with high-grade tumors and a poor prognosis, regardless other oncogenic alterations upstream. (PMID:16983702)
• mTOR-dependent pathways have roles in IFN signaling and 4E-BP1 and TSC1-TSC2 are key components in the generation of IFN-dependent biological responses (PMID:17114181)
• 4E-binding protein 1 has a role in progression of breast neoplasms through cell signaling (PMID:17200342)
• These results demonstrate that “pure” isoprenoids and genistein differentially impact cap-dependent translation in tumor cell lines. (PMID:17601486)
• PRAS40 acts downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1 (PMID:17604271)
• The phosphorylation of 4E-BP1 may play a dual role in the regulation of protein synthesis, both reducing the affinity of 4E-BP1 for eIF4E and promoting the conversion of 4E-BP1 to alternative, polyubiquitinated forms. (PMID:17653084)
• Phosphorylated 4E-BP1 (p-4E-BP1) expression in tumors is associated with malignant progression and an adverse prognosis regardless of the upstream oncogenic alterations. (PMID:17699757)
• Key regulator of cyclin D1 expression. (PMID:17724476)
• treatment of acute promyelocytic leukemia (APL)-derived NB4 cells with all-trans-retinoic acid results in dissociation of the translational repressor 4E-BP1 from the eukaryotic initiation factor eIF4E, and subsequent formation of eIF4G-eIF4E complexes. (PMID:18280804)
• CCL5 induced PI-3’K-, phospholipase D-, and mTOR-dependent phosphorylation and deactivation of the transcriptional repressor 4E-BP1, which resulted in its dissociation from eIF4E (PMID:18337562)
• Analysis of the regulatory motifs in EIF4EBP1 was performed. (PMID:18384376)
• SF2/ASF promotes translation initiation of bound mRNAs; this activity requires the presence of the cytoplasmic cap-binding protein eIF4E. (PMID:18439897)
• This study revealed genetic associations of SLC1A4, SQSTM1, and EIF4EBP1 with MSA. These results may lend genetic support to the hypothesis that oxidative stress is associated with the pathogenesis of MSA. (PMID:18442140)
• endocrine hormone insulin contributes to VEGF release in skin wounds through an Akt1-and 4E-BP1- mediated posttranscriptional mechanism in keratinocytes (PMID:18668138)
• chronic inactivation of 4E-BP by LRRK2 with pathogenic mutations deregulates protein translation, eventually resulting in age-dependent loss of DA neurons (PMID:18701920)
• Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival are reported. (PMID:18708753)
• These data show that, in addition to inactivation of 4E-BP1 via hyperphosphorylation, signaling through the PI3K pathway silences 4E-BP1 gene transcription. (PMID:18810319)
• Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type. (PMID:19036825)
• Expression of mTOR and 4EBP1 characterize high-grade, high-stage endometrial adenocarcinomas and might be predictive markers of a response to rapamycin. (PMID:19107520)
• PI3K signaling, therefore, plays a critical role in regulating protein production during VV infection, at least in part by controlling the abundance and activity of 4E-BP1. (PMID:19211763)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4ebp1	ENSDARG00000043608
mus_musculus	Eif4ebp1	ENSMUSG00000031490
rattus_norvegicus	Eif4ebp1	ENSRNOG00000081081
drosophila_melanogaster	Thor	FBGN0261560

Paralogs (2): EIF4EBP2 (ENSG00000148730), EIF4EBP3 (ENSG00000243056)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4E-binding protein 1 — Q13541 (reviewed: Q13541)

Alternative names: Phosphorylated heat- and acid-stable protein regulated by insulin 1

All UniProt accessions (1): Q13541

UniProt curated annotations — full annotation on UniProt →

Function. Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.

Subunit / interactions. Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E. Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.

Domain organisation. The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.

Similarity. Belongs to the eIF4E-binding protein family.

RefSeq proteins (1): NP_004086* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008606	EIF4EBP	Family

Pfam: PF05456

UniProt features (38 total): modified residue 14, mutagenesis site 9, region of interest 3, helix 3, compositionally biased region 3, short sequence motif 2, initiator methionine 1, chain 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
2JGB	X-RAY DIFFRACTION	1.7
4UED	X-RAY DIFFRACTION	1.75
3HXI	X-RAY DIFFRACTION	1.8
5NVN	X-RAY DIFFRACTION	1.9
3M94	X-RAY DIFFRACTION	2.05
1WKW	X-RAY DIFFRACTION	2.1
2V8Y	X-RAY DIFFRACTION	2.1
3HXG	X-RAY DIFFRACTION	2.1
3U7X	X-RAY DIFFRACTION	2.1
5BXV	X-RAY DIFFRACTION	2.1
1EJH	X-RAY DIFFRACTION	2.2
1EJ4	X-RAY DIFFRACTION	2.25
2V8W	X-RAY DIFFRACTION	2.3
2V8X	X-RAY DIFFRACTION	2.3
2JGC	X-RAY DIFFRACTION	2.4
3M93	X-RAY DIFFRACTION	2.9
5WBJ	X-RAY DIFFRACTION	3
8RCN	ELECTRON MICROSCOPY	3.1
6BCX	ELECTRON MICROSCOPY	3.23
9ED4	ELECTRON MICROSCOPY	3.23
8RCK	ELECTRON MICROSCOPY	3.4
5EKV	X-RAY DIFFRACTION	3.61
6BCU	ELECTRON MICROSCOPY	3.8
8RCH	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13541-F1	71.84	0.13

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 (15): 2, 37, 41, 44, 46, 50, 54, 65, 70, 77, 83, 96, 101, 112, 57

Mutagenesis-validated functional residues (9):

Position	Phenotype
37	abolishes phosphorylation by mtor and increased ubiquitination by the bcr(klhl25) complex; when associated with a-46; a-
46	abolishes phosphorylation by mtor and increased ubiquitination by the bcr(klhl25) complex; when associated with a-37; a-
57	impaired ubiquitination by the bcr(klhl25) complex.
59–60	abolishes eif4e-binding. increased ubiquitination by the bcr(klhl25) complex.
65	abolishes phosphorylation by mtor and increased ubiquitination by the bcr(klhl25) complex; when associated with a-37; a-
69	does not affect ubiquitination by the bcr(klhl25) complex.
70	abolishes phosphorylation by mtor and increased ubiquitination by the bcr(klhl25) complex; when associated with a-37; a-
105	does not affect ubiquitination by the bcr(klhl25) complex.
113	reduced interaction with rptor.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-166208	mTORC1-mediated signalling
R-HSA-72662	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-162582	Signal Transduction
R-HSA-165159	MTOR signalling
R-HSA-392499	Metabolism of proteins
R-HSA-72613	Eukaryotic Translation Initiation
R-HSA-72737	Cap-dependent Translation Initiation
R-HSA-72766	Translation

MSigDB gene sets: 285 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, ATACCTC_MIR202, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_TRANSLATIONAL_INITIATION, MODULE_16, GGGTGGRR_PAX4_03

GO Biological Process (6): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of translation (GO:0017148), TOR signaling (GO:0031929), positive regulation of mitotic cell cycle (GO:0045931), negative regulation of translational initiation (GO:0045947), regulation of translation (GO:0006417)

GO Molecular Function (4): eukaryotic initiation factor 4E binding (GO:0008190), translation repressor activity (GO:0030371), translation initiation factor binding (GO:0031369), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
MTOR signalling	1
Cap-dependent Translation Initiation	1
Signal Transduction	1
Translation	1
Eukaryotic Translation Initiation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	2
translation	2
negative regulation of translation	2
cellular anatomical structure	2
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
intracellular signal transduction	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
translational initiation	1
regulation of translational initiation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
translation initiation factor binding	1
translation regulator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4EBP1	EIF4E	P06730	999
EIF4EBP1	RPTOR	Q8N122	997
EIF4EBP1	EIF4G1	Q04637	980
EIF4EBP1	RPS6KB1	P23443	972
EIF4EBP1	MTOR	P42345	952
EIF4EBP1	RPS6	P08227	929
EIF4EBP1	MLST8	Q9BVC4	901
EIF4EBP1	AKT1	P31749	883
EIF4EBP1	TSC2	P49815	874
EIF4EBP1	EIF4A1	P04765	856
EIF4EBP1	RICTOR	Q6R327	843
EIF4EBP1	RHEB	Q15382	841
EIF4EBP1	EIF4A2	Q14240	839
EIF4EBP1	RPS6KB2	Q9UBS0	836
EIF4EBP1	TSC1	Q92574	799

IntAct

126 interactions, top by confidence:

A	B	Type	Score
EIF4EBP1	EIF4E	psi-mi:“MI:0915”(physical association)	0.980
EIF4E	EIF4EBP1	psi-mi:“MI:0915”(physical association)	0.980
EIF4EBP1	EIF4E	psi-mi:“MI:0407”(direct interaction)	0.980
EIF4E	EIF4EBP1	psi-mi:“MI:0407”(direct interaction)	0.980
	EIF4E	psi-mi:“MI:0914”(association)	0.880
EIF4E	DDX3X	psi-mi:“MI:0914”(association)	0.830
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
EIF4EBP1	RPTOR	psi-mi:“MI:0407”(direct interaction)	0.800
RPTOR	EIF4EBP1	psi-mi:“MI:0915”(physical association)	0.800

BioGRID (201): EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Affinity Capture-Western), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Affinity Capture-Western), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Two-hybrid), REL (Two-hybrid), TCF4 (Two-hybrid), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Biochemical Activity), EIF4EBP1 (Affinity Capture-MS), CHTF8 (Two-hybrid)

ESM2 similar proteins: A2AQ25, A4IGU9, A7E300, A8E4V2, B5DF41, B5DGK1, F1N4M2, O15079, O55003, O60238, O60516, Q0IHF8, Q0P5A7, Q12983, Q13541, Q14DQ1, Q1LWL8, Q3B7T9, Q3T013, Q3UN70, Q3ZCB6, Q5PR01, Q5XG16, Q5XKK7, Q5ZLN7, Q60876, Q62622, Q62739, Q63744, Q68EF0, Q68FF7, Q6AYT4, Q6PBI2, Q6PFP3, Q6ZNC4, Q7Z309, Q80U23, Q80VV3, Q8AVU0, Q8LD26

Diamond homologs: O60516, P70445, Q0P5A7, Q13541, Q13542, Q54DU8, Q60876, Q62622, Q80VV3, Q98TT6, Q9XZ56

SIGNOR signaling

64 interactions.

A	Effect	B	Mechanism
MTOR	“down-regulates activity”	EIF4EBP1	phosphorylation
CDK1	“down-regulates activity”	EIF4EBP1	phosphorylation
MAPK1	down-regulates	EIF4EBP1	phosphorylation
MAPK14	down-regulates	EIF4EBP1
EIF4EBP1	“down-regulates activity”	EIF4E	binding
GSK3B	“down-regulates activity”	EIF4EBP1	phosphorylation
CSNK1E	down-regulates	EIF4EBP1	phosphorylation
mTORC1	“down-regulates activity”	EIF4EBP1	phosphorylation
CSNK2A2	“down-regulates activity”	EIF4EBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
MTOR signalling	5	44.3×	2e-05
PIP3 activates AKT signaling	8	17.8×	4e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	16.1×	8e-04
Intracellular signaling by second messengers	5	15.2×	1e-03
Diseases of signal transduction by growth factor receptors and second messengers	6	11.4×	8e-04
Transcriptional Regulation by TP53	5	10.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	6	55.2×	6e-07
positive regulation of translation	5	29.2×	1e-04
positive regulation of cell growth	6	28.2×	2e-05
negative regulation of apoptotic process	7	6.2×	4e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1455925	NC_000008.10:g.(?37595441)(38961219_?)del	Pathogenic

SpliceAI

425 predictions. Top by Δscore:

Variant	Effect	Δscore
8:38030716:G:GT	donor_gain	1.0000
8:38030716:G:T	donor_gain	1.0000
8:38057079:A:AG	acceptor_gain	1.0000
8:38057080:G:GA	acceptor_gain	1.0000
8:38057080:G:GT	acceptor_loss	1.0000
8:38057080:GGT:G	acceptor_gain	1.0000
8:38057246:A:G	donor_gain	1.0000
8:38057256:GGGCG:G	donor_gain	1.0000
8:38057257:GGCG:G	donor_gain	1.0000
8:38057257:GGCGG:G	donor_gain	1.0000
8:38057258:GCG:G	donor_gain	1.0000
8:38057258:GCGG:G	donor_gain	1.0000
8:38057261:G:GG	donor_gain	1.0000
8:38030717:AGGT:A	donor_loss	0.9900
8:38030718:GGT:G	donor_loss	0.9900
8:38030719:GT:G	donor_loss	0.9900
8:38030720:T:G	donor_loss	0.9900
8:38057079:AG:A	acceptor_gain	0.9900
8:38057080:GG:G	acceptor_gain	0.9900
8:38057080:GGTA:G	acceptor_gain	0.9900
8:38057080:GGTAC:G	acceptor_gain	0.9900
8:38057209:G:GT	donor_gain	0.9900
8:38057245:GA:G	donor_gain	0.9900
8:38057261:G:A	donor_loss	0.9900
8:38057262:T:A	donor_loss	0.9900
8:38057263:G:GT	donor_loss	0.9900
8:38030714:GGGAG:G	donor_gain	0.9800
8:38030715:GGAGG:G	donor_gain	0.9800
8:38030865:G:GT	donor_gain	0.9800
8:38057077:CTAGG:C	acceptor_gain	0.9800

AlphaMissense

769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:38030700:T:C	F43L	0.999
8:38030702:C:A	F43L	0.999
8:38030702:C:G	F43L	0.999
8:38030703:A:C	S44R	0.999
8:38030705:C:A	S44R	0.999
8:38030705:C:G	S44R	0.999
8:38057090:T:G	I52S	0.999
8:38057095:T:G	Y54D	0.999
8:38059918:T:C	F114L	0.999
8:38059920:T:A	F114L	0.999
8:38059920:T:G	F114L	0.999
8:38030701:T:C	F43S	0.998
8:38030716:G:A	G48E	0.998
8:38057081:G:A	G49D	0.998
8:38057081:G:T	G49V	0.998
8:38057088:G:C	R51S	0.998
8:38057088:G:T	R51S	0.998
8:38057090:T:A	I52N	0.998
8:38057090:T:C	I52T	0.998
8:38057095:T:C	Y54H	0.998
8:38057102:G:C	R56P	0.998
8:38057107:T:C	F58L	0.998
8:38057109:C:A	F58L	0.998
8:38057109:C:G	F58L	0.998
8:38057111:T:C	L59P	0.998
8:38030691:G:C	G40R	0.997
8:38030692:G:A	G40D	0.997
8:38030718:G:C	G49R	0.997
8:38057093:T:A	I53N	0.997
8:38057095:T:A	Y54N	0.997

dbSNP variants (sampled 300 via entrez): RS1000005389 (8:38048874 A>G), RS1000056597 (8:38038743 T>C), RS1000279508 (8:38054640 A>T), RS1000389744 (8:38060643 C>G), RS1000485964 (8:38045387 C>CGTT), RS1000575788 (8:38033198 G>A), RS1000665025 (8:38050131 T>TGAACTCCTGACCTC), RS1000724986 (8:38059446 C>T), RS1000986673 (8:38037099 G>C), RS1001055474 (8:38037383 C>G), RS1001084168 (8:38043925 GAC>G), RS1001128592 (8:38037154 A>G), RS1001131364 (8:38031594 C>G,T), RS1001166719 (8:38053073 T>C), RS1001220528 (8:38056702 G>A)

Disease associations

OMIM: gene MIM:602223 | disease phenotypes: MIM:101600, MIM:147950

GenCC curated gene-disease

Mondo (2): Pfeiffer syndrome (MONDO:0007043), hypogonadotropic hypogonadism 2 with or without anosmia (MONDO:0007844)

Orphanet (2): Kallmann syndrome (Orphanet:478), Pfeiffer syndrome (Orphanet:710)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005863_18	Menopause (age at onset)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3351214 (SINGLE PROTEIN), CHEMBL4296088 (PROTEIN-PROTEIN INTERACTION)

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
EIF4EBP1 PHOSPHORYLATION	Everolimus	Gastric Adenocarcinoma	Sensitivity/Response	CIViC D	EID918
EIF4EBP1 PHOSPHORYLATION	MTOR Kinase Inhibitor PP242 + WYE354 + Dactolisib	Colorectal Cancer	Resistance	CIViC D	EID932

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

ChEMBL bioactivities

1789 potent at pChembl≥5 of 1805 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	IC50	0.07	nM	CHEMBL6061585
9.08	IC50	0.832	nM	CHEMBL6014814
8.98	IC50	1.05	nM	CHEMBL5829109
8.97	IC50	1.08	nM	CHEMBL6025422
8.96	IC50	1.11	nM	CHEMBL5868247
8.96	IC50	1.11	nM	CHEMBL6005726
8.88	IC50	1.32	nM	CHEMBL5942267
8.87	IC50	1.36	nM	CHEMBL6049186
8.85	IC50	1.4	nM	CHEMBL5955061
8.82	IC50	1.52	nM	CHEMBL5766874
8.80	IC50	1.57	nM	CHEMBL5872545
8.76	IC50	1.75	nM	CHEMBL5867926
8.70	IC50	2	nM	CHEMBL5749737
8.67	IC50	2.12	nM	CHEMBL5975748
8.65	IC50	2.25	nM	CHEMBL6013552
8.65	IC50	2.26	nM	CHEMBL5955775
8.63	IC50	2.33	nM	CHEMBL5865561
8.62	IC50	2.37	nM	CHEMBL5770741
8.61	IC50	2.45	nM	CHEMBL5993825
8.61	IC50	2.44	nM	CHEMBL5857755
8.61	IC50	2.44	nM	CHEMBL5837198
8.55	IC50	2.79	nM	CHEMBL5752087
8.54	IC50	2.92	nM	CHEMBL5997235
8.54	IC50	2.87	nM	CHEMBL5966247
8.54	IC50	2.87	nM	CHEMBL5823781
8.53	IC50	2.98	nM	CHEMBL6007589
8.52	IC50	3.02	nM	CHEMBL5819279
8.51	IC50	3.1	nM	CHEMBL4577429
8.51	IC50	3.12	nM	CHEMBL5902945
8.51	IC50	3.12	nM	CHEMBL5865084
8.51	IC50	3.12	nM	CHEMBL5882758
8.50	IC50	3.18	nM	CHEMBL6013609
8.50	IC50	3.15	nM	CHEMBL6060012
8.49	IC50	3.26	nM	CHEMBL5944824
8.48	IC50	3.27	nM	CHEMBL5772839
8.48	IC50	3.31	nM	CHEMBL5820229
8.48	IC50	3.32	nM	CHEMBL5999888
8.47	IC50	3.41	nM	CHEMBL6051719
8.47	IC50	3.4	nM	CHEMBL5875282
8.47	IC50	3.41	nM	CHEMBL5764132
8.46	IC50	3.51	nM	CHEMBL5999014
8.45	IC50	3.52	nM	CHEMBL5884619
8.45	IC50	3.59	nM	CHEMBL5801810
8.45	IC50	3.58	nM	CHEMBL5974991
8.45	IC50	3.58	nM	CHEMBL6010422
8.44	IC50	3.63	nM	CHEMBL5918970
8.44	IC50	3.65	nM	CHEMBL5742504
8.43	IC50	3.71	nM	CHEMBL5854914
8.42	IC50	3.8	nM	CHEMBL5873281
8.42	IC50	3.78	nM	CHEMBL6036741

PubChem BioAssay actives

8 with measured affinity, of 65 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[(2-acetamidoacetyl)amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-9-benzyl-21-[[(2R)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-12,21-dimethyl-6-(2-methylpropyl)-3-(2-methylsulfanylethyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.0031	uM
(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-2-(3-amino-3-oxopropyl)-11,20-dimethyl-5,8-bis(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carboxamide	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.0166	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[(2-acetamidoacetyl)amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2R)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.0201	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.1370	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-oxopentanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.3840	uM
(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[(2-acetamidoacetyl)amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-9-benzyl-21-[[(2R)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-3,6,12,21-tetramethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	3.5000	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-21-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]-9-benzyl-12,21-dimethyl-3,6-bis(2-methylpropyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	4.5000	uM
(2R,14R,15S)-7,14,21-trihydroxy-16-oxa-5,12,19,26-tetrazaheptacyclo[15.12.0.02,15.04,13.06,11.018,27.020,25]nonacosa-1(29),4,6(11),7,9,12,17,19,21,23,25,27-dodecaene-28-carboxylic acid	2010030: Inhibition of eIF4E-4E-BP1 (unknown origin) interaction by cat-ELCCA assay	ec50	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Sirolimus	decreases reaction, increases abundance, decreases phosphorylation, affects phosphorylation, increases phosphorylation (+6 more)	23
Resveratrol	decreases activity, decreases expression, increases expression, increases activity, decreases phosphorylation (+2 more)	8
sodium arsenite	affects cotreatment, increases abundance, increases expression, increases phosphorylation, increases reaction (+3 more)	7
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases reaction, increases response to substance, affects cotreatment, decreases phosphorylation	7
Valproic Acid	increases expression, decreases expression, affects cotreatment	7
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases phosphorylation, decreases phosphorylation, affects cotreatment, decreases reaction	6
Sorafenib	affects cotreatment, decreases phosphorylation, decreases reaction, increases phosphorylation	6
Cyclosporine	affects expression, increases expression	6
Everolimus	decreases activity, decreases reaction, increases phosphorylation, decreases phosphorylation, increases reaction (+1 more)	5
bisphenol A	affects expression, increases expression, decreases reaction	4
trichostatin A	affects cotreatment, increases expression, decreases phosphorylation	4
dactolisib	decreases phosphorylation, increases response to substance, decreases reaction, increases reaction	4
Tretinoin	decreases expression, increases reaction	4
deguelin	decreases expression, decreases phosphorylation, increases expression	3
platycodin D	decreases phosphorylation, increases reaction, affects cotreatment, decreases expression	3
temsirolimus	decreases reaction, increases phosphorylation, increases reaction, affects cotreatment, decreases phosphorylation	3
MK 2206	decreases reaction, increases phosphorylation, decreases phosphorylation, affects cotreatment	3
Wortmannin	increases abundance, decreases reaction, increases phosphorylation, increases expression, affects cotreatment	3
Cisplatin	increases phosphorylation, increases reaction, decreases phosphorylation, affects cotreatment, decreases reaction	3
Curcumin	decreases reaction, increases expression, decreases expression, decreases phosphorylation	3
Niclosamide	increases reaction, decreases phosphorylation, decreases expression, decreases reaction, increases phosphorylation (+1 more)	3
Oxygen	affects cotreatment, decreases phosphorylation, decreases reaction, increases phosphorylation, affects phosphorylation (+1 more)	3
Cadmium Chloride	increases phosphorylation, decreases reaction, increases expression	3
entinostat	increases expression, affects cotreatment	2
dorsomorphin	decreases reaction, increases phosphorylation, affects cotreatment, increases expression	2
1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one	affects binding, increases reaction, decreases phosphorylation	2
1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one	decreases phosphorylation, affects cotreatment	2
Imatinib Mesylate	decreases expression, decreases phosphorylation, increases reaction	2
Pioglitazone	increases expression, decreases phosphorylation, affects binding, decreases reaction	2
Sunitinib	affects cotreatment, decreases phosphorylation, increases expression	2

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3371381	Binding	Induction of 4E-BP1 phosphorylation at Thr37/46 in human A549 cells at 250 uM after 6 hrs by Western blotting analysis	The identification of perillyl alcohol glycosides with improved antiproliferative activity. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1QX	Abcam HeLa EIF4EBP1 KO	Cancer cell line	Female
CVCL_SL79	HAP1 EIF4EBP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07535372	Not specified	NOT_YET_RECRUITING	ASO Treatment for Syndromic Craniosynostoses