EIF3E

Summary

EIF3E (eukaryotic translation initiation factor 3 subunit E, HGNC:3277) is a protein-coding gene on chromosome 8q23.1, encoding Eukaryotic translation initiation factor 3 subunit E (P60228). Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Enables RNA binding activity and cadherin binding activity. Contributes to translation initiation factor activity. Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; positive regulation of translation; and translational initiation. Located in PML body and cytosol. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 3646 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 50 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3277
Approved symbol	EIF3E
Name	eukaryotic translation initiation factor 3 subunit E
Location	8q23.1
Locus type	gene with protein product
Status	Approved
Aliases	eIF3-p48
Ensembl gene	ENSG00000104408
Ensembl biotype	protein_coding
OMIM	602210
Entrez	3646

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 30 protein_coding, 11 retained_intron, 10 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay

ENST00000220849, ENST00000518100, ENST00000518345, ENST00000518442, ENST00000518634, ENST00000519030, ENST00000519413, ENST00000519517, ENST00000519627, ENST00000521297, ENST00000521440, ENST00000521614, ENST00000522088, ENST00000522352, ENST00000522445, ENST00000522887, ENST00000523646, ENST00000523674, ENST00000676487, ENST00000676530, ENST00000676548, ENST00000676642, ENST00000676663, ENST00000676698, ENST00000676706, ENST00000676892, ENST00000676931, ENST00000677040, ENST00000677084, ENST00000677215, ENST00000677272, ENST00000677317, ENST00000677409, ENST00000677447, ENST00000677458, ENST00000677501, ENST00000677524, ENST00000677590, ENST00000677614, ENST00000677674, ENST00000677696, ENST00000677746, ENST00000677965, ENST00000678004, ENST00000678023, ENST00000678042, ENST00000678243, ENST00000678334, ENST00000678472, ENST00000678773, ENST00000678797, ENST00000678881, ENST00000678887, ENST00000678901, ENST00000678937, ENST00000679009, ENST00000679198, ENST00000921171

RefSeq mRNA: 1 — MANE Select: NM_001568 NM_001568

CCDS: CCDS6308

Canonical transcript exons

ENST00000220849 — 13 exons

Exon	Start	End
ENSE00003485318	108202983	108203117
ENSE00003542024	108236161	108236203
ENSE00003561022	108217334	108217460
ENSE00003565895	108229070	108229195
ENSE00003596551	108203401	108203503
ENSE00003602504	108239958	108240075
ENSE00003604637	108234998	108235102
ENSE00003610725	108241799	108241913
ENSE00003660520	108216412	108216513
ENSE00003671921	108248613	108248717
ENSE00003681490	108228267	108228391
ENSE00003788941	108214607	108214716
ENSE00003891060	108201216	108201923

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 272.7843 / max 4424.4100, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94395	271.1495	1826
94401	0.7101	238
94400	0.3390	161
94394	0.3346	146
94399	0.2511	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.60	gold quality
tendon of biceps brachii	UBERON:0008188	99.60	gold quality
parietal pleura	UBERON:0002400	99.59	gold quality
cortical plate	UBERON:0005343	99.59	gold quality
tendon	UBERON:0000043	99.58	gold quality
ovary	UBERON:0000992	99.58	gold quality
germinal epithelium of ovary	UBERON:0001304	99.56	gold quality
left ovary	UBERON:0002119	99.56	gold quality
ganglionic eminence	UBERON:0004023	99.55	gold quality
upper leg skin	UBERON:0004262	99.55	gold quality
skin of hip	UBERON:0001554	99.54	gold quality
embryo	UBERON:0000922	99.53	gold quality
pleura	UBERON:0000977	99.52	gold quality
body of pancreas	UBERON:0001150	99.52	gold quality
parotid gland	UBERON:0001831	99.51	gold quality
mammary duct	UBERON:0001765	99.47	gold quality
right ovary	UBERON:0002118	99.46	gold quality
ventricular zone	UBERON:0003053	99.46	gold quality
endocervix	UBERON:0000458	99.45	gold quality
endometrium	UBERON:0001295	99.45	gold quality
caput epididymis	UBERON:0004358	99.44	gold quality
lymph node	UBERON:0000029	99.43	gold quality
colonic epithelium	UBERON:0000397	99.41	gold quality
seminal vesicle	UBERON:0000998	99.41	gold quality
body of uterus	UBERON:0009853	99.41	gold quality
visceral pleura	UBERON:0002401	99.38	gold quality
mammary gland	UBERON:0001911	99.37	gold quality
hair follicle	UBERON:0002073	99.37	gold quality
epithelium of mammary gland	UBERON:0003244	99.37	gold quality
thoracic mammary gland	UBERON:0005200	99.37	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	2020.00
E-MTAB-8142	yes	122.61
E-MTAB-9467	yes	67.18
E-HCAD-11	yes	42.63
E-CURD-46	yes	40.52
E-CURD-88	yes	34.18
E-HCAD-1	yes	22.93
E-GEOD-125970	yes	19.98
E-MTAB-10042	yes	14.07
E-CURD-112	yes	6.07
E-CURD-122	yes	4.72
E-GEOD-124472	no	2360.34
E-MTAB-10432	no	1710.91
E-HCAD-6	no	1362.31
E-GEOD-124858	no	1257.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1

miRNA regulators (miRDB)

10 targeting EIF3E, 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-4282	99.99	75.36	6408
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-6879-3P	93.93	64.00	759

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 28)

• Int-6 protein can bind the three complexes /eIF3, COP9 signalosome and 26S proteasome/, possibly exerting a regulatory activity in both protein translation and degradation (PMID:12220626)
• EIF3e/INT6 is localized in part to the nucleus, while other eIF3 components are cytoplasmic. Primary human fibroblasts showed reduced nuclear INT6 staining in early S phase. (PMID:15030549)
• Reducing Int-6 expression by RNA interference in HeLa cells markedly alters mitosis progression and defects in spindle formation, chromosome segregation and cytokinesis are observed. (PMID:15558017)
• Results suggest that Int6 expression, evaluated by quantitative real-time PCR, may represent a new prognostic factor in patients with stage I non-small cell lung cancers. (PMID:15867213)
• eIF3e binds to eIF4G during the process of cap-dependent translation initiation (PMID:16766523)
• INT6 stabilizes chromatin-bound MCM7 and alteration of this effect is associated with replication deficiency. (PMID:17310990)
• INT6 knockdown by RNA interference strongly inhibits nonsense-mediated messenger RNA decay (NMD), which triggers degradation of mRNAs with premature stop codons. (PMID:17468741)
• data suggest that eIF3e has a positive role in breast cancer progression. It regulates the translation, and in some cases abundance, of mRNAs involved in key aspects of cancer cell biology (PMID:20453879)
• Int6 depletion blocks ubiquitin-dependent proteolysis by decreasing both ubiquitin levels and the assembly of functional proteasome machinery, leading to accumulation of oncoproteins, such as SRC3. (PMID:20890303)
• findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 (PMID:22508697)
• INT6 and MIF4GD were observed to colocalize in cytoplasmic foci. It was concluded that INT6, by establishing interactions with MIF4GD and SLBP, plays an important role in translation of poly(A) minus histone mRNAs. (PMID:22532700)
• HTLV-1Tax binds both INT6 and UPF1. The analysis of Tax mutants indicated that the Tax-INT6 association is necessary for nonsense-mediated mRNA decay inhibition, and data suggest that Tax sequesters INT6 out of reach from UPF1. (PMID:22553336)
• novel role of eIF3e/Int6 in the regulation of EMT in breast epithelial cells (PMID:22907435)
• Our findings indicate that Int6 act as a hypoxia-independent master switch of angiogenesis in neuronal cells (PMID:22960363)
• IL-6 and IL-8 are HIF2alpha controlled cytokines for angiogenesis particularly in endothelial cells. (PMID:23478175)
• eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome. (PMID:24092755)
• Int6/eIF3e is essential for proliferation and survival of human glioblastoma cells. (PMID:24481065)
• 40S ribosome loading imparts a phosphorylation mark on the cap-binding eIF4F complex that regulates selective mRNA translation and is synchronized by a specific eIF3 subunit (PMID:24736843)
• High eIF3e expression may contribute to tumor progression and predict poor prognosis in colon cancer. (PMID:25400724)
• eIF3e is an angiogenesis suppressor. Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through stabilization of hypoxia-inducible factor 2alpha activity. (PMID:25758454)
• A transcript-specific eIF3 complex mediates global translational control of energy metabolism. (PMID:27477275)
• INT6 protects against breast cancer by showing how it functions in DSB repair, with potential clinical implications for cancer therapy. (PMID:27550454)
• These data suggest that eIF3e downregulation may be involved in epithelial-mesenchymal transition in endometriosis, possibly through preferential translation of Snail. (PMID:28438065)
• Data suggest that decreased eukaryotic translation initiation factor 3 subunit e expression may pave way for epithelial-mesenchymal transition in the development of adenomyosis through activating the TGF-beta1 signaling pathway. (PMID:29871559)
• An EIF3E-RSPO2 fusion was detected in three colorectal serrated polyps (PMID:30916365)
• eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health. (PMID:32589965)
• MiR-335-3p inhibits cell proliferation and induces cell cycle arrest and apoptosis in acute myeloid leukemia by targeting EIF3E. (PMID:34191006)
• Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma. (PMID:38124661)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3eb	ENSDARG00000002549
danio_rerio	eif3ea	ENSDARG00000090697
mus_musculus	Eif3e	ENSMUSG00000022336
rattus_norvegicus	Eif3el1	ENSRNOG00000027690
rattus_norvegicus	Eif3el1	ENSRNOG00000060288
drosophila_melanogaster	eIF3e	FBGN0025582
caenorhabditis_elegans	eif-3.E	WBGENE00001228

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit E — P60228 (reviewed: P60228)

Alternative names: Eukaryotic translation initiation factor 3 subunit 6, Viral integration site protein INT-6 homolog, eIF-3 p48

All UniProt accessions (26): P60228, A0A161SXE1, A0A7I2V2H9, A0A7I2V2Q9, A0A7I2V2S9, A0A7I2V2W0, A0A7I2V3I0, A0A7I2V3I2, A0A7I2V3S3, A0A7I2V3W9, A0A7I2V429, A0A7I2V4B4, A0A7I2V4G3, A0A7I2V570, A0A7I2V5K7, A0A7I2V5P9, A0A7I2V5Z6, B3KW56, E5RGA2, E5RHS5, E5RII3, E5RIP5, E5RJ25, H0YAW4, H0YBP5, H0YBR5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway. May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins.

Subunit / interactions. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with COPS3, COPS6, COPS7 (COPS7A or COPS7B), EIF4G1, EPAS1, MCM7, NCBP1, PSMC6, TRIM27 and UPF2. Interacts with the HTLV-1 protein Tax-1. Interacts with IFIT1 and IFIT2. Interacts with BZW2/5MP1.

Subcellular location. Cytoplasm. Nucleus. PML body.

Tissue specificity. Ubiquitously expressed. Expressed at highest levels in appendix, lymph, pancreas, skeletal muscle, spleen and thymus.

Similarity. Belongs to the eIF-3 subunit E family.

RefSeq proteins (1): NP_001559* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR016650	eIF3e	Family
IPR019010	eIF3e_N	Domain
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF01399, PF09440, PF21357

UniProt features (63 total): helix 24, turn 17, strand 9, modified residue 5, region of interest 3, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6ZON	ELECTRON MICROSCOPY	3
9KZU	ELECTRON MICROSCOPY	3
8PJ4	ELECTRON MICROSCOPY	3.2
9KN5	ELECTRON MICROSCOPY	3.2
9KRP	ELECTRON MICROSCOPY	3.2
6YBD	ELECTRON MICROSCOPY	3.3
9KKF	ELECTRON MICROSCOPY	3.3
9KN6	ELECTRON MICROSCOPY	3.3
9KZX	ELECTRON MICROSCOPY	3.3
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
8RG0	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
8XXN	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
7QP7	ELECTRON MICROSCOPY	3.7
8PJ3	ELECTRON MICROSCOPY	3.7
6ZVJ	ELECTRON MICROSCOPY	3.8
9BLN	ELECTRON MICROSCOPY	3.9
7QP6	ELECTRON MICROSCOPY	4.7
6FEC	ELECTRON MICROSCOPY	6.3
3J8B	ELECTRON MICROSCOPY	9.3
3J8C	ELECTRON MICROSCOPY	11.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60228-F1	64.89	0.02

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 (5): 445, 2, 399, 439, 442

Mutagenesis-validated functional residues (1):

Position	Phenotype
312	promotes nuclear accumulation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit

MSigDB gene sets: 262 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_CYTOPLASMIC_TRANSLATION, TGCGCANK_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_151, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION

GO Biological Process (8): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), positive regulation of translation (GO:0045727), negative regulation of translational initiation (GO:0045947), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (4): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (14): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), postsynaptic density (GO:0014069), membrane (GO:0016020), eukaryotic 43S preinitiation complex (GO:0016282), PML body (GO:0016605), eukaryotic 48S preinitiation complex (GO:0033290), extracellular exosome (GO:0070062), eukaryotic translation initiation factor 3 complex, eIF3e (GO:0071540), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Eukaryotic Translation Initiation	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	5
cellular anatomical structure	5
translation	2
regulation of translation	2
cytoplasm	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
nuclear-transcribed mRNA catabolic process	1
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
formation of translation initiation ternary complex	1
metabolic process	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
regulation of translational initiation	1
negative regulation of translation	1
cytoplasmic translation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
translation factor activity	1
cell adhesion molecule binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
protein-containing complex	1
asymmetric synapse	1
postsynaptic specialization	1
nuclear body	1
extracellular vesicle	1
eukaryotic translation initiation factor 3 complex	1
cellular_component	1

Protein interactions and networks

STRING

2482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3E	EIF3D	O15371	995
EIF3E	EIF3C	Q99613	995
EIF3E	EIF3F	O00303	991
EIF3E	EIF3B	P55884	991
EIF3E	EIF3H	O15372	978
EIF3E	EIF4G1	Q04637	968
EIF3E	EIF3M	Q7L2H7	951
EIF3E	EIF3L	Q9Y262	935
EIF3E	PSMD12	O00232	920
EIF3E	EIF3K	Q9UBQ5	912
EIF3E	EIF3J	O75822	910
EIF3E	EIF3G	O75821	877
EIF3E	EIF3I	Q13347	867
EIF3E	EIF3A	Q14152	864
EIF3E	EIF5	P55010	811

IntAct

335 interactions, top by confidence:

A	B	Type	Score
EIF3M	EIF3F	psi-mi:“MI:0914”(association)	0.960
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3A	EIF3F	psi-mi:“MI:0914”(association)	0.910
EIF3H	EIF3F	psi-mi:“MI:0914”(association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
EIF3E	EIF3K	psi-mi:“MI:0915”(physical association)	0.880
EIF3L	EIF3E	psi-mi:“MI:0914”(association)	0.860
EIF3E	EIF3L	psi-mi:“MI:0407”(direct interaction)	0.860
EIF3D	EIF3E	psi-mi:“MI:0915”(physical association)	0.850
EIF3D	EIF3E	psi-mi:“MI:0407”(direct interaction)	0.850
EIF3C	EIF3E	psi-mi:“MI:0915”(physical association)	0.810
EIF3E	EIF3C	psi-mi:“MI:0915”(physical association)	0.810
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
EIF3C	EIF3F	psi-mi:“MI:0915”(physical association)	0.800

BioGRID (496): EIF3E (Two-hybrid), EIF3E (Two-hybrid), EIF3E (Affinity Capture-MS), RUNDC3A (Two-hybrid), C4orf19 (Two-hybrid), EIF3E (Two-hybrid), EIF3E (Affinity Capture-Western), EIF3E (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3E (Two-hybrid), GPBP1L1 (Two-hybrid)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: A1CKN7, A1D6T6, A4R796, A5AAA4, A6SM77, A7F3L0, A7RWP6, A8NY27, A8XFH3, A9UQS1, B0WAM5, B0XXL3, B3M4D9, B3NDH5, B4H5N1, B4HK67, B4IXG1, B4KY00, B4LG58, B4MYA1, B4N3B0, B4PK98, B4QMY7, B5DGH9, O61820, O77410, O94513, P0CN50, P0CN51, P60228, P60229, Q05AY2, Q0CNR3, Q0U0X1, Q1E170, Q1HQY6, Q1LUA8, Q29EX2, Q2F5R8, Q2HBQ2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
EIF3E	“up-regulates quantity by stabilization”	MCM7	binding
EIF3E	“up-regulates quantity”	PLAU	“translation regulation”
EIF3E	“up-regulates quantity”	BCL2L1	“translation regulation”
EIF3E	“down-regulates quantity”	MAD2L1	“translation regulation”
EIF3E	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Translation initiation complex formation	17	43.7×	8e-22
Ribosomal scanning and start codon recognition	17	43.7×	8e-22
Formation of the ternary complex, and subsequently, the 43S complex	15	43.7×	3e-19
L13a-mediated translational silencing of Ceruloplasmin expression	18	24.6×	1e-18
GTP hydrolysis and joining of the 60S ribosomal subunit	18	24.4×	1e-18
Formation of a pool of free 40S subunits	15	22.7×	8e-15

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	13	149.0×	4e-25
translational initiation	16	58.5×	3e-22
positive regulation of fibroblast proliferation	5	15.1×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — CESC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1793 predictions. Top by Δscore:

Variant	Effect	Δscore
8:108202980:TAC:T	donor_loss	1.0000
8:108202981:A:AC	donor_gain	1.0000
8:108202981:A:T	donor_loss	1.0000
8:108202982:C:CC	donor_gain	1.0000
8:108202982:CCT:C	donor_gain	1.0000
8:108203113:TGACC:T	acceptor_gain	1.0000
8:108203115:ACCC:A	acceptor_loss	1.0000
8:108203116:CC:C	acceptor_gain	1.0000
8:108203117:CC:C	acceptor_gain	1.0000
8:108203117:CCTA:C	acceptor_loss	1.0000
8:108203118:C:CC	acceptor_gain	1.0000
8:108203118:C:T	acceptor_gain	1.0000
8:108203118:CTA:C	acceptor_loss	1.0000
8:108203119:T:A	acceptor_loss	1.0000
8:108203399:A:AC	donor_gain	1.0000
8:108203400:C:CA	donor_gain	1.0000
8:108203400:CT:C	donor_gain	1.0000
8:108203400:CTA:C	donor_gain	1.0000
8:108203400:CTAA:C	donor_gain	1.0000
8:108203400:CTAAT:C	donor_gain	1.0000
8:108203499:ACATG:A	acceptor_gain	1.0000
8:108203500:CATG:C	acceptor_gain	1.0000
8:108203500:CATGC:C	acceptor_gain	1.0000
8:108203501:ATG:A	acceptor_gain	1.0000
8:108203502:TG:T	acceptor_gain	1.0000
8:108203504:C:CA	acceptor_loss	1.0000
8:108203504:C:CC	acceptor_gain	1.0000
8:108203505:T:C	acceptor_loss	1.0000
8:108203507:A:AC	acceptor_gain	1.0000
8:108203507:A:C	acceptor_gain	1.0000

AlphaMissense

2983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:108203110:A:T	V391E	1.000
8:108203414:A:C	I384S	1.000
8:108203414:A:T	I384N	1.000
8:108203420:G:T	A382D	1.000
8:108203421:C:G	A382P	1.000
8:108203426:A:G	L380P	1.000
8:108203433:C:G	A378P	1.000
8:108203441:A:C	I375S	1.000
8:108203441:A:T	I375N	1.000
8:108203444:A:C	L374W	1.000
8:108203453:A:T	I371N	1.000
8:108203455:C:A	W370C	1.000
8:108203455:C:G	W370C	1.000
8:108203457:A:G	W370R	1.000
8:108203457:A:T	W370R	1.000
8:108203461:T:A	E368D	1.000
8:108203461:T:G	E368D	1.000
8:108203462:T:A	E368V	1.000
8:108203465:G:T	A367D	1.000
8:108203466:C:G	A367P	1.000
8:108203486:A:C	L360W	1.000
8:108203486:A:G	L360S	1.000
8:108203496:C:G	A357P	1.000
8:108203498:A:C	L356W	1.000
8:108203498:A:G	L356S	1.000
8:108214616:A:T	I351N	1.000
8:108214626:G:C	H348D	1.000
8:108214628:A:C	I347S	1.000
8:108214628:A:T	I347N	1.000
8:108214631:C:G	R346P	1.000

dbSNP variants (sampled 300 via entrez): RS1000032305 (8:108236944 C>G), RS1000052394 (8:108211696 C>A,T), RS1000067524 (8:108218485 A>C), RS1000148732 (8:108243582 T>C), RS1000208816 (8:108246295 G>A,C,T), RS1000210420 (8:108211770 C>T), RS1000245024 (8:108224348 A>C), RS1000248592 (8:108223893 T>C), RS1000272843 (8:108218185 T>A,C), RS1000319071 (8:108240809 G>A), RS1000382982 (8:108241035 A>G), RS1000409900 (8:108246855 A>C), RS1000427448 (8:108205627 T>C,G), RS1000497069 (8:108241383 C>A,G), RS1000539183 (8:108240937 A>G)

Disease associations

OMIM: gene MIM:602210 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001144_5	Dupuytren’s disease	8.000000e-15
GCST002545_2	Ossification of the posterior longitudinal ligament of the spine	2.000000e-13
GCST004858_11	Dupuytren’s disease	1.000000e-32
GCST006661_112	Male-pattern baldness	5.000000e-17
GCST006661_172	Male-pattern baldness	2.000000e-11
GCST006661_282	Male-pattern baldness	5.000000e-27
GCST006976_78	Macular thickness	2.000000e-09
GCST006979_473	Heel bone mineral density	2.000000e-12
GCST008526_12	Coffee consumption	8.000000e-07
GCST010703_334	Brain morphology (MOSTest)	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0009270	heel bone mineral density
EFO:0006781	coffee consumption measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725122 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	Kd	512.2	nM	CHEMBL5653589
6.29	ED50	512.2	nM	CHEMBL5653589
6.01	IC50	970	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148147: Binding affinity to human EIF3E incubated for 45 mins by Kinobead based pull down assay	kd	0.5122	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178469: Inhibition of EIF3E (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.9700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, affects cotreatment, increases abundance (+1 more)	4
bisphenol A	increases expression, affects expression, decreases expression	3
Valproic Acid	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects localization, increases expression, affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651189	Binding	Binding affinity to human EIF3E incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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