EIF4B

Summary

EIF4B (eukaryotic translation initiation factor 4B, HGNC:3285) is a protein-coding gene on chromosome 12q13.13, encoding Eukaryotic translation initiation factor 4B (P23588). Required for the binding of mRNA to ribosomes. It is a selective cancer dependency (DepMap: 66.6% of cell lines).

Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder.

Source: NCBI Gene 1975 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 66.6% of screened cell lines
• MANE Select transcript: NM_001417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3285
Approved symbol	EIF4B
Name	eukaryotic translation initiation factor 4B
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000063046
Ensembl biotype	protein_coding
OMIM	603928
Entrez	1975

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 19 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000262056, ENST00000416762, ENST00000420463, ENST00000549077, ENST00000549481, ENST00000549592, ENST00000549645, ENST00000550025, ENST00000550390, ENST00000550704, ENST00000551002, ENST00000551527, ENST00000552490, ENST00000553209, ENST00000859795, ENST00000859796, ENST00000859797, ENST00000859798, ENST00000961686, ENST00000961687, ENST00000961688, ENST00000961689, ENST00000961690, ENST00000961691, ENST00000961692, ENST00000961693, ENST00000961694

RefSeq mRNA: 3 — MANE Select: NM_001417 NM_001300821, NM_001330654, NM_001417

CCDS: CCDS41788, CCDS73474, CCDS86303

Canonical transcript exons

ENST00000262056 — 15 exons

Exon	Start	End
ENSE00000746225	53021806	53021860
ENSE00000746239	53037409	53037622
ENSE00000746241	53038356	53038411
ENSE00000838126	53039238	53039343
ENSE00001309333	53040143	53042215
ENSE00002278277	53006456	53006496
ENSE00003496850	53034612	53034709
ENSE00003513291	53018798	53019006
ENSE00003527494	53022493	53022627
ENSE00003574289	53027782	53027919
ENSE00003627897	53016473	53016610
ENSE00003653367	53028015	53028188
ENSE00003682015	53033806	53034034
ENSE00003684301	53039630	53039702
ENSE00003686995	53019910	53020026

Expression profiles

Bgee: expression breadth ubiquitous, 308 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1255 / max 209.8827, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125681	15.8895	1795
125679	1.5954	963
125685	0.3955	174
125680	0.2451	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.63	gold quality
cortical plate	UBERON:0005343	99.45	gold quality
ganglionic eminence	UBERON:0004023	99.29	gold quality
left ovary	UBERON:0002119	99.28	gold quality
colonic epithelium	UBERON:0000397	99.27	gold quality
ovary	UBERON:0000992	99.23	gold quality
islet of Langerhans	UBERON:0000006	99.21	gold quality
stromal cell of endometrium	CL:0002255	99.18	gold quality
body of pancreas	UBERON:0001150	99.15	gold quality
right ovary	UBERON:0002118	99.12	gold quality
tendon	UBERON:0000043	99.09	gold quality
ventricular zone	UBERON:0003053	99.09	gold quality
adrenal tissue	UBERON:0018303	99.08	gold quality
monocyte	CL:0000576	99.02	gold quality
mononuclear cell	CL:0000842	99.02	gold quality
leukocyte	CL:0000738	99.01	gold quality
endocervix	UBERON:0000458	98.99	gold quality
mucosa of stomach	UBERON:0001199	98.97	gold quality
endometrium epithelium	UBERON:0004811	98.97	gold quality
muscle of leg	UBERON:0001383	98.96	gold quality
gastrocnemius	UBERON:0001388	98.93	gold quality
gall bladder	UBERON:0002110	98.92	gold quality
lymph node	UBERON:0000029	98.83	gold quality
ectocervix	UBERON:0012249	98.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.78	gold quality
body of uterus	UBERON:0009853	98.78	gold quality
embryo	UBERON:0000922	98.77	gold quality
muscle organ	UBERON:0001630	98.77	gold quality
skeletal muscle organ	UBERON:0014892	98.77	gold quality
smooth muscle tissue	UBERON:0001135	98.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	397.76
E-HCAD-31	no	18.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

146 targeting EIF4B, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 66.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 30)

• The solution structure of the eIF4B RNA recognition motif (RRM) domain is reported; the core RRM domain provides only a relative weak interaction with RNA targets and appears to require extensions at the N- and C-terminus for high-affinity binding. (PMID:12885229)
• eIF4B may mediate some of the effects of the ribosomal protein S6 kinases on translation (PMID:15071500)
• data indicate that eIF4B and 4H stimulate the nuclease activity of herpes simplex virus vhs, and they provide evidence that additional mammalian factors are required for targeting to the encephalomyocarditis virus IRES (PMID:15078951)
• Phosphorylation of eIF4B on Ser422 by p90 ribosomal protein S6 kinase (RSK) and S6K is physiologically significant, as it increases the interaction of eIF4B with the eukaryotic translation initiation factor 3. (PMID:16763566)
• The interaction of eIF4AI with two accessory factors, eIF4B and eIF4H, was studied. (PMID:18719248)
• Data show that reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. (PMID:19369421)
• Studies indicate that eIF4A (DDX2), together with its accessory proteins eIF4B and eIF4H, is thought to act as a helicase that unwinds secondary structures in the mRNA 5’ UTR. (PMID:21427765)
• Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B. (PMID:21840318)
• ORF45/RSK axis-induced eIF4B phosphorylation is involved in translational regulation and is required for optimal KSHV lytic replication. (PMID:21994950)
• our results identify eIF4B as a critical substrate of Pim kinases in mediating the activity of Abl oncogenes (PMID:23749639)
• Overexpression of pim-2 may inhibit the apoptosis of prostate cancer cells through phosphorylation of eIF4B, thus promoting tumorigenesis. (PMID:23813671)
• Report EIF4B binding within the IRES domain V of the coxsackie virus B3 mutant strain. (PMID:24063684)
• eIF4B-driven expression of these key survival proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in DLBCL (PMID:24135829)
• eIF4B is the RSK downstream effector responsible for elevated Lamgamma2 as well as MYC protein in neoplastic epithelial cells. (PMID:24205356)
• The protein level of eukaryotic translation initiation factor 4B (eIF4B) was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with influenza A virus. (PMID:24829357)
• EIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy. (PMID:25129346)
• MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eIF4B. (PMID:25955794)
• Results indicate that eIF4B integrates the signals from Pim and PI3K/Akt/mTOR pathways in Abl-expressing leukemic cells. (PMID:26848623)
• Synthesis of MCL1, an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B signaling. (PMID:27528663)
• Together, our data show that mAChRs modulate eIF4B phosphorylation via the ERK1/2 and PKC signaling pathways in SNU-407 colon cancer cells. (PMID:27773818)
• High EIF4B expression is associated with Malignant Grade in Prostate Cancer. (PMID:29124675)
• FASN-induced S6 kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in diffuse large B-cell lymphoma. (PMID:29483509)
• eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated amyotrophic lateral sclerosis. (PMID:31023341)
• Long noncoding RNA GMAN promotes hepatocellular carcinoma progression by interacting with eIF4B. (PMID:31875526)
• eIF4B enhances ATF4 expression and contributes to cellular adaptation to asparagine limitation in BRAF-mutated A375 melanoma. (PMID:34403810)
• CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4beta. (PMID:35593475)
• Backbone resonance assignments of the C-terminal region of human translation initiation factor eIF4B. (PMID:37368134)
• DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis. (PMID:37895289)
• Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study. (PMID:39215053)
• Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs. (PMID:39225047)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4bb	ENSDARG00000010194
danio_rerio	eif4ba	ENSDARG00000017439
drosophila_melanogaster	eIF4B	FBGN0020660

Paralogs (1): EIF4H (ENSG00000106682)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4B — P23588 (reviewed: P23588)

All UniProt accessions (8): P23588, E7EX17, F8VP89, F8VRU1, F8VSC7, F8VX11, F8VYE9, F8W0K0

UniProt curated annotations — full annotation on UniProt →

Function. Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5’-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F.

Subunit / interactions. Self-associates and interacts with EIF3 p170 subunit.

Post-translational modifications. Phosphorylated at Ser-422 by RPS6KA1 and RPS6KB1; phosphorylation enhances the affinity of EIF4B for the EIF3 complex. In response to mTORC1 activation, RPS6KA1-mediated phosphorylation at ‘Ser-406’ and ‘Ser-422’ stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function.

Isoforms (2)

UniProt ID	Names	Canonical?
P23588-1	1	yes
P23588-2	2

RefSeq proteins (3): NP_001287750, NP_001317583, NP_001408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR033107	EIF-4B_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (64 total): modified residue 23, compositionally biased region 14, sequence conflict 7, strand 5, region of interest 3, helix 3, mutagenesis site 2, turn 2, chain 1, domain 1, cross-link 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6FEC	ELECTRON MICROSCOPY	6.3
1WI8	SOLUTION NMR
2J76	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23588-F1	51.91	0.00

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 (24): 93, 192, 207, 219, 283, 359, 365, 406, 409, 412, 418, 422, 425, 445, 459, 462, 497, 498, 500, 504 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
406	non-phosphorylatable mutant whose expression results in reduced slc4a7 protein levels in tsc2-deficient cells accompanie
422	non-phosphorylatable mutant whose expression results in reduced slc4a7 protein levels in tsc2-deficient cells accompanie

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-166208	mTORC1-mediated signalling
R-HSA-429947	Deadenylation of mRNA
R-HSA-72649	Translation initiation complex formation
R-HSA-72662	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors
R-HSA-9820865	Z-decay: degradation of maternal mRNAs by zygotically expressed factors

MSigDB gene sets: 299 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MODULE_151, GCM_NPM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_TRANSLATIONAL_INITIATION, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, USF_C, GOBP_TRANSLATION, PID_MTOR_4PATHWAY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (5): formation of translation preinitiation complex (GO:0001731), regulation of translational initiation (GO:0006446), eukaryotic translation initiation factor 4F complex assembly (GO:0097010), translation (GO:0006412), translational initiation (GO:0006413)

GO Molecular Function (7): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), RNA strand annealing activity (GO:0033592), RNA strand-exchange activity (GO:0034057), ribosomal small subunit binding (GO:0043024), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), eukaryotic translation initiation factor 4F complex (GO:0016281)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cap-dependent Translation Initiation	3
Maternal to zygotic transition (MZT)	2
Eukaryotic Translation Initiation	1
MTOR signalling	1
Deadenylation-dependent mRNA decay	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	3
single-stranded RNA binding	2
binding	2
cytoplasm	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
regulation of translation	1
protein-containing complex assembly	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
nucleic acid binding	1
translation factor activity	1
catalytic activity, acting on RNA	1
annealing activity	1
double-stranded RNA binding	1
ribosome binding	1
cellular anatomical structure	1
RNA cap binding complex	1

Protein interactions and networks

STRING

3351 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4B	EIF4A1	P04765	999
EIF4B	EIF4A2	Q14240	999
EIF4B	EIF4E	P06730	999
EIF4B	EIF4G1	Q04637	998
EIF4B	EIF1	P41567	994
EIF4B	PABPC1	P11940	993
EIF4B	EIF5	P55010	984
EIF4B	RPS6KB1	P23443	915
EIF4B	EIF4H	Q15056	915
EIF4B	RPS6	P08227	894
EIF4B	EFNA1	P20827	887
EIF4B	DHX29	Q7Z478	849
EIF4B	RPTOR	Q8N122	831
EIF4B	EIF3B	P55884	827
EIF4B	EIF5B	O60841	824

IntAct

174 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EIF4B	EIF3A	psi-mi:“MI:0915”(physical association)	0.670
EIF3A	EIF4B	psi-mi:“MI:0407”(direct interaction)	0.670
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
CRYAA	EIF4B	psi-mi:“MI:0915”(physical association)	0.560
EIF4B	ATN1	psi-mi:“MI:0915”(physical association)	0.560
EIF4B	KLK6	psi-mi:“MI:0915”(physical association)	0.560
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
TINF2	EIF4B	psi-mi:“MI:0915”(physical association)	0.510
EIF4B		psi-mi:“MI:0915”(physical association)	0.500
PLK1	EIF4B	psi-mi:“MI:0217”(phosphorylation reaction)	0.490
EIF4B	PLK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.490
PLK1	EIF4B	psi-mi:“MI:0403”(colocalization)	0.490
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (526): EIF4B (Reconstituted Complex), EIF4B (Affinity Capture-MS), EIF4B (Affinity Capture-MS), CCT6A (Co-fractionation), CFL1 (Co-fractionation), CSTF2 (Co-fractionation), CTPS1 (Co-fractionation), DDX39A (Co-fractionation), DOHH (Co-fractionation), EIF4B (Co-fractionation), EIF4G1 (Co-fractionation), GSPT1 (Co-fractionation), HSPB1 (Co-fractionation), IMPDH2 (Co-fractionation), KHSRP (Co-fractionation)

ESM2 similar proteins: B2GV05, B5FXN8, G3V9R8, O08583, O75525, O77768, P07910, P19600, P23588, P52756, P55795, P70333, P97379, P97855, Q08DJ0, Q0VFL7, Q13148, Q13283, Q1RMU5, Q28FB9, Q32LC7, Q3SZF3, Q3T0I4, Q58EA2, Q5R5W2, Q5R9L3, Q5RA82, Q5RB87, Q5RD26, Q5SRX1, Q5VWX1, Q5ZLN5, Q60HC3, Q64012, Q6AY09, Q6GLW1, Q86SE5, Q86V81, Q8BGD9, Q8BTF8

Diamond homologs: J9VI89, O14369, P23588, P27476, P41891, Q03250, Q05966, Q15056, Q1JPH6, Q5RBR8, Q5XI72, Q6Z1C0, Q8BGD9, Q9WUK2, A0A2R8Y4L2, A4FV72, A5A6H4, A7VJC2, G5EFS2, O13741, O13759, O13845, O22173, O43347, O88569, P04256, P09651, P09867, P17130, P19682, P19683, P19684, P22626, P28644, P32831, P33240, P39697, P42696, P49312, P49313

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
RPS6KA1	up-regulates	EIF4B	phosphorylation
RPS6KB1	up-regulates	EIF4B	phosphorylation
AKT	up-regulates	EIF4B	phosphorylation
AKT1	up-regulates	EIF4B	phosphorylation
RPS6K	up-regulates	EIF4B	phosphorylation
EIF3_complex	“up-regulates activity”	EIF4B	stabilization
EIF4B	“form complex”	48S_initiation_complex	binding
CDK13	“up-regulates activity”	EIF4B	phosphorylation
CyclinK/CDK13	“up-regulates activity”	EIF4B	phosphorylation
EIF4B	“up-regulates activity”	EIF4A1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 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
Activation of BAD and translocation to mitochondria	6	35.1×	2e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	31.0×	2e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	31.0×	2e-06
Activation of BH3-only proteins	6	22.9×	9e-06
Intrinsic Pathway for Apoptosis	8	18.0×	2e-06
RHO GTPases activate PKNs	6	14.6×	9e-05
Signaling by TGFBR3	5	14.2×	5e-04
SARS-CoV-1-host interactions	10	13.5×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	6	42.7×	2e-06
negative regulation of telomere maintenance via telomerase	5	23.2×	6e-04
translational initiation	9	20.4×	6e-07
positive regulation of translation	9	13.0×	1e-05
protein targeting	5	11.6×	6e-03
intracellular protein localization	9	6.0×	3e-03
mRNA splicing, via spliceosome	9	5.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2622 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53016466:A:AG	acceptor_gain	1.0000
12:53016467:A:AG	acceptor_gain	1.0000
12:53016468:A:G	acceptor_gain	1.0000
12:53016469:A:AG	acceptor_gain	1.0000
12:53016469:ACAGC:A	acceptor_loss	1.0000
12:53016470:C:G	acceptor_gain	1.0000
12:53016471:A:AG	acceptor_gain	1.0000
12:53016472:G:GT	acceptor_gain	1.0000
12:53016472:GC:G	acceptor_gain	1.0000
12:53016472:GCA:G	acceptor_gain	1.0000
12:53016472:GCAA:G	acceptor_gain	1.0000
12:53016472:GCAAA:G	acceptor_gain	1.0000
12:53016601:G:GT	donor_gain	1.0000
12:53016605:G:GT	donor_gain	1.0000
12:53016607:GATG:G	donor_gain	1.0000
12:53018791:A:AG	acceptor_gain	1.0000
12:53018794:CTA:C	acceptor_loss	1.0000
12:53018796:A:AG	acceptor_gain	1.0000
12:53018796:A:C	acceptor_loss	1.0000
12:53018797:G:GT	acceptor_gain	1.0000
12:53018797:GT:G	acceptor_gain	1.0000
12:53018797:GTT:G	acceptor_gain	1.0000
12:53018797:GTTT:G	acceptor_gain	1.0000
12:53018797:GTTTC:G	acceptor_gain	1.0000
12:53018986:G:GT	donor_gain	1.0000
12:53018999:GAT:G	donor_gain	1.0000
12:53019002:TAAAT:T	donor_gain	1.0000
12:53019003:AAAT:A	donor_gain	1.0000
12:53019004:AAT:A	donor_gain	1.0000
12:53019005:AT:A	donor_gain	1.0000

AlphaMissense

3990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53016509:T:A	L17Q	1.000
12:53016509:T:C	L17P	1.000
12:53016517:T:C	F20L	1.000
12:53016518:T:C	F20S	1.000
12:53016518:T:G	F20C	1.000
12:53016519:T:A	F20L	1.000
12:53016519:T:G	F20L	1.000
12:53016577:T:A	W40R	1.000
12:53016577:T:C	W40R	1.000
12:53016578:G:C	W40S	1.000
12:53016579:G:C	W40C	1.000
12:53016579:G:T	W40C	1.000
12:53018864:T:A	L73H	1.000
12:53018864:T:C	L73P	1.000
12:53018866:C:A	P74T	1.000
12:53018866:C:T	P74S	1.000
12:53018867:C:A	P74H	1.000
12:53018873:C:A	A76D	1.000
12:53018876:C:A	P77Q	1.000
12:53018882:C:A	A79D	1.000
12:53018885:C:A	A80D	1.000
12:53018917:C:A	P91T	1.000
12:53018917:C:T	P91S	1.000
12:53018918:C:A	P91H	1.000
12:53018918:C:G	P91R	1.000
12:53018929:C:A	P95T	1.000
12:53018929:C:T	P95S	1.000
12:53018930:C:A	P95H	1.000
12:53018930:C:G	P95R	1.000
12:53018930:C:T	P95L	1.000

dbSNP variants (sampled 300 via entrez): RS1000161747 (12:53029513 C>CTA), RS1000168433 (12:53037264 A>G,T), RS1000172573 (12:53005101 C>T), RS1000665301 (12:53032189 A>G), RS1000773746 (12:53038679 G>C), RS1000781558 (12:53038715 GCTGAGGCA>G), RS1000837163 (12:53015206 A>G), RS1000852346 (12:53039957 T>A,C,G), RS1000957565 (12:53009427 A>C,G), RS1001081372 (12:53038402 G>A,C), RS1001110746 (12:53009072 C>T), RS1001306957 (12:53032909 G>A), RS1001369754 (12:53014902 C>T), RS1001395345 (12:53031053 C>T), RS1001413270 (12:53033522 T>G)

Disease associations

OMIM: gene MIM:603928 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001147_14	Prostate cancer	5.000000e-09
GCST010796_3114	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3308928 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Kd	0.1	nM	CHEMBL5653589
10.00	ED50	0.1	nM	CHEMBL5653589
6.35	Kd	449	nM	CHEMBL3752910
6.35	ED50	449	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 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	2148306: Binding affinity to human EIF4B incubated for 45 mins by Kinobead based pull down assay	kd	0.0001	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148306: Binding affinity to human EIF4B incubated for 45 mins by Kinobead based pull down assay	kd	0.4490	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects localization, decreases expression, increases activity, increases expression	3
Aflatoxin B1	increases methylation, increases phosphorylation	3
azoxystrobin	increases expression, increases phosphorylation	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, decreases phosphorylation	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Acetaminophen	decreases expression	2
Cisplatin	increases phosphorylation, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
fluxapyroxad	increases phosphorylation	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
moringin	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
chlortoluron	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
tributyltin	affects expression, increases phosphorylation	1
beta-lapachone	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases phosphorylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, increases expression	1
evodiamine	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226424	Binding	Inhibition of eIF4B interaction with mRNA cap structure in presence of 0.6 mM m7GDP at 50 uM by chemical cross-linking assay	Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. — Nat Chem Biol

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8KR	Ubigene HCT 116 EIF4B KO	Cancer cell line	Male
CVCL_E0CJ	Ubigene HeLa EIF4B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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