EIF4A1

Summary

EIF4A1 (eukaryotic translation initiation factor 4A1, HGNC:3282) is a protein-coding gene on chromosome 17p13.1, encoding Eukaryotic initiation factor 4A-I (P60842). ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

Enables double-stranded RNA binding activity and translation initiation factor activity. Involved in cytoplasmic translational initiation and positive regulation of transcription by RNA polymerase II. Located in nuclear stress granule; perinuclear region of cytoplasm; and plasma membrane.

Source: NCBI Gene 1973 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 17 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_001416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3282
Approved symbol	EIF4A1
Name	eukaryotic translation initiation factor 4A1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	DDX2A, EIF-4A
Ensembl gene	ENSG00000161960
Ensembl biotype	protein_coding
OMIM	602641
Entrez	1973

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 23 protein_coding, 18 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000293831, ENST00000396527, ENST00000577269, ENST00000577731, ENST00000577738, ENST00000577929, ENST00000578324, ENST00000578476, ENST00000578495, ENST00000578569, ENST00000578754, ENST00000579085, ENST00000579139, ENST00000580461, ENST00000580886, ENST00000581384, ENST00000581544, ENST00000581770, ENST00000581808, ENST00000581841, ENST00000582050, ENST00000582169, ENST00000582213, ENST00000582746, ENST00000582848, ENST00000583217, ENST00000583389, ENST00000583802, ENST00000583899, ENST00000584054, ENST00000584712, ENST00000584784, ENST00000584798, ENST00000584860, ENST00000584901, ENST00000585024, ENST00000879166, ENST00000879167, ENST00000879168, ENST00000879169, ENST00000934298, ENST00000934299, ENST00000934300, ENST00000934301, ENST00000934302, ENST00000934303, ENST00000934304

RefSeq mRNA: 2 — MANE Select: NM_001416 NM_001204510, NM_001416

CCDS: CCDS11113, CCDS58511

Canonical transcript exons

ENST00000293831 — 11 exons

Exon	Start	End
ENSE00001485271	7578342	7579006
ENSE00003461960	7577827	7577916
ENSE00003516120	7578165	7578244
ENSE00003527449	7574546	7574678
ENSE00003531784	7576524	7576692
ENSE00003586333	7577056	7577165
ENSE00003601249	7577344	7577487
ENSE00003650221	7574260	7574308
ENSE00003668494	7575119	7575258
ENSE00003790537	7577569	7577706
ENSE00003848811	7572825	7572864

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.5288 / max 1551.1857, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159262	118.2722	1824
159263	0.1836	62
159264	0.0730	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	99.77	gold quality
embryo	UBERON:0000922	99.61	gold quality
ganglionic eminence	UBERON:0004023	99.61	gold quality
cortical plate	UBERON:0005343	99.60	gold quality
left uterine tube	UBERON:0001303	99.57	gold quality
granulocyte	CL:0000094	99.56	gold quality
stromal cell of endometrium	CL:0002255	99.56	gold quality
islet of Langerhans	UBERON:0000006	99.55	gold quality
skin of abdomen	UBERON:0001416	99.53	gold quality
upper lobe of left lung	UBERON:0008952	99.53	gold quality
omental fat pad	UBERON:0010414	99.53	gold quality
esophagus mucosa	UBERON:0002469	99.51	gold quality
zone of skin	UBERON:0000014	99.50	gold quality
bone element	UBERON:0001474	99.50	gold quality
right ovary	UBERON:0002118	99.50	gold quality
bone marrow	UBERON:0002371	99.50	gold quality
ovary	UBERON:0000992	99.48	gold quality
adipose tissue	UBERON:0001013	99.48	gold quality
left ovary	UBERON:0002119	99.48	gold quality
ventricular zone	UBERON:0003053	99.48	gold quality
lower esophagus mucosa	UBERON:0035834	99.48	gold quality
bone marrow cell	CL:0002092	99.47	gold quality
uterine cervix	UBERON:0000002	99.47	gold quality
vermiform appendix	UBERON:0001154	99.47	gold quality
skin of leg	UBERON:0001511	99.47	gold quality
lung	UBERON:0002048	99.47	gold quality
tonsil	UBERON:0002372	99.47	gold quality
smooth muscle tissue	UBERON:0001135	99.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.46	gold quality
fallopian tube	UBERON:0003889	99.46	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	135.10
E-HCAD-4	yes	71.13
E-CURD-46	yes	29.77
E-MTAB-9221	yes	27.50
E-CURD-88	yes	20.35
E-ANND-3	yes	14.98
E-CURD-122	yes	12.62
E-MTAB-5061	yes	11.66
E-CURD-112	yes	11.20
E-MTAB-9067	yes	10.51
E-CURD-126	no	2333.91
E-MTAB-6911	no	1981.29
E-MTAB-9689	no	1241.75
E-MTAB-8271	no	1002.95
E-HCAD-5	no	20.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, ZBED1

miRNA regulators (miRDB)

63 targeting EIF4A1, 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-6833-3P	100.00	70.63	3197
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4505	99.27	67.81	2678

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Comparative characterization of two DEAD-box RNA helicases in superfamily II: human translation-initiation factor 4A and hepatitis C virus non-structural protein 3 (NS3) helicase. (PMID:11903057)
• Results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA-3 domain of eIF4Gc contributes to the mechanism by which Pdcd4 inhibits translation. (PMID:15082783)
• analysis of cells of eIF4GIf molecules lacking either the PABP-binding site, the eIF3-binding site, the middle domain eIF4A-binding site, or the C-terminal segment that includes the second eIF4A-binding site (PMID:17130132)
• Results report that 15d-PGJ2 blocks translation through inactivation of translational initiation factor eIF4A. (PMID:18034160)
• the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. (PMID:18296639)
• The interaction of eIF4AI with two accessory factors, eIF4B and eIF4H, was studied. (PMID:18719248)
• Study reports the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. (PMID:19203580)
• These findings identify PKP1 as a regulator of translation and proliferation via modulation of eIF4A1 activity. (PMID:20156963)
• Inhibition of eIF4A reduced the synthesis of APP and tau. (PMID:20927385)
• EIF4A and eIF4G proteins are not responsible for the selective translation of viral mRNAs and the translational shut-off of cellular protein synthesis. (PMID:21377182)
• 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)
• analysis of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G (PMID:21454508)
• Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B. (PMID:21840318)
• study found Burkholderia pseudomallei BPSL1549 acted as a potent cytotoxin against eukaryotic cells; it promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation (PMID:22076380)
• The results indicated that eIF4AI and eIF4AII expression are linked and that the two protein isoforms exhibit functional differences. (PMID:22589333)
• Regulation of MUC1-C expression is mediated by the PI3K/AKT pathway and the eIF4A RNA helicase. (PMID:22689062)
• Eukaryotic translation initiation factor 4A1 (eIF4A1) is a direct target of miR-US25-2-3p. (PMID:23747307)
• Findings implicate phosphorylation of eIF4G1(Ser1232) by Cdk1:cyclin B and its inhibitory effects on eIF4A helicase activity in the mitotic translation initiation shift. (PMID:24248602)
• The E186 residue was found to be of significance for RNA-dependent ATPase activity for eIF4AI alone and in the presence of eIF4AI-binding domains of eIF4GI, binding between eIF4AI and eIF4GI domains were also significantly influenced by mutation of E186. (PMID:24471916)
• Increased Expression of EIF4A1 is associated with poor response to Brachytherapy in Cervical Cancer. (PMID:24844222)
• Studies indicate that eukaryotic initiation factor 4AI (EIF4AI) undergoes large conformational transitions, while unwinding RNA hairpins. (PMID:24909782)
• report of an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds (PMID:25079319)
• Data indicate that caspase recruitment domain family, member 11 protein CARD11 has complex 5’UTRs and is sensitive to eIF4A RNA helicase inhibition. (PMID:25320244)
• Immunohistochemical analysis was performed on over 3000 breast tumors to investigate the relationship among expression of eIF4A1, the helicase-modulating proteins eIF4B, eIF4E and PDCD4, and clinical outcome. (PMID:25611378)
• demonstrate that DAP5 associates with eIF2beta and eIF4AI to stimulate IRES-dependent translation of cellular mRNAs (PMID:25779044)
• Collectively, these data suggested that a potential role of NS4A in antagonizing host antiviral defense is by recruiting eIF4AI and escaping the translation inhibition mediated by PKR. (PMID:25866185)
• eIF4A functions as an adenosine triphosphate-dependent processive helicase when complexed with two accessory proteins, eIF4G and eIF4B. (PMID:26113725)
• Studies indicate a developing focus on targeting eukaryotic initiation factor 4A eIF4A1 and eIF4A2 as cancer therapy. (PMID:26614665)
• miR-1284 can function as a new regulator to reduce gastric cancer multidrug resistant cells by targeting EIF4A1. (PMID:26936591)
• our data identify the eIF4F complex as an important upstream regulator of TORC1, which acts via TSC2 to inactivate TORC1 upon withdrawal of amino acids (PMID:26988032)
• our data demonstrate that the common effects of eIF4A1 and eIF4E on translation are mediated by the coding region and 3’UTR (PMID:27879264)
• Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer (PMID:28466778)
• Star-PAP-specific polyadenylation sites usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN and the long non-coding RNA NEAT1. (PMID:28911096)
• Results indicate that ubiquitin specific peptidase 9, X-linked (USP9X) is a regulator of the translation initiation process via deubiquitination of eukaryotic translation initiation factor 4A1 (eIF4A1), which is a substrate of USP9X in vivo. (PMID:29228324)
• Elatol’s identification as an eIF4A1 inhibitor with in vivo antitumor activities provides proof of principle for target-based screening against this highly promising target for cancer therapy. (PMID:29844128)
• Results suggest that rev protein, HIV-1 (Rev) regulates the association of nuclear cap-binding protein NCBP 80 kDa subunit (CBP80) and eukaryotic translation initiation factor 4A1 (eIF4AI) with the unspliced mRNA in the cytoplasm and the nucleus, respectively, during HIV-1 replication. (PMID:30239828)
• RocA targets the “bi-molecular cavity” formed characteristically by eIF4A1 and a sharply bent pair of consecutive purines in the RNA to inhibit genetic translation. (PMID:30595437)
• Besides catalyzing serine synthesis, PHGDH promotes pancreatic cancer development through enhancing the translation initiations by interacting with eIF4A1 and eIF4E. (PMID:30744688)
• This work demonstrates the importance of eIF4A in translational control of pancreatic tumour metabolism. (PMID:31723131)
• remodels local 5’ untranslated region structures (PMID:31888698)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eif4a1	ENSMUSG00000059796
rattus_norvegicus	Eif4a1	ENSRNOG00000030628
drosophila_melanogaster	eIF4A	FBGN0001942
caenorhabditis_elegans		WBGENE00002083

Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), DDX17 (ENSG00000100201), DDX49 (ENSG00000105671), DDX50 (ENSG00000107625), DDX5 (ENSG00000108654), DDX25 (ENSG00000109832), DDX6 (ENSG00000110367), DDX55 (ENSG00000111364), DDX59 (ENSG00000118197), DDX54 (ENSG00000123064), DDX39A (ENSG00000123136), DDX27 (ENSG00000124228), DDX31 (ENSG00000125485), DDX56 (ENSG00000136271), EIF4A3 (ENSG00000141543), DDX46 (ENSG00000145833), DDX4 (ENSG00000152670), EIF4A2 (ENSG00000156976), DDX19B (ENSG00000157349), DDX21 (ENSG00000165732), DDX19A (ENSG00000168872), TDRD12 (ENSG00000173809), DDX23 (ENSG00000174243), DDX10 (ENSG00000178105), DDX28 (ENSG00000182810), DDX41 (ENSG00000183258), DDX53 (ENSG00000184735), DDX51 (ENSG00000185163), DDX42 (ENSG00000198231), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

Eukaryotic initiation factor 4A-I — P60842 (reviewed: P60842)

Alternative names: ATP-dependent RNA helicase eIF4A-1

All UniProt accessions (15): P60842, J3KRC2, J3KS25, J3KS93, J3KSZ0, J3KT12, J3KTN0, J3QKZ9, J3QL43, J3QL52, J3QLN6, J3QQP0, J3QR64, J3QRP5, J3QS69

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5’-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. As a result, promotes cell proliferation and growth.

Subunit / interactions. eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Interacts with PAIP1, EIF4E and UPF2. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. May interact with NOM1. Interacts with PDCD4; this interferes with the interaction between EIF4A and EIF4G. Interacts with RBM4. Interacts with DDX3X in an RNA-independent manner. Interacts with PKP1 (via N-terminus); the interaction promotes EIF4A1 recruitment to the cap-dependent translation complex and EIF4A1 ATPase activity. Interacts with CEP112. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.

Subcellular location. Cytoplasm. Perinuclear region. Cell membrane. Stress granule.

Activity regulation. Helicase activity and function in translation are inhibited by interaction with PDCD4.

Similarity. Belongs to the DEAD box helicase family. eIF4A subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P60842-1	1	yes
P60842-2	2
P60842-3	3

RefSeq proteins (2): NP_001191439, NP_001407* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR001650	Helicase_C-like	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014014	RNA_helicase_DEAD_Q_motif	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR044728	EIF4A_DEADc	Domain

Pfam: PF00270, PF00271

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (72 total): helix 25, strand 17, modified residue 8, cross-link 6, turn 4, splice variant 3, initiator methionine 2, domain 2, short sequence motif 2, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5ZBZ	X-RAY DIFFRACTION	1.31
9DTS	X-RAY DIFFRACTION	1.69
9I9G	X-RAY DIFFRACTION	1.7
9AVR	X-RAY DIFFRACTION	1.91
5ZC9	X-RAY DIFFRACTION	2
2G9N	X-RAY DIFFRACTION	2.25
7PPZ	X-RAY DIFFRACTION	2.52
9I9F	X-RAY DIFFRACTION	2.73
2ZU6	X-RAY DIFFRACTION	2.8
7PQ0	X-RAY DIFFRACTION	3
3EIQ	X-RAY DIFFRACTION	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
8XXN	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
8HUJ	ELECTRON MICROSCOPY	3.76
9BLN	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60842-F1	87.48	0.64

Functional residue map

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

Ligand- & substrate-binding residues (1): 76–83

Post-translational modifications (14): 118, 158, 174, 193, 238, 146, 225, 238, 309, 369, 381, 2, 2, 4

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
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
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 368 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, PAX4_01, E2F4DP1_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC1, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (4): cytoplasmic translational initiation (GO:0002183), translational initiation (GO:0006413), positive regulation of transcription by RNA polymerase II (GO:0045944), translation (GO:0006412)

GO Molecular Function (14): RNA cap binding (GO:0000339), RNA binding (GO:0003723), RNA helicase activity (GO:0003724), double-stranded RNA binding (GO:0003725), mRNA binding (GO:0003729), translation initiation factor activity (GO:0003743), helicase activity (GO:0004386), ATP binding (GO:0005524), translation factor activity, RNA binding (GO:0008135), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), eukaryotic translation initiation factor 4F complex (GO:0016281), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), nuclear stress granule (GO:0097165)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cap-dependent Translation Initiation	3
Maternal to zygotic transition (MZT)	2
Antimicrobial mechanism of IFN-stimulated genes	1
Eukaryotic Translation Initiation	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
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	4
cellular anatomical structure	4
translational initiation	3
cytoplasm	3
translation	2
translation factor activity	2
ATP-dependent activity	2
binding	2
cytoplasmic translation	1
formation of translation initiation ternary complex	1
metabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	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
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cytoplasmic ribonucleoprotein granule	1
RNA cap binding complex	1
extracellular vesicle	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

239 interactions, top by confidence:

A	B	Type	Score
EIF4A1	EIF4G1	psi-mi:“MI:0407”(direct interaction)	0.970
EIF4G1	EIF4A1	psi-mi:“MI:0407”(direct interaction)	0.970
EIF4A1	PDCD4	psi-mi:“MI:0407”(direct interaction)	0.950
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
EIF4A1	EIF4G3	psi-mi:“MI:0914”(association)	0.800
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
EIF3G	EIF3F	psi-mi:“MI:0914”(association)	0.730
SUN2	LMNA	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EIF3H	EIF3CL	psi-mi:“MI:0914”(association)	0.670
MAP4K1	HSP90AB1	psi-mi:“MI:0914”(association)	0.670
RBM4	EIF4A1	psi-mi:“MI:0407”(direct interaction)	0.660

BioGRID (577): EIF4A1 (Affinity Capture-MS), EIF4A1 (Affinity Capture-MS), EIF4A1 (Affinity Capture-MS), EIF4A1 (Affinity Capture-MS), EIF4A1 (Affinity Capture-MS), EIF4A1 (Reconstituted Complex), EIF4A1 (Affinity Capture-RNA), EIF4A1 (Affinity Capture-MS), EIF4A1 (Affinity Capture-Western), EIF4A1 (Co-fractionation), EIF4A1 (Co-fractionation), EIF4A1 (Co-fractionation), LAGE3 (Co-fractionation), NFYB (Co-fractionation), EIF4A1 (Affinity Capture-MS)

ESM2 similar proteins: A1C595, A1D071, A2QEN5, A4QU31, A4QVP2, A5A6N4, A5AAE5, A6M931, A6R3R5, A6RJ45, A6S4N4, A7EGL7, A7EM88, B5DG42, B5FZY7, B7ZTW1, P0CQ72, P0CQ73, P38919, P47943, P60842, P60843, Q02748, Q0CAS8, Q0UU86, Q10055, Q10I26, Q1DQ20, Q1DTB3, Q2GWJ5, Q2HFP1, Q2NL22, Q2UAK1, Q3B8Q2, Q3SZ54, Q4IAA0, Q4P184, Q4R3Q1, Q4R8K5, Q4WEB4

Diamond homologs: A1C595, A1CJT5, A1D071, A1D7N3, A2QEN5, A3GFV3, A4QU31, A4QVP2, A5A6N4, A5AAE5, A5DE68, A5DWJ1, A6M931, A6QSQ0, A6R3R5, A6RJ45, A6S4N4, A6ZXY5, A7EGL7, A7EM88, A7TEF4, B5DG42, B5FZY7, B7ZTW1, O42226, P0CQ70, P0CQ71, P0CQ72, P0CQ73, P10630, P27639, P29562, P35683, P38919, P41376, P41377, P41378, P41379, P41380, P41382

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Unii-2ewn8Z05CN	“down-regulates activity”	EIF4A1	“chemical inhibition”
EIF4B	“up-regulates activity”	EIF4A1	binding
EIF4H	“up-regulates activity”	EIF4A1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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	16	23.8×	1e-15
Ribosomal scanning and start codon recognition	16	23.8×	1e-15
Dengue Virus Genome Translation and Replication	9	22.3×	2e-08
Formation of the ternary complex, and subsequently, the 43S complex	12	20.2×	7e-11
L13a-mediated translational silencing of Ceruloplasmin expression	17	13.4×	1e-12
GTP hydrolysis and joining of the 60S ribosomal subunit	17	13.3×	1e-12
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	12.8×	5e-04
Nonsense-Mediated Decay (NMD)	6	10.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	10	73.9×	4e-15
translational initiation	17	40.1×	2e-20
regulation of translational initiation	10	30.8×	2e-10
miRNA-mediated gene silencing by inhibition of translation	5	29.2×	8e-05
stress granule assembly	6	23.8×	2e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	15.4×	2e-03
positive regulation of translation	9	13.5×	6e-06
positive regulation of transcription initiation by RNA polymerase II	6	10.7×	2e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1585 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7574537:A:AG	acceptor_gain	1.0000
17:7574538:T:G	acceptor_gain	1.0000
17:7574544:A:AG	acceptor_gain	1.0000
17:7574544:A:AT	acceptor_loss	1.0000
17:7574544:AG:A	acceptor_loss	1.0000
17:7574545:G:GA	acceptor_gain	1.0000
17:7574545:GA:G	acceptor_gain	1.0000
17:7574545:GAGT:G	acceptor_gain	1.0000
17:7574545:GAGTA:G	acceptor_gain	1.0000
17:7574677:GG:G	donor_gain	1.0000
17:7574678:G:GT	donor_gain	1.0000
17:7575114:TTTA:T	acceptor_loss	1.0000
17:7575115:TTAG:T	acceptor_loss	1.0000
17:7575116:TAG:T	acceptor_loss	1.0000
17:7575117:A:AG	acceptor_gain	1.0000
17:7575118:G:GG	acceptor_gain	1.0000
17:7575118:GGTT:G	acceptor_gain	1.0000
17:7575255:GCAG:G	donor_gain	1.0000
17:7575257:AGG:A	donor_loss	1.0000
17:7575258:GGT:G	donor_loss	1.0000
17:7575259:G:T	donor_loss	1.0000
17:7575260:T:G	donor_loss	1.0000
17:7576517:T:TA	acceptor_gain	1.0000
17:7576521:CA:C	acceptor_loss	1.0000
17:7576522:A:AG	acceptor_gain	1.0000
17:7576523:G:GT	acceptor_gain	1.0000
17:7576523:GA:G	acceptor_gain	1.0000
17:7576523:GAT:G	acceptor_gain	1.0000
17:7576626:G:GT	donor_gain	1.0000
17:7576644:G:GG	donor_gain	1.0000

AlphaMissense

2688 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7574573:T:C	F34L	1.000
17:7574574:T:C	F34S	1.000
17:7574574:T:G	F34C	1.000
17:7574575:T:A	F34L	1.000
17:7574575:T:G	F34L	1.000
17:7574604:T:C	L44P	1.000
17:7574609:G:C	G46R	1.000
17:7574610:G:A	G46D	1.000
17:7574610:G:T	G46V	1.000
17:7574624:G:C	G51R	1.000
17:7574625:G:A	G51D	1.000
17:7574625:G:T	G51V	1.000
17:7574627:T:C	F52L	1.000
17:7574628:T:C	F52S	1.000
17:7574628:T:G	F52C	1.000
17:7574629:T:A	F52L	1.000
17:7574629:T:G	F52L	1.000
17:7574637:C:A	P55H	1.000
17:7574637:C:G	P55R	1.000
17:7574646:T:A	I58N	1.000
17:7574650:G:C	Q59H	1.000
17:7574650:G:T	Q59H	1.000
17:7574652:A:C	Q60P	1.000
17:7574655:G:C	R61P	1.000
17:7574657:G:C	A62P	1.000
17:7574658:C:A	A62D	1.000
17:7575125:A:T	D71V	1.000
17:7575133:G:C	A74P	1.000
17:7575134:C:A	A74D	1.000
17:7575139:G:C	A76P	1.000

dbSNP variants (sampled 300 via entrez): RS1000205759 (17:7578715 A>C,G,T), RS1001040424 (17:7573648 T>A), RS1001530315 (17:7573369 C>T), RS1001568476 (17:7576023 A>AT), RS1001775058 (17:7575480 G>A,T), RS1002210858 (17:7576248 T>C), RS1002627047 (17:7572410 G>A,C,T), RS1002645516 (17:7576555 A>C), RS1002739188 (17:7579174 A>G), RS1003599612 (17:7578763 C>T), RS1004590424 (17:7573187 C>T), RS1004976340 (17:7571847 A>T), RS1005380870 (17:7573191 C>G,T), RS1005411561 (17:7576318 A>G), RS1005597684 (17:7572515 G>A,C,T)

Disease associations

OMIM: gene MIM:602641 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2052028 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,097 (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
CHEMBL123292	CYCLOHEXIMIDE	2	39,732
CHEMBL4303782	ZOTATIFIN	2	365

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

ChEMBL bioactivities

97 potent at pChembl≥5 of 136 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	EC50	0.2	nM	CHEMBL2170713
9.30	IC50	0.5	nM	CHEMBL2058177
9.22	EC50	0.6	nM	CHEMBL2170563
9.10	EC50	0.8	nM	CHEMBL2170562
9.10	EC50	0.8	nM	SILVESTROL
9.05	EC50	0.9	nM	CHEMBL2170556
9.00	EC50	1	nM	CHEMBL2170555
9.00	EC50	1	nM	CHEMBL2170714
9.00	IC50	1	nM	ROCAGLAMIDE
9.00	IC50	1	nM	CHEMBL6177866
8.92	EC50	1.2	nM	CHEMBL2170703
8.82	IC50	1.5	nM	ZOTATIFIN
8.70	EC50	2	nM	CHEMBL2170559
8.64	IC50	2.3	nM	CHEMBL4857096
8.52	EC50	3	nM	CHEMBL2170561
8.52	EC50	3	nM	CHEMBL2170560
8.52	EC50	3	nM	CHEMBL2170722
8.52	EC50	3	nM	CHEMBL2170718
8.52	EC50	3	nM	CHEMBL2170725
8.40	EC50	4	nM	CHEMBL2170713
8.40	EC50	4	nM	CHEMBL2170557
8.33	IC50	4.7	nM	ROCAGLAMIDE
8.30	EC50	5	nM	CHEMBL2170714
8.30	EC50	5	nM	CHEMBL2170558
8.30	IC50	5	nM	CHEMBL4864162
8.25	IC50	5.6	nM	CHEMBL4855528
8.20	IC50	6.3	nM	ZOTATIFIN
8.15	EC50	7	nM	SILVESTROL
8.00	EC50	10	nM	AGLAFOLIN
8.00	EC50	10	nM	CHEMBL2170724
8.00	IC50	10	nM	CHEMBL4849769
7.96	EC50	11	nM	CHEMBL2170709
7.96	IC50	11	nM	CHEMBL4857096
7.86	IC50	13.8	nM	ZOTATIFIN
7.85	EC50	14	nM	CHEMBL2170725
7.82	EC50	15	nM	CHEMBL2170563
7.82	EC50	15	nM	CHEMBL2170556
7.77	EC50	17	nM	CHEMBL2170559
7.72	EC50	19	nM	CHEMBL2170560
7.70	IC50	20	nM	CHEMBL2058177
7.68	Kd	21	nM	ZOTATIFIN
7.68	IC50	21	nM	CHEMBL4864162
7.66	IC50	22	nM	CHEMBL4855528
7.64	EC50	23	nM	CHEMBL2170561
7.62	Kd	24.14	nM	CHEMBL3752910
7.62	ED50	24.14	nM	CHEMBL3752910
7.60	IC50	25	nM	CHEMBL4875109
7.54	EC50	29	nM	CHEMBL2169895
7.52	EC50	30	nM	CHEMBL2170555
7.50	IC50	32	nM	CHEMBL4849769

PubChem BioAssay actives

93 with measured affinity, of 300 total; 42 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
dimethyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2,6-dicarboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0002	uM
(1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-N,6,8-trimethoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	671541: Inhibition of eIF4A1-mediated protein synthesis in human BJAB cells assessed as inhibition of [35S]Met incorporation after 72 hr by scintillation counting	ic50	0.0005	uM
(1R,2R,3S,3aR,8bS)-6-chloro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0006	uM
methyl (1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0008	uM
(1R,2R,3S,3aR,8bS)-6-cyano-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0008	uM
methyl (1R,2R,3S,3aR,8bS)-6-cyano-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0009	uM
methyl (1R,2R,3S,3aR,8bS)-6-acetyl-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0010	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,3R,6S)-6-(2-hydroxyethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0010	uM
(1R,2R,3S,3aR,8bS)-3a-(4-cyanophenyl)-1,8b-dihydroxy-6,8-dimethoxy-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0012	uM
4-[(2S,3R,4S,5S,6R)-4-[(dimethylamino)methyl]-2,3-dihydroxy-10,12-dimethoxy-5-phenyl-7-oxa-11-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-6-yl]benzonitrile	1656113: Inhibition of eIF4A1 in human MDA-MB-231 cells assessed as inhibition of cellular-translation incubated for 4 hrs by specific tandem sequence motif repeat AGAGAG in 5’- UTR containing luciferase reporter gene assay	ic50	0.0015	uM
methyl (1R,2R,3S,3aR,8bS)-3a-(4-cyanophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0020	uM
(2R,3R,4R,5S,6R)-6-(4-bromophenyl)-4-(hydroxymethyl)-12-methoxy-3-[(oxetan-3-ylamino)methyl]-5-phenyl-7-oxa-10-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-2-ol	1777528: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring highly structured 5’-UTR of c-Myc	ic50	0.0023	uM
(1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1S)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0030	uM
(1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,6S)-6-(hydroxymethyl)-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0030	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,6S)-6-(hydroxymethyl)-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0030	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,3R,6S)-6-(hydroxymethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0030	uM
methyl (1R,2R,3S,3aR,8bS)-6-[[(2S,6R)-6-[(1R)-1,2-dihydroxyethyl]-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0030	uM
methyl (1R,2R,3S,3aR,8bS)-6-chloro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0040	uM
(1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	1656113: Inhibition of eIF4A1 in human MDA-MB-231 cells assessed as inhibition of cellular-translation incubated for 4 hrs by specific tandem sequence motif repeat AGAGAG in 5’- UTR containing luciferase reporter gene assay	ic50	0.0047	uM
(2R,3R,5S,6R)-3-(aminomethyl)-6-(4-bromophenyl)-12-methoxy-5-phenyl-7-oxa-10-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-2-ol	1777528: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring highly structured 5’-UTR of c-Myc	ic50	0.0050	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methylphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0050	uM
4-[(2R,3R,5S,6R)-3-(aminomethyl)-2-hydroxy-12-methoxy-5-phenyl-7-oxa-10-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-6-yl]benzonitrile	1777528: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring highly structured 5’-UTR of c-Myc	ic50	0.0056	uM
(2R,3R,4R,5S,6R)-6-(4-bromophenyl)-4-(hydroxymethyl)-12-methoxy-3-(morpholin-4-ylmethyl)-5-phenyl-7-oxa-10-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-2-ol	1777528: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring highly structured 5’-UTR of c-Myc	ic50	0.0100	uM
methyl (1R,2R,3S,3aR,8bS)-1,6,8b-trihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0100	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0100	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-6-(methylamino)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0110	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148304: Binding affinity to human EIF4A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0241	uM
(2R,3R,4R,5S,6R)-3-(aminomethyl)-6-(4-bromophenyl)-4-(hydroxymethyl)-12-methoxy-5-phenyl-7-oxa-10-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-2-ol	1777528: Inhibition of eIF4A (unknown origin) assessed as inhibition of translation of RNA featuring highly structured 5’-UTR of c-Myc	ic50	0.0250	uM
methyl (1R,2R,3S,3aR,8bS)-6-carbamoyl-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0290	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-6-(methylcarbamoyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0350	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,3S,6S)-6-(2-hydroxyethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0350	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2R,3R,6S)-6-(hydroxymethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0350	uM
methyl (1R,2R,3S,3aR,8bS)-6-amino-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0400	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[(2S,6S)-6-(hydroxymethyl)oxan-2-yl]oxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0500	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[(2S,6S)-6-(hydroxymethyl)morpholin-2-yl]oxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.0800	uM
4-[(2R)-2-[(1S,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]piperidine-2,6-dione	1656115: Inhibition of eIF4A1 in human MDA-MB-231 cells assessed as inhibition of cellular-translation incubated for 4 hrs by specific tandem sequence motif repeat CCGCCG in 5’- UTR containing luciferase reporter gene assay	ic50	0.0870	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2R,3S,6S)-6-(2-hydroxyethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.1200	uM
methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6-[[(2S,3S,6S)-6-(hydroxymethyl)-3-methoxy-1,4-dioxan-2-yl]oxy]-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate	704240: Inhibition of eIF4FA in human MDA-MB-231 cells transfected with c-myc- 5’-UTR-luciferase construct assessed as reduction in translation initiation incubated for 24 hrs by differential translation assay	ec50	0.1700	uM
(1S,2S,3’S,4S,6R,7R,8R,9S,11S,12S,13S,16R,18S)-2’,2’,3’,7,9,13-hexamethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,5’-oxolane]-7,11,16-triol	1656116: Inhibition of eIF4A1 in human MDA-MB-231 cells assessed as inhibition of cellular-translation incubated for 4 hrs by specific tandem sequence motif repeat CAACAA in 5’- UTR containing luciferase reporter gene assay	ic50	0.2040	uM
2-[5-(4-butylphenyl)furan-2-yl]-6-nitroquinoline-4-carboxylic acid	1939493: Competitive inhibition of human recombinant N-terminal His6-tagged eIF4A expressed in Escherichia coli BL21 CodonPlus cells using 250 uM ATP and varying concentration of yeast RNA as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured after 1 to 7 hrs by Malachite green ATPase assay	ki	4.2700	uM
6-nitro-2-[5-(4-pentylphenyl)furan-2-yl]quinoline-4-carboxylic acid	1939490: Inhibition of human recombinant N-terminal His6-tagged eIF4A expressed in Escherichia coli BL21 CodonPlus cells using ATP and yeast RNA as substrate preincubated with enzyme for 20 mins followed by susbtrate addition and measured after 4 hrs by Malachite green ATPase assay	ic50	8.7700	uM
6-bromo-2-[5-(4-butylphenyl)furan-2-yl]quinoline-4-carboxylic acid	1939493: Competitive inhibition of human recombinant N-terminal His6-tagged eIF4A expressed in Escherichia coli BL21 CodonPlus cells using 250 uM ATP and varying concentration of yeast RNA as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured after 1 to 7 hrs by Malachite green ATPase assay	ki	9.5900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	affects localization, affects binding, increases reaction, decreases expression, increases activity	3
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, affects expression, affects oxidation, increases abundance	2
Doxorubicin	affects expression, increases expression	2
Lead	affects expression, decreases expression	2
Nickel	increases expression	2
Ozone	affects expression, affects oxidation, increases abundance, affects cotreatment	2
Tobacco Smoke Pollution	affects expression	2
spautin-1	affects localization, affects reaction, increases transport, affects cotreatment, increases degradation (+1 more)	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
geldanamycin	increases degradation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects oxidation, increases abundance, affects cotreatment, affects expression	1
sodium arsenate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ochratoxin A	increases expression	1
butylidenephthalide	decreases expression	1
leupeptin	affects cotreatment, decreases reaction, increases degradation	1
methacrylaldehyde	affects oxidation, increases abundance, affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
aloxistatin	affects cotreatment, decreases reaction, increases degradation	1
pateamine A	affects localization	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1

ChEMBL screening assays

76 unique, capped per target: 76 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226423	Binding	Inhibition of eIF4A interaction with mRNA cap structure in presence of 0.6 mM m7 GDP at 50 uM by chemical cross-linking assay	Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. — Nat Chem Biol

Clinical trials (associated diseases)

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