EIF3A

Summary

EIF3A (eukaryotic translation initiation factor 3 subunit A, HGNC:3271) is a protein-coding gene on chromosome 10q26.11, encoding Eukaryotic translation initiation factor 3 subunit A (Q14152). RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis.

Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; formation of cytoplasmic translation initiation complex; and viral translational termination-reinitiation. Located in cytosol; nucleolus; and nucleoplasm. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 8661 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 217 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003750

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3271
Approved symbol	EIF3A
Name	eukaryotic translation initiation factor 3 subunit A
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Aliases	eIF3-theta, eIF3-p170, KIAA0139, TIF32
Ensembl gene	ENSG00000107581
Ensembl biotype	protein_coding
OMIM	602039
Entrez	8661

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000369144, ENST00000462527, ENST00000929552, ENST00000947787, ENST00000947788, ENST00000947789, ENST00000947790

RefSeq mRNA: 1 — MANE Select: NM_003750 NM_003750

CCDS: CCDS7608

Canonical transcript exons

ENST00000369144 — 22 exons

Exon	Start	End
ENSE00000987840	119073441	119073577
ENSE00000987841	119072890	119073053
ENSE00000987843	119070886	119071085
ENSE00000987844	119069446	119069654
ENSE00000987845	119065399	119065570
ENSE00000987847	119061224	119061328
ENSE00000987848	119060746	119060844
ENSE00000987850	119059602	119059718
ENSE00000987852	119059212	119059397
ENSE00000987855	119056936	119057040
ENSE00000987856	119056740	119056853
ENSE00000987859	119041994	119042772
ENSE00000987860	119038238	119038439
ENSE00001002311	119051199	119051321
ENSE00001002312	119044054	119044142
ENSE00001002314	119050521	119050674
ENSE00001002315	119049801	119049985
ENSE00001448903	119033670	119036268
ENSE00001448907	119080628	119080817
ENSE00003420996	119037119	119037309
ENSE00003493721	119057956	119058303
ENSE00003727501	119073747	119073937

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7632 / max 434.1932, expressed in 1786 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111669	91.8663	1828
111668	6.8375	1746
111647	1.7215	867
111645	1.2851	699
111664	0.9023	546
111649	0.8167	488
111646	0.7119	354
111648	0.4130	212
111670	0.0753	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.24	gold quality
tibia	UBERON:0000979	98.69	gold quality
buccal mucosa cell	CL:0002336	98.59	gold quality
amniotic fluid	UBERON:0000173	98.56	gold quality
epithelium of nasopharynx	UBERON:0001951	98.39	gold quality
gingival epithelium	UBERON:0001949	98.36	gold quality
gingiva	UBERON:0001828	98.23	gold quality
upper leg skin	UBERON:0004262	98.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.20	gold quality
skin of hip	UBERON:0001554	98.10	gold quality
esophagus squamous epithelium	UBERON:0006920	97.98	gold quality
tendon	UBERON:0000043	97.95	gold quality
gluteal muscle	UBERON:0002000	97.85	gold quality
superficial temporal artery	UBERON:0001614	97.82	gold quality
germinal epithelium of ovary	UBERON:0001304	97.81	gold quality
biceps brachii	UBERON:0001507	97.79	gold quality
gastrocnemius	UBERON:0001388	97.78	gold quality
medial globus pallidus	UBERON:0002477	97.78	gold quality
oral cavity	UBERON:0000167	97.75	gold quality
penis	UBERON:0000989	97.75	gold quality
parietal pleura	UBERON:0002400	97.75	gold quality
jejunal mucosa	UBERON:0000399	97.58	gold quality
squamous epithelium	UBERON:0006914	97.56	gold quality
islet of Langerhans	UBERON:0000006	97.53	gold quality
jejunum	UBERON:0002115	97.53	gold quality
pleura	UBERON:0000977	97.52	gold quality
body of pancreas	UBERON:0001150	97.52	gold quality
stromal cell of endometrium	CL:0002255	97.51	gold quality
embryo	UBERON:0000922	97.51	gold quality
muscle of leg	UBERON:0001383	97.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	49.43
E-MTAB-10042	yes	14.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

112 targeting EIF3A, 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-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486

Literature-anchored findings (GeneRIF, showing 40)

• The complex formation of eIF3 and its association with the ribosomes might contribute to increased translation rates during T lymphocyte activation. (PMID:15946946)
• Consequently, eIF3c appears to be involved in NF2 pathogenesis and deserves to be investigated as a prognostic marker for NF2 and target for treatment of NF2 patient tumors (PMID:16497727)
• REVIEW of roles of subunits of eIF3 in regulating translation of specific mRNAs encoding proteins important for cell growth control, and how altered expression may cause cancer and/or affect prognosis (PMID:16829125)
• May play some roles in development and differentiation; decreased eIF3a expression may be a pre-requisite of intestinal epithelial cell differentiation. (PMID:17381544)
• Extensive deletion analyses suggest that three evolutionarily conserved subunits (eIF3a, eIF3b, and eIF3c) and three non-conserved subunits (eIF3e, eIF3f, and eIF3h) comprise the functional core of mammalian eIF3. (PMID:17581632)
• was no difference in the expression of EGFR, p185(erbB-2) or Bcl-2, or in nuclear accumulation of p53 in these IDC from pre- vs. post-menopausal women. (PMID:18568671)
• interaction map allows comparison of free eIF3 with that bound to the hepatitis C virus internal ribosome entry site (HCV-IRES) RNA (PMID:18599441)
• eIF3-Paip1 stabilizes the interaction between PABP and eIF4G, which brings about the circularization of the mRNA. (PMID:18725400)
• eIF3a expression oscillated with cell cycle and peaked in S phase. Reducing eIF3a expression also reduced cell proliferation rate by elongating cell cycle but did not change the cell cycle distribution. (PMID:19327350)
• analysis of the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3 (PMID:20399188)
• some studies have identified eIF3a to be involved in cancer development, while other results indicate that it could provide protection against evolution into higher malignancy.[review] (PMID:20647036)
• Docetaxel could slightly increase the expression of eIF3a mRNA, and eIF3a does not regulate the expression of alpha-tubulin in A549 cells. (PMID:20818067)
• eIF3a plays an important role in regulating the expression of DNA repair proteins. (PMID:21610145)
• conclude that eIF3a has an important role in the CDDP response and in NER activity of NPCs by suppressing the synthesis of NER proteins (PMID:21625209)
• POLR2J interacts with three different subunits of eIF3, eIF3a, eIF3i, and eIF3m. (PMID:22022972)
• Iron promotes the translation initiation of hepatitis C virus by stimulating the expression of eIF3A and La proteins. (PMID:22634302)
• Lung cancer patients carrying rs3740556 A allele tended to have a favorable prognosis after treatment with platinum-based chemotherapy. (PMID:23127338)
• eIF3a regulates RPA2 synthesis by regulating its internal ribosome entry site activity (PMID:23393223)
• NDRG1 is regulated by eukaryotic initiation factor 3a (eIF3a) during cellular stress caused by iron depletion. (PMID:23437357)
• MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3 (PMID:23530232)
• results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans (PMID:23623729)
• Mutations in the RNA-binding motif of subunit eIF3a weaken eIF3 binding to the HCV IRES and the 40S ribosomal subunit, thereby suppressing eIF2-dependent recognition of the start codon. (PMID:23766293)
• eukaryotic initiation factor 3a spectrin domain is the docking site for formation of the a:b:i:g subcomplex (PMID:23921387)
• Taken together, these results show that Neurospora crassa eIF3 provides a tractable system for probing the structure and function of human-like eIF3 in the context of living cells. (PMID:24250809)
• The correct folding of subunits of translation initiation factor eIF3 is mediated by interaction with chaperonin containing TCP-1 (CCT). (PMID:24320561)
• Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. (PMID:24386425)
• The Paip1-eIF3 interaction is impaired by the mTORC1 inhibitors. (PMID:24396066)
• findings suggested altered eIF3a expression closely correlated with p27 status, and the association was of prognostic value for resected NSCLC (PMID:24789280)
• eIF3a and eIF3c control abundance and assembly of the entire eIF3 and thus represent its crucial scaffolding elements critically required for formation of preinitiation complexes. (PMID:24912683)
• Data conclude that eIF3a expression may have a profound effect on the urinary bladder cancer phenotype and, in addition, may serve as a prognostic marker for low grade UBCs. (PMID:25070653)
• At 37 degrees C, P185(HER2) internalized through coated pits and vesicles and concentrated in the endosomes and multivesicular bodies in the cells of both cell lines, as well as in lysosomes in cells BT-474 (PMID:25509353)
• eIF3a SNPs are significantly correlated with platinum-based chemotherapy toxicities in Chinese non-small cell lung carcinoma patients. (PMID:25732572)
• Collybistin forms a complex with mTOR and eIF3 and by sequestering these proteins downregulates mTORC1 signaling and protein synthesis potentially contributing to intellectual disability and autism. (PMID:25898924)
• eIF3 has a role in controlling cell size independently of S6K1-activity (PMID:26172298)
• eIF3a improves ovarian cancer patients’ response to cisplatin-based chemotherapy by down regulating XPC and p27(Kip1). (PMID:26213845)
• eIF3a may function as a novel regulator to modulate hepatic stellate cell activation, potentially through inhibiting the TGF-beta1/Smad3 signaling pathway. (PMID:27262813)
• An association between eukaryotic translation initiation factor 3a (eIF3a) gene rs77382849 polymorphism and susceptibility to gastric cancer was observed in Chinese patients. (PMID:27333287)
• DHX29 and eIF3 cooperate in scanning on structured mRNAs. Our findings support previous genetic data on the role of eIF3 during scanning (PMID:27733651)
• The human eIF3b and octameric eIF3a subunits serve as the nucleation core around which other subunits assemble in an ordered way into two interconnected modules: the yeast-like core and the octamer. (PMID:27924037)
• interaction involves the first FF motif of p190A and the winged helix/PCI domain of eIF3A, is enhanced by serum stimulation and reduced by phosphatase treatment (PMID:28007963)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3s10	ENSDARG00000076815
mus_musculus	Eif3a	ENSMUSG00000024991
rattus_norvegicus	Eif3a	ENSRNOG00000010117
drosophila_melanogaster	eIF3a	FBGN0037249
caenorhabditis_elegans		WBGENE00001209

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit A — Q14152 (reviewed: Q14152)

Alternative names: Eukaryotic translation initiation factor 3 subunit 10, eIF-3-theta, eIF3 p167, eIF3 p180, eIF3 p185

All UniProt accessions (1): Q14152

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding 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. (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation. (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2.

Subunit / interactions. Interacts with EIF4G1. 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, EIF3L and EIF3K. 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. Also interacts with KRT7 and PIWIL2.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated. Phosphorylation is enhanced upon serum stimulation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q14152-1	1	yes
Q14152-2	2

RefSeq proteins (1): NP_003741* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR027512	EIF3A	Family
IPR054711	eIF3a_PCI_TPR-like	Domain

Pfam: PF01399, PF22591

UniProt features (115 total): helix 35, repeat 25, turn 16, modified residue 13, strand 8, region of interest 4, compositionally biased region 3, sequence variant 3, sequence conflict 3, initiator methionine 1, chain 1, domain 1, coiled-coil region 1, splice variant 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
6YBT	ELECTRON MICROSCOPY	6
3J8B	ELECTRON MICROSCOPY	9.3
3J8C	ELECTRON MICROSCOPY	11.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14152-F1	63.62	0.21

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 (13): 68, 492, 584, 881, 882, 895, 949, 1028, 1188, 1198, 1262, 1336, 1364

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: 279 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GRUETZMANN_PANCREATIC_CANCER_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TTTGTAG_MIR520D, TATTATA_MIR374, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, TAL1ALPHAE47_01, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, CHANDRAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (8): formation of cytoplasmic translation initiation complex (GO:0001732), translation reinitiation (GO:0002188), translational initiation (GO:0006413), negative regulation of ERK1 and ERK2 cascade (GO:0070373), IRES-dependent viral translational initiation (GO:0075522), viral translational termination-reinitiation (GO:0075525), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), translation initiation factor activity (GO:0003743), structural molecule activity (GO:0005198), receptor tyrosine kinase binding (GO:0030971), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), microtubule (GO:0005874), postsynaptic density (GO:0014069), membrane (GO:0016020), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), multi-eIF complex (GO:0043614), eukaryotic translation initiation factor 3 complex, eIF3e (GO:0071540), eukaryotic translation initiation factor 3 complex, eIF3m (GO:0071541), protein-containing complex (GO:0032991), organelle (GO:0043226)

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
cellular anatomical structure	5
translational initiation	3
cytoplasm	3
cytoplasmic translational initiation	2
viral process	2
viral translation	2
nuclear lumen	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
eukaryotic translation initiation factor 3 complex	2
protein-RNA complex assembly	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	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
RNA binding	1
translation factor activity	1
molecular_function	1
signaling receptor binding	1
protein tyrosine kinase binding	1
binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
protein-containing complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
asymmetric synapse	1
postsynaptic specialization	1
ribonucleoprotein complex	1
cellular_component	1

Protein interactions and networks

STRING

2731 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3A	EIF3D	O15371	893
EIF3A	EIF3E	P60228	864
EIF3A	EIF3B	P55884	835
EIF3A	ERBB2	P04626	832
EIF3A	EIF3M	Q7L2H7	771
EIF3A	EIF3C	Q99613	767
EIF3A	EVPL	Q92817	764
EIF3A	EIF3H	O15372	735
EIF3A	EIF2S2	P20042	679
EIF3A	GRB2	P29354	674
EIF3A	EIF4A1	P04765	652
EIF3A	EIF5	P55010	648
EIF3A	EIF2S1	P05198	645
EIF3A	EIF3F	O00303	638
EIF3A	EIF3J	O75822	627

IntAct

331 interactions, top by confidence:

A	B	Type	Score
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
EIF3M	EIF3F	psi-mi:“MI:0914”(association)	0.960
EIF3G	EIF3B	psi-mi:“MI:0914”(association)	0.930
EIF3B	EIF3G	psi-mi:“MI:0914”(association)	0.930
EIF3F	EIF3B	psi-mi:“MI:0914”(association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3A	EIF3F	psi-mi:“MI:0914”(association)	0.910
EIF3A	EIF3B	psi-mi:“MI:0915”(physical association)	0.890
EIF3H	EIF3F	psi-mi:“MI:0914”(association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
EIF3A	EIF3C	psi-mi:“MI:0407”(direct interaction)	0.800
EIF3D	EIF3F	psi-mi:“MI:0914”(association)	0.730
EIF3G	EIF3F	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (645): EIF3A (Affinity Capture-Western), EIF3A (Two-hybrid), TFIP11 (Two-hybrid), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Reconstituted Complex), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3A (Reconstituted Complex)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, G3V7Q0, O14795, O35841, O43237, O70585, P23116, P48553, Q0P5J8, Q14152, Q15542, Q1JU68, Q3TLI0, Q3UHE1, Q4R5P6, Q5R660, Q5R7S4, Q5R7U7, Q5RE09, Q5RE70, Q5VSL9, Q5XI83, Q658Y4, Q68E01, Q6IQ26, Q6PAL8, Q6PDL0, Q6TEP1, Q6WKZ8, Q7SYD9, Q7TPD0, Q8BIK4, Q8BWQ6, Q8C079, Q8C092, Q8C9H6, Q8CBY8, Q8IWV8, Q8K400

Diamond homologs: A1CRE5, A1D4A7, A2Q8I1, A2VD00, A4II09, A4RM69, A5DHL9, A5E1T3, A7SK48, A7TL64, A8PKH2, A8WM57, A9V549, B0W6N3, B0XP13, B3LY22, B3P211, B4GDX4, B4I3P3, B4K250, B4KA44, B4M693, B4NIC3, B4PTS9, B4QVI2, B5RUP5, O74760, P0CN42, P0CN43, P23116, P34339, P38249, Q0CUP6, Q14152, Q173M7, Q1DXU0, Q1JU68, Q295G5, Q2H6G4, Q2UKG6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BZW2	“up-regulates activity”	EIF3A	binding
EIF3A	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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	21	32.2×	3e-24
Ribosomal scanning and start codon recognition	20	30.7×	9e-23
Formation of the ternary complex, and subsequently, the 43S complex	17	29.5×	4e-19
Deadenylation of mRNA	6	21.2×	2e-05
L13a-mediated translational silencing of Ceruloplasmin expression	22	17.9×	1e-19
GTP hydrolysis and joining of the 60S ribosomal subunit	21	17.0×	2e-18
M-decay: degradation of maternal mRNAs by maternally stored factors	6	15.8×	1e-04
Formation of a pool of free 40S subunits	17	15.3×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	13	97.4×	8e-23
translational initiation	23	55.0×	2e-32
regulation of translational initiation	9	28.1×	8e-09
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	13.4×	3e-03
negative regulation of translation	7	9.1×	1e-03
DNA damage response	12	4.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	162
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3219 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119036265:CTTA:C	acceptor_gain	1.0000
10:119036266:TTA:T	acceptor_gain	1.0000
10:119036267:TA:T	acceptor_gain	1.0000
10:119036269:C:CC	acceptor_gain	1.0000
10:119036270:T:C	acceptor_loss	1.0000
10:119036277:T:C	acceptor_gain	1.0000
10:119036277:T:TC	acceptor_gain	1.0000
10:119036278:T:C	acceptor_gain	1.0000
10:119036278:T:TC	acceptor_gain	1.0000
10:119036281:A:AC	acceptor_gain	1.0000
10:119036282:T:C	acceptor_gain	1.0000
10:119036282:T:TC	acceptor_gain	1.0000
10:119037096:T:TA	donor_gain	1.0000
10:119037114:TATA:T	donor_loss	1.0000
10:119037116:TA:T	donor_loss	1.0000
10:119037117:A:AT	donor_loss	1.0000
10:119037118:CCTT:C	donor_gain	1.0000
10:119037121:T:A	donor_gain	1.0000
10:119037316:CCATT:C	acceptor_gain	1.0000
10:119037317:C:T	acceptor_gain	1.0000
10:119037317:CATT:C	acceptor_gain	1.0000
10:119037320:T:C	acceptor_gain	1.0000
10:119038232:TCACA:T	donor_loss	1.0000
10:119038233:CACAC:C	donor_loss	1.0000
10:119038234:ACACC:A	donor_loss	1.0000
10:119038436:CCAC:C	acceptor_gain	1.0000
10:119038437:CACC:C	acceptor_gain	1.0000
10:119038448:T:C	acceptor_gain	1.0000
10:119038448:T:TC	acceptor_gain	1.0000
10:119041988:TTTTA:T	donor_loss	1.0000

AlphaMissense

9117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119050589:C:G	R802P	1.000
10:119050590:G:T	R802S	1.000
10:119050601:C:G	R798P	1.000
10:119050602:G:T	R798S	1.000
10:119050613:C:G	R794P	1.000
10:119050625:C:G	R790P	1.000
10:119051272:C:G	R749P	1.000
10:119051291:C:G	A743P	1.000
10:119051299:C:G	R740P	1.000
10:119056753:T:G	Q728P	1.000
10:119056761:C:A	W725C	1.000
10:119056761:C:G	W725C	1.000
10:119056763:A:G	W725R	1.000
10:119056763:A:T	W725R	1.000
10:119056786:T:G	Q717P	1.000
10:119056799:C:G	A713P	1.000
10:119056816:A:C	I707S	1.000
10:119056816:A:G	I707T	1.000
10:119056818:T:A	E706D	1.000
10:119056818:T:G	E706D	1.000
10:119056820:C:T	E706K	1.000
10:119056828:C:G	R703P	1.000
10:119056829:G:C	R703G	1.000
10:119056829:G:T	R703S	1.000
10:119056830:T:A	K702N	1.000
10:119056830:T:G	K702N	1.000
10:119056834:G:T	A701D	1.000
10:119056835:C:G	A701P	1.000
10:119056836:T:A	R700S	1.000
10:119056836:T:G	R700S	1.000

dbSNP variants (sampled 300 via entrez): RS1000146463 (10:119057682 G>A), RS1000218771 (10:119041832 C>A), RS1000219390 (10:119074801 T>G), RS1000227117 (10:119066283 C>A,G,T), RS1000266924 (10:119044776 A>T), RS1000278806 (10:119079781 A>C,G), RS1000287523 (10:119057360 G>A), RS1000294440 (10:119074575 C>G), RS1000321010 (10:119044932 ATT>A), RS1000427843 (10:119038347 T>C), RS1000627207 (10:119073159 C>T), RS1000666884 (10:119080615 A>T), RS1000671703 (10:119062239 A>G,T), RS1000845660 (10:119075253 C>A,G), RS1000857584 (10:119068573 A>C,G)

Disease associations

OMIM: gene MIM:602039 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725010 (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

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

pChembl	Type	Value	Unit	Molecule
7.12	Kd	76.5	nM	CHEMBL5653589
7.12	ED50	76.5	nM	CHEMBL5653589
6.52	IC50	300	nM	MOLIBRESIB
6.27	Kd	535.2	nM	CHEMBL3752910
6.27	ED50	535.2	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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	2148151: Binding affinity to human EIF3A incubated for 45 mins by Kinobead based pull down assay	kd	0.0765	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	2178629: Inhibition of EIF3A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148151: Binding affinity to human EIF3A incubated for 45 mins by Kinobead based pull down assay	kd	0.5352	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
Cisplatin	decreases expression, increases response to substance	3
sodium arsenite	decreases expression, increases activity, increases expression	2
Doxorubicin	increases response to substance, increases expression	2
Hydrogen Peroxide	affects expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
titanium dioxide	increases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
trichostatin A	affects expression	1
cinnamaldehyde	increases metabolic processing	1
hydroxyhydroquinone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
tamibarotene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Ascorbic Acid	decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	affects cotreatment, increases expression	1
Carbamazepine	affects 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
CHEMBL5651193	Binding	Binding affinity to human EIF3A 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.