EIF3B

Summary

EIF3B (eukaryotic translation initiation factor 3 subunit B, HGNC:3280) is a protein-coding gene on chromosome 7p22.3, encoding Eukaryotic translation initiation factor 3 subunit B (P55884). 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. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in cytoplasmic stress granule. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 8662 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 219 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001037283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3280
Approved symbol	EIF3B
Name	eukaryotic translation initiation factor 3 subunit B
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	PRT1
Ensembl gene	ENSG00000106263
Ensembl biotype	protein_coding
OMIM	603917
Entrez	8662

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 8 retained_intron

ENST00000360876, ENST00000397011, ENST00000413917, ENST00000431643, ENST00000463026, ENST00000463229, ENST00000465670, ENST00000466199, ENST00000468250, ENST00000468611, ENST00000475415, ENST00000494658, ENST00000899983, ENST00000899984, ENST00000899985, ENST00000922848, ENST00000922849, ENST00000922850, ENST00000922851, ENST00000972192, ENST00000972193, ENST00000972194

RefSeq mRNA: 5 — MANE Select: NM_001037283 NM_001037283, NM_001362791, NM_001362792, NM_001362793, NM_003751

CCDS: CCDS5332

Canonical transcript exons

ENST00000360876 — 19 exons

Exon	Start	End
ENSE00000831523	2366525	2366591
ENSE00000831529	2371777	2371849
ENSE00000831531	2372673	2372795
ENSE00000831533	2374528	2374606
ENSE00000831535	2375389	2375527
ENSE00001356853	2354827	2355420
ENSE00001871926	2380204	2380745
ENSE00003460730	2362645	2362764
ENSE00003481288	2364372	2364529
ENSE00003508402	2378689	2378766
ENSE00003523320	2363632	2363760
ENSE00003532109	2369472	2369682
ENSE00003540325	2376950	2377075
ENSE00003562877	2363070	2363127
ENSE00003616726	2360710	2360902
ENSE00003655739	2366317	2366448
ENSE00003665779	2379134	2379242
ENSE00003672699	2366999	2367045
ENSE00003694678	2379394	2379511

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.5572 / max 993.5390, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76971	99.2912	1827
76970	1.2659	866

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.16	gold quality
skin of abdomen	UBERON:0001416	98.03	gold quality
skin of leg	UBERON:0001511	97.99	gold quality
lower esophagus	UBERON:0013473	97.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.73	gold quality
esophagus	UBERON:0001043	97.53	gold quality
endometrium epithelium	UBERON:0004811	97.49	gold quality
stromal cell of endometrium	CL:0002255	97.39	gold quality
lower esophagus mucosa	UBERON:0035834	97.36	gold quality
left uterine tube	UBERON:0001303	97.35	gold quality
gastrocnemius	UBERON:0001388	97.33	gold quality
ventricular zone	UBERON:0003053	97.33	gold quality
esophagus mucosa	UBERON:0002469	97.30	gold quality
zone of skin	UBERON:0000014	97.28	gold quality
right ovary	UBERON:0002118	97.25	gold quality
smooth muscle tissue	UBERON:0001135	97.17	gold quality
left testis	UBERON:0004533	97.15	gold quality
left ovary	UBERON:0002119	97.12	gold quality
right testis	UBERON:0004534	97.04	gold quality
body of stomach	UBERON:0001161	97.03	gold quality
muscle of leg	UBERON:0001383	97.02	gold quality
parotid gland	UBERON:0001831	96.98	gold quality
pancreas	UBERON:0001264	96.97	gold quality
right uterine tube	UBERON:0001302	96.95	gold quality
gingival epithelium	UBERON:0001949	96.94	gold quality
body of uterus	UBERON:0009853	96.92	gold quality
transverse colon	UBERON:0001157	96.83	gold quality
minor salivary gland	UBERON:0001830	96.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TP53

miRNA regulators (miRDB)

22 targeting EIF3B, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-95-3P	89.95	66.87	81

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• structural analysis of the eIF3b RNA recognition motif and its interaction with eIF3j (PMID:17190833)
• a conserved tryptophan residue in the human eIF3j N-terminal acidic motif (NTA) is held in the helix alpha1 and loop 5 hydrophobic pocket of the human eIF3b RNA recognition motif (RRM) (PMID:20060839)
• Yeast eIF3b exhibits RNA binding activity but huamn eIF3b doesn’t. (PMID:20862284)
• EIF3B promotes the proliferation of U87 human glioblastoma cells and may play an important role in human glioblastoma development. (PMID:22234522)
• eIF3b expression relates to human bladder and prostate cancer prognosis, is required for tumor growth, and thus a candidate therapeutic target. (PMID:23575475)
• Report EIF3B binding within the IRES domain V of the coxsackie virus B3 mutant strain. (PMID:24063684)
• Novel RNA-binding protein P311 binds eIF3b to promote translation of TGF-beta1, TGF-beta2, TGF-beta3. (PMID:25336651)
• eIF3 has a role in controlling cell size independently of S6K1-activity (PMID:26172298)
• Study demonstrated that EIF3B expression was up-regulated in esophageal squamous cell carcinoma cells and negatively correlated with the prognosis of patients. (PMID:27270324)
• 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)
• EIF3B overexpression correlates with advanced disease conditions and poor prognosis, and it promotes cells proliferation while inhibits cells apoptosis in NSCLC. (PMID:30198870)
• Inhibition of EIF3B gene expression significantly inhibit the proliferation of ovarian cancer cells and increase the apoptosis of ovarian cancer cells. (PMID:30551537)
• High EIF3B expression is associated with cervical cancer. (PMID:31322539)
• Downregulation of eukaryotic translation initiation factor 3b inhibited proliferation and metastasis of gastric cancer. (PMID:31423012)
• Eukaryotic translation initiation factor 3 subunit b is a novel oncogenic factor in prostate cancer. (PMID:32556998)
• EIF3B Associates with Exacerbated Clinical Features, Poor Treatment Response and Survival in Adult Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Patients. (PMID:34617851)
• Eukaryotic translation initiation factor 3 subunit B could serve as a potential prognostic predictor for breast cancer. (PMID:35040374)
• EIF3B stabilizes PTGS2 expression by counteracting MDM2-mediated ubiquitination to promote the development and progression of malignant melanoma. (PMID:36050601)
• EIF3B stabilizes PCNA by counteracting SYVN1-mediated ubiquitination to serve as a promotor in cholangiocarcinoma. (PMID:38687509)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3ba	ENSDARG00000059654
danio_rerio	eif3bb	ENSDARG00000074213
mus_musculus	Eif3b	ENSMUSG00000056076
rattus_norvegicus	Eif3b	ENSRNOG00000001253
drosophila_melanogaster	eIF3b	FBGN0034237
caenorhabditis_elegans		WBGENE00001225

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit B — P55884 (reviewed: P55884)

Alternative names: Eukaryotic translation initiation factor 3 subunit 9, Prt1 homolog, eIF-3-eta, eIF3 p110, eIF3 p116

All UniProt accessions (3): P55884, C9JQN7, C9JZG1

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) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2.

Subunit / interactions. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Also interacts with UPF2 and HNRPD. Interacts with METTL3. Interacts with DDX3X.

Subcellular location. Cytoplasm. Stress granule.

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

Domain organisation. The RRM domain mediates interaction with EIF3J.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P55884-1	1	yes
P55884-2	2

RefSeq proteins (5): NP_001032360, NP_001349720, NP_001349721, NP_001349722, NP_003742 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR011400	EIF3B	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013979	TIF_beta_prop-like	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR034363	eIF3B_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF08662

UniProt features (44 total): modified residue 14, repeat 8, strand 6, compositionally biased region 4, region of interest 3, sequence variant 2, helix 2, chain 1, domain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6ZON	ELECTRON MICROSCOPY	3
8PJ4	ELECTRON MICROSCOPY	3.2
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	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
5K1H	ELECTRON MICROSCOPY	4.9
6YBT	ELECTRON MICROSCOPY	6
9CPA	ELECTRON MICROSCOPY	6
2KRB	SOLUTION NMR
2NLW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55884-F1	74.64	0.23

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 (14): 1, 78, 81, 83, 85, 119, 125, 152, 154, 164, 209, 239, 288, 364

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: 248 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, chr7p22, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, GTGCCTT_MIR506, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (7): formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), 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), translation initiation factor activity (GO:0003743), translation initiation factor binding (GO:0031369), molecular adaptor activity (GO:0060090), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (9): cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), cytoplasmic stress granule (GO:0010494), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), synapse (GO:0045202), extracellular exosome (GO:0070062), eukaryotic translation initiation factor 3 complex, eIF3m (GO:0071541), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	4
binding	3
viral process	2
viral translation	2
cytoplasm	2
cellular anatomical structure	2
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
regulation of translation	1
cytoplasmic translation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
translation factor activity	1
protein binding	1
molecular_function	1
protein-containing complex	1
cytoplasmic ribonucleoprotein granule	1
cell junction	1
extracellular vesicle	1
eukaryotic translation initiation factor 3 complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3B	EIF3C	Q99613	999
EIF3B	EIF3I	Q13347	999
EIF3B	EIF3G	O75821	998
EIF3B	EIF3J	O75822	998
EIF3B	EIF3D	O15371	992
EIF3B	EIF3E	P60228	991
EIF3B	EIF3H	O15372	985
EIF3B	EIF3F	O00303	984
EIF3B	G3BP1	Q13283	967
EIF3B	EIF2S1	P05198	937
EIF3B	EIF4G1	Q04637	937
EIF3B	EIF3M	Q7L2H7	928
EIF3B	YTHDF1	Q9BYJ9	928
EIF3B	EIF4E	P06730	927
EIF3B	EIF1	P41567	876

IntAct

255 interactions, top by confidence:

A	B	Type	Score
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
EIF3G	EIF3B	psi-mi:“MI:0914”(association)	0.930
EIF3B	EIF3G	psi-mi:“MI:0407”(direct interaction)	0.930
EIF3B	EIF3G	psi-mi:“MI:0915”(physical association)	0.930
EIF3B	EIF3G	psi-mi:“MI:0914”(association)	0.930
EIF3F	EIF3B	psi-mi:“MI:0914”(association)	0.920
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3A	EIF3B	psi-mi:“MI:0915”(physical association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
EIF3B	EIF3H	psi-mi:“MI:0915”(physical association)	0.830
EIF3B	EIF3I	psi-mi:“MI:0915”(physical association)	0.830
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
EIF3B	EIF3E	psi-mi:“MI:0915”(physical association)	0.780
EIF3G	EIF3F	psi-mi:“MI:0914”(association)	0.730
EIF3D	EIF3F	psi-mi:“MI:0914”(association)	0.730
EIF3G	EIF3H	psi-mi:“MI:0914”(association)	0.730

BioGRID (653): RPS6KB1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), NCBP1 (Affinity Capture-Western), EIF4E (Affinity Capture-Western), EIF3B (Affinity Capture-Western), EIF3B (Affinity Capture-Western), EIF3B (Affinity Capture-RNA), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3B (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A2AWP8, A4K436, A5D7H2, A6QLH6, A7MB16, O00291, O08908, O14908, O43237, P55884, P58405, Q13033, Q16512, Q28FH2, Q4G061, Q4R5P6, Q561M0, Q5M9F8, Q5R5M3, Q5R812, Q5RB75, Q5RE09, Q5RE34, Q5VZK9, Q5XIS9, Q63788, Q6EDY6, Q6P6Y1, Q6PDL0, Q86UE8, Q8BZ03, Q8CFE4, Q8IVD9, Q8JZQ9, Q8R1N4, Q8R1T1, Q8WUX9, Q91W86, Q96KG9

Diamond homologs: A1CS92, A1D558, A2Q908, A3LY29, A4QZL9, A5DR43, A5E5Y8, A6SFQ6, A6ZPJ1, A7EHM8, A7MB16, A7TKF2, B0W562, B0XRG7, B3ME25, B3NMI5, B4GAY7, B4HMV9, B4J6D5, B4KNN9, B4LM71, B4MQL8, B4P5F7, B4QB88, B5E081, P06103, P0CN44, P0CN45, P12806, P55884, P56821, Q0CN46, Q0E940, Q0IEY3, Q10425, Q1DI97, Q1HDZ5, Q2GM53, Q2URB7, Q4G061

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3B	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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	22	36.4×	4e-27
Ribosomal scanning and start codon recognition	22	36.4×	4e-27
Formation of the ternary complex, and subsequently, the 43S complex	19	35.6×	3e-23
L13a-mediated translational silencing of Ceruloplasmin expression	24	21.1×	2e-23
GTP hydrolysis and joining of the 60S ribosomal subunit	24	20.9×	2e-23
Deadenylation of mRNA	5	19.1×	2e-04
Formation of a pool of free 40S subunits	19	18.5×	2e-17
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	16.6×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	14	111.5×	3e-26
translational initiation	20	50.9×	6e-27
regulation of translational initiation	7	23.2×	4e-06
stress granule assembly	5	21.3×	4e-04
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	6	19.9×	7e-05
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	14.2×	2e-03
cytoplasmic translation	10	13.1×	2e-06
negative regulation of translation	8	11.1×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	142
Likely benign	4
Benign	30

Top pathogenic / likely-pathogenic (0)

SpliceAI

2928 predictions. Top by Δscore:

Variant	Effect	Δscore
7:2355416:GGAAG:G	donor_gain	1.0000
7:2355417:G:GT	donor_gain	1.0000
7:2355418:A:T	donor_gain	1.0000
7:2355421:G:A	donor_loss	1.0000
7:2355422:T:A	donor_loss	1.0000
7:2360703:T:A	acceptor_gain	1.0000
7:2360705:TTCA:T	acceptor_loss	1.0000
7:2360706:TCA:T	acceptor_loss	1.0000
7:2360708:A:AC	acceptor_loss	1.0000
7:2360708:A:AG	acceptor_gain	1.0000
7:2360709:G:GG	acceptor_gain	1.0000
7:2360709:GA:G	acceptor_gain	1.0000
7:2360709:GAA:G	acceptor_gain	1.0000
7:2360709:GAAT:G	acceptor_gain	1.0000
7:2360709:GAATT:G	acceptor_gain	1.0000
7:2360899:AAGG:A	donor_gain	1.0000
7:2360900:AGG:A	donor_gain	1.0000
7:2360901:GG:G	donor_gain	1.0000
7:2360901:GGG:G	donor_gain	1.0000
7:2360901:GGGT:G	donor_loss	1.0000
7:2360902:GG:G	donor_gain	1.0000
7:2360902:GGT:G	donor_loss	1.0000
7:2360903:G:C	donor_loss	1.0000
7:2360903:G:GG	donor_gain	1.0000
7:2362644:GGT:G	acceptor_gain	1.0000
7:2362644:GGTAT:G	acceptor_gain	1.0000
7:2362760:GACAA:G	donor_gain	1.0000
7:2362762:CAA:C	donor_gain	1.0000
7:2362763:AAGT:A	donor_loss	1.0000
7:2362764:AG:A	donor_loss	1.0000

AlphaMissense

5423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:2360773:T:A	V188E	1.000
7:2360776:T:A	V189E	1.000
7:2360785:T:A	V192D	1.000
7:2360787:C:T	P193S	1.000
7:2360788:C:A	P193H	1.000
7:2360806:G:C	R199P	1.000
7:2360814:A:G	K202E	1.000
7:2360818:T:A	L203H	1.000
7:2360818:T:C	L203P	1.000
7:2360827:T:A	V206D	1.000
7:2360835:A:G	K209E	1.000
7:2362680:C:A	A243D	1.000
7:2362689:C:A	A246D	1.000
7:2362716:T:A	L255H	1.000
7:2362716:T:C	L255P	1.000
7:2362718:G:C	D256H	1.000
7:2362719:A:T	D256V	1.000
7:2362721:A:G	K257E	1.000
7:2362727:C:G	H259D	1.000
7:2362728:A:C	H259P	1.000
7:2362729:C:A	H259Q	1.000
7:2362729:C:G	H259Q	1.000
7:2362740:T:A	V263D	1.000
7:2363680:A:C	S307R	1.000
7:2363682:T:A	S307R	1.000
7:2363682:T:G	S307R	1.000
7:2363714:T:A	I318K	1.000
7:2363714:T:G	I318R	1.000
7:2363756:G:C	R332T	1.000
7:2363757:A:C	R332S	1.000

dbSNP variants (sampled 300 via entrez): RS1000131695 (7:2361936 C>G,T), RS1000292747 (7:2361754 C>T), RS1000361254 (7:2369053 C>G,T), RS1000569310 (7:2352884 T>C), RS1000572141 (7:2353252 T>A,C), RS1000616441 (7:2360357 G>A), RS1000804554 (7:2372318 C>G), RS1000832233 (7:2374252 C>A), RS1000936313 (7:2374090 G>A), RS1000952164 (7:2368092 C>A), RS1001105326 (7:2363479 A>G), RS1001105417 (7:2370725 G>A), RS1001187213 (7:2357501 G>T), RS1001293029 (7:2353457 A>G), RS1001299308 (7:2372497 T>C)

Disease associations

OMIM: gene MIM:603917 | 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
GCST005759_5	Dimensional psychopathology (Social)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009100	social domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066518 (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
8.71	Kd	1.946	nM	CHEMBL5653589
8.71	ED50	1.946	nM	CHEMBL5653589
5.01	Kd	9872	nM	CHEMBL3752910
5.01	ED50	9872	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 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	2148152: Binding affinity to human EIF3B incubated for 45 mins by Kinobead based pull down assay	kd	0.0019	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148152: Binding affinity to human EIF3B incubated for 45 mins by Kinobead based pull down assay	kd	9.8717	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects binding, increases reaction, decreases expression	4
bisphenol A	increases expression, decreases expression	3
Estradiol	decreases phosphorylation, increases expression	3
Caffeine	decreases expression, decreases phosphorylation	2
Lead	affects expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases reaction, decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression, increases expression	1
deoxynivalenol	increases expression	1
manganese chloride	decreases expression, increases abundance	1
cupric oxide	decreases phosphorylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
K 7174	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 B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases phosphorylation	1
bisphenol S	decreases methylation	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651194	Binding	Binding affinity to human EIF3B 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.