EIF5B

Summary

EIF5B (eukaryotic translation initiation factor 5B, HGNC:30793) is a protein-coding gene on chromosome 2q11.2, encoding Eukaryotic translation initiation factor 5B (O60841). Plays a role in translation initiation. It is a selective cancer dependency (DepMap: 18.4% of cell lines).

Accurate initiation of translation in eukaryotes is complex and requires many factors, some of which are composed of multiple subunits. The process is simpler in prokaryotes which have only three initiation factors (IF1, IF2, IF3). Two of these factors are conserved in eukaryotes: the homolog of IF1 is eIF1A and the homolog of IF2 is eIF5B. This gene encodes eIF5B. Factors eIF1A and eIF5B interact on the ribosome along with other initiation factors and GTP to position the initiation methionine tRNA on the start codon of the mRNA so that translation initiates accurately.

Source: NCBI Gene 9669 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 166 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 18.4% of screened cell lines
• MANE Select transcript: NM_015904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30793
Approved symbol	EIF5B
Name	eukaryotic translation initiation factor 5B
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	IF2, KIAA0741, DKFZp434I036, FLJ10524
Ensembl gene	ENSG00000158417
Ensembl biotype	protein_coding
OMIM	606086
Entrez	9669

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 retained_intron

ENST00000289371, ENST00000470023, ENST00000470868, ENST00000494190, ENST00000856198, ENST00000856199, ENST00000930012, ENST00000930013, ENST00000967997

RefSeq mRNA: 1 — MANE Select: NM_015904 NM_015904

CCDS: CCDS42721

Canonical transcript exons

ENST00000289371 — 24 exons

Exon	Start	End
ENSE00001038777	99364271	99364421
ENSE00001038780	99379318	99379428
ENSE00001038782	99394267	99394398
ENSE00001038785	99392967	99393098
ENSE00001038787	99394719	99394883
ENSE00001038788	99379019	99379126
ENSE00001038789	99360465	99360549
ENSE00001038790	99398748	99398909
ENSE00001038793	99390544	99390705
ENSE00001038798	99361148	99361820
ENSE00001038804	99389718	99389849
ENSE00001038809	99360236	99360361
ENSE00001038811	99376347	99376636
ENSE00001038813	99368493	99368591
ENSE00001038815	99363645	99363862
ENSE00001038816	99394509	99394585
ENSE00001038818	99382159	99382226
ENSE00001038820	99382780	99382921
ENSE00001038821	99369392	99369481
ENSE00001038825	99371656	99371730
ENSE00001072068	99337389	99337589
ENSE00001199799	99399307	99401326
ENSE00003509657	99390219	99390401
ENSE00003688619	99396760	99396898

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.2882 / max 8086.8488, expressed in 1818 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21568	67.2409	1818
21569	4.9952	1237
21574	3.7934	1055
21578	3.7926	992
202319	2.1564	666
21576	1.8117	640
21577	1.1889	348
21575	1.1207	470
21579	0.6801	246
202318	0.6445	247

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.71	gold quality
oocyte	CL:0000023	99.56	gold quality
secondary oocyte	CL:0000655	99.50	gold quality
cervix squamous epithelium	UBERON:0006922	99.15	gold quality
medial globus pallidus	UBERON:0002477	98.88	gold quality
globus pallidus	UBERON:0001875	98.74	gold quality
left ventricle myocardium	UBERON:0006566	98.19	gold quality
gingival epithelium	UBERON:0001949	98.17	gold quality
pericardium	UBERON:0002407	98.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.14	gold quality
cardia of stomach	UBERON:0001162	98.12	gold quality
lateral globus pallidus	UBERON:0002476	98.10	gold quality
vena cava	UBERON:0004087	98.04	gold quality
cranial nerve II	UBERON:0000941	98.01	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.88	gold quality
inferior olivary complex	UBERON:0002127	97.85	gold quality
saphenous vein	UBERON:0007318	97.84	gold quality
superior surface of tongue	UBERON:0007371	97.83	gold quality
pylorus	UBERON:0001166	97.78	gold quality
substantia nigra pars compacta	UBERON:0001965	97.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.52	gold quality
hair follicle	UBERON:0002073	97.48	gold quality
sperm	CL:0000019	97.47	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.44	gold quality
male germ cell	CL:0000015	97.42	gold quality
subthalamic nucleus	UBERON:0001906	97.37	gold quality
tongue	UBERON:0001723	97.36	gold quality
inferior vagus X ganglion	UBERON:0005363	97.35	gold quality
pharyngeal mucosa	UBERON:0000355	97.30	gold quality
medulla oblongata	UBERON:0001896	97.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-13	no	2.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NRF1, STAT3

miRNA regulators (miRDB)

98 targeting EIF5B, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• determination of binding site on eukaryotic initiation factor 1A (PMID:12569173)
• Transfected nuclear factor 2 trans activates the IF2 promoter in a cell line. (PMID:17161026)
• binding of eIF5B might induce conformational changes in both subunits, with ribosomal segments wrapping around the factor (PMID:17568775)
• 3Cpro-mediated cleavage of eIF5B may thus play an accessory role in the shutoff of translation that occurs in enterovirus-infected cells. (PMID:18572216)
• The authors show that the cleavage of initiation factor eIF5B during enteroviral infection, along with the viral internal ribosome entry site, plays a role in mediating viral translation under conditions that are nonpermissive for host cell translation. (PMID:21697471)
• eIF5B overexpression promotes maturation of G0-like immature oocytes and causes cell death, an alternative to G0, in serum-starved THP1 cells. (PMID:25261552)
• results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation; presentation of a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments (PMID:27325746)
• eIF5B promoted hepatocellular carcinoma cell proliferation and migration in vitro and in vivo partly through increasing ASAP1 expression. (PMID:27694689)
• eIF5B silencing provides a negative feedback to deactivate MAPK signaling (PMID:27959964)
• aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency. (PMID:29298419)
• results indicate that in humans, eIF5B displacing eIF2 from Met-tRNAi upon subunit joining may be coupled to eIF1A displacing eIF5 from eIF5B, allowing the eIF5:eIF2-GDP complex to leave the ribosome. (PMID:30211544)
• Data suggest that eIF5B represents a regulatory node, allowing cancer cells to evade apoptosis by promoting the translation of pro-survival proteins from IRES-containing mRNAs. (PMID:30670698)
• Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumour stem cells (BTSCs). (PMID:31671279)
• eIF5B drives integrated stress response-dependent translation of PD-L1 in lung cancer. (PMID:32984844)
• Depletion of eukaryotic initiation factor 5B (eIF5B) reprograms the cellular transcriptome and leads to activation of endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK). (PMID:33123915)
• eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1. (PMID:34525951)
• Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5. (PMID:34923394)
• eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. (PMID:35732735)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef2a.2	ENSDARG00000042065
danio_rerio	eef2a.1	ENSDARG00000042094
mus_musculus	Eif5b	ENSMUSG00000026083
rattus_norvegicus	Eif5b	ENSRNOG00000023356
rattus_norvegicus		ENSRNOG00000085662
caenorhabditis_elegans		WBGENE00009771

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EEFSEC (ENSG00000132394), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EEF1A1 (ENSG00000156508), GFM2 (ENSG00000164347), EEF2 (ENSG00000167658), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), EIF2S3B (ENSG00000180574), GSPT2 (ENSG00000189369)

Protein

Protein identifiers

Eukaryotic translation initiation factor 5B — O60841 (reviewed: O60841)

Alternative names: Translation initiation factor IF-2

All UniProt accessions (1): O60841

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in translation initiation. Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon. Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after formation of the 80S initiation complex. Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes. In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit.

Subunit / interactions. Interacts through its C-terminal domain (CTD) with the CTD of eIF1A (EIF1AX) or with the CTD of EIF5 (mutually exclusive) through a common binding site. Interacts with eIF1A (EIF1AX) from the location of the start codon by the 43S complex until the formation of the 80S complex. Interacts with ANXA5 in a calcium and phospholipid-dependent manner.

Subcellular location. Cytoplasm.

Post-translational modifications. (Microbial infection) Cleaved and inactivated by the protease 3C of poliovirus, Coxsackievirus B3 and Human rhinovirus 14, allowing the virus to shutoff the host cell translation.

Cofactor. Binds 1 monovalent cation per monomer in the active site. Structural cofactor that stabilizes the GTP-bound ‘on’ state. May also act as a transition state stabilizer of the hydrolysis reaction.

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.

RefSeq proteins (1): NP_056988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR005225	Small_GTP-bd	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR015760	TIF_IF2	Family
IPR023115	TIF_IF2_dom3	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029459	EFTU-type	Domain
IPR036925	TIF_IF2_dom3_sf	Homologous_superfamily

Pfam: PF00009, PF11987, PF14578

Enzyme classification (BRENDA):

• EC 3.6.5.3 — protein-synthesizing GTPase (BRENDA: 45 organisms, 101 substrates, 61 inhibitors, 66 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0003–0.27	53
ATP	0.12–0.2	2

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (129 total): strand 32, modified residue 25, compositionally biased region 15, helix 15, mutagenesis site 9, turn 7, region of interest 7, sequence conflict 7, binding site 5, sequence variant 3, chain 1, domain 1, active site 1, site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8PJ5	ELECTRON MICROSCOPY	2.9
7TQL	ELECTRON MICROSCOPY	3.2
8PJ4	ELECTRON MICROSCOPY	3.2
9KRP	ELECTRON MICROSCOPY	3.2
9KN6	ELECTRON MICROSCOPY	3.3
8PJ3	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60841-F1	66.03	0.20

Functional residue map

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

Catalytic / active sites (2): 706; 478–479 ((microbial infection) cleavage; by viral protease 3c of poliovirus, coxsackievirus b3 and human rhinovirus 14)

Ligand- & substrate-binding residues (5): 640–646; 663–665; 756–757; 759–760; 825–826

Post-translational modifications (25): 66, 107, 113, 134, 135, 137, 164, 171, 182, 183, 186, 190, 214, 222, 301, 438, 498, 547, 557, 560 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
640	loss of activity in vivo. retains full activity in vitro.
706	loss of activity; both in vivo and in vitro. loss of eif5b release from the 80s initiation complex, certainly due to los
706	loss of activity in vivo. partial activity in vitro.
759	loss of activity; both in vivo and in vitro.
1105	disruption of contacts with the met-trna acceptor stem; when associated with a-1174.
1174	disruption of contacts with the met-trna acceptor stem; when associated with a-1105.
1188–1189	disruption of contacts with eif1a (eif1ax); when associated with e-1199 and 1218-r-r-1219.
1199	disruption of contacts with eif1a (eif1ax); when associated with 1188-e-e-1189 and 1218-r-r-1219.
1218–1219	disruption of contacts with eif1a (eif1ax); when associated with 1188-e-r-1189 and e-1199.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit

MSigDB gene sets: 194 (showing top): GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_TRANSLATIONAL_INITIATION, GOBP_RIBOSOME_ASSEMBLY, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, MORF_PPP5C

GO Biological Process (4): translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), ribosome assembly (GO:0042255), translation (GO:0006412)

GO Molecular Function (9): tRNA binding (GO:0000049), RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), GTPase activity (GO:0003924), GTP binding (GO:0005525), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cap-dependent Translation Initiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	3
cellular anatomical structure	2
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
regulation of translation	1
ribosome biogenesis	1
membraneless organelle assembly	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
RNA binding	1
nucleic acid binding	1
translation factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
cell junction	1

Protein interactions and networks

STRING

4300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF5B	ATP5IF1	Q9UII2	998
EIF5B	EIF5	P55010	984
EIF5B	HIF1A	Q16665	981
EIF5B	EIF1	P41567	969
EIF5B	ARNT	P27540	956
EIF5B	EPAS1	Q99814	946
EIF5B	EIF4A2	Q14240	919
EIF5B	EIF4A1	P04765	917
EIF5B	EIF4E	P06730	872
EIF5B	TSFM	P43897	851
EIF5B	EIF4B	P23588	824
EIF5B	EIF2D	P41214	813
EIF5B	EIF4G1	Q04637	812
EIF5B	MRRF	Q96E11	810
EIF5B	EGLN1	Q9GZT9	802

IntAct

105 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
EIF5B	GRN	psi-mi:“MI:0915”(physical association)	0.560
EIF5B	PEX1	psi-mi:“MI:0915”(physical association)	0.560
EIF5B	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CDC42SE1	EIF5B	psi-mi:“MI:0914”(association)	0.530
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
EIF5B	ETS1	psi-mi:“MI:0915”(physical association)	0.520
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
EIF1AY	EIF5B	psi-mi:“MI:0407”(direct interaction)	0.440
EIF5B	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
HMMR	EIF5B	psi-mi:“MI:0915”(physical association)	0.400
THRB	EIF5B	psi-mi:“MI:0915”(physical association)	0.400
EIF5B	NUMA1	psi-mi:“MI:0915”(physical association)	0.400
DEGS1	EIF5B	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
NELL1	EIF5B	psi-mi:“MI:0915”(physical association)	0.400
PIH1D1	EIF5B	psi-mi:“MI:0915”(physical association)	0.400
EIF5B	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (258): EIF5B (Affinity Capture-MS), EIF5B (Two-hybrid), EIF5B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), EIF5B (Affinity Capture-MS), EIF5B (Co-fractionation), EIF5B (Co-fractionation), EIF5B (Co-fractionation), EIF5B (Co-fractionation), EIF5B (Co-fractionation), EIF5B (Co-fractionation), EIF5B (Co-fractionation)

ESM2 similar proteins: A0JPQ1, A2BIL7, A2RVJ8, A2Y4R8, A3N0X3, A6H7C9, A7S7F2, A8DZJ1, A9UL78, B0BPQ7, B2GUV7, B8BJV8, F4I2J8, F4IDY7, O60841, O75167, P0C656, P13864, P26358, P31376, Q05D44, Q12830, Q16U25, Q1DI23, Q24K09, Q27746, Q299F9, Q2R837, Q3T8J9, Q568K9, Q5RDE1, Q5S003, Q60DW3, Q69ZW3, Q6CKU6, Q6FRS1, Q6GZS7, Q6Q759, Q758T8, Q7PYQ5

Diamond homologs: A0B8Q6, A1RUX2, A1RXH6, A2BJZ8, A2RD01, A2STM8, A3CSP4, A3DMS0, A3MTU7, A4FZQ3, A4WIK2, A4YCQ5, A5IJ09, A5UJM9, A6URS1, A6UVG0, A6VIS4, A7IAP7, A7Z4T4, A8A8D3, A8AVQ2, A8FDD1, A8MBV9, A9A813, B0R6U5, B1IA80, B1MZH4, B1YCQ7, B2GUV7, B2IME4, B4U1E8, B5E266, B5XHV3, B6YWH3, B7GG75, B8ZM93, B9DPF5, B9DVB7, B9LQL7, C0M8P7

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EIF5B	“up-regulates activity”	Met-tRNA(Met)	relocalization
EIF5B	“down-regulates activity”	“40S cytosolic small ribosomal subunit”	binding
EIF5B	“down-regulates activity”	“60S cytosolic large ribosomal subunit”	binding
EIF5	“up-regulates activity”	EIF5B	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	2
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3769 predictions. Top by Δscore:

Variant	Effect	Δscore
2:99360230:T:G	acceptor_gain	1.0000
2:99360233:A:AG	acceptor_gain	1.0000
2:99360234:A:AT	acceptor_loss	1.0000
2:99360234:A:G	acceptor_gain	1.0000
2:99360235:G:GG	acceptor_gain	1.0000
2:99360235:GC:G	acceptor_gain	1.0000
2:99360235:GCA:G	acceptor_gain	1.0000
2:99360235:GCACC:G	acceptor_gain	1.0000
2:99360354:GACTT:G	donor_gain	1.0000
2:99360357:TTTGA:T	donor_gain	1.0000
2:99360358:TTGA:T	donor_gain	1.0000
2:99360359:TGA:T	donor_gain	1.0000
2:99360359:TGAGT:T	donor_loss	1.0000
2:99360360:GA:G	donor_gain	1.0000
2:99360360:GAG:G	donor_gain	1.0000
2:99360361:AG:A	donor_loss	1.0000
2:99360362:G:GG	donor_gain	1.0000
2:99360362:GTA:G	donor_loss	1.0000
2:99360366:G:GG	donor_gain	1.0000
2:99360461:CTA:C	acceptor_loss	1.0000
2:99360462:TAGTG:T	acceptor_loss	1.0000
2:99360463:A:AG	acceptor_gain	1.0000
2:99360463:AGT:A	acceptor_gain	1.0000
2:99360464:G:GA	acceptor_gain	1.0000
2:99360464:GT:G	acceptor_gain	1.0000
2:99360464:GTG:G	acceptor_gain	1.0000
2:99360464:GTGA:G	acceptor_gain	1.0000
2:99360464:GTGAA:G	acceptor_gain	1.0000
2:99360545:TGAAG:T	donor_loss	1.0000
2:99360546:GAAGG:G	donor_loss	1.0000

AlphaMissense

8164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:99363747:T:A	V341D	1.000
2:99363752:G:C	A343P	1.000
2:99363764:G:C	A347P	1.000
2:99363768:T:C	L348P	1.000
2:99363770:G:C	A349P	1.000
2:99379081:C:G	C635W	1.000
2:99379086:T:C	L637P	1.000
2:99379088:G:A	G638R	1.000
2:99379088:G:C	G638R	1.000
2:99379088:G:T	G638W	1.000
2:99379089:G:A	G638E	1.000
2:99379089:G:T	G638V	1.000
2:99379093:T:A	H639Q	1.000
2:99379093:T:G	H639Q	1.000
2:99379097:G:C	D641H	1.000
2:99379098:A:C	D641A	1.000
2:99379098:A:T	D641V	1.000
2:99379099:C:A	D641E	1.000
2:99379099:C:G	D641E	1.000
2:99379103:G:A	G643R	1.000
2:99379103:G:C	G643R	1.000
2:99379103:G:T	G643W	1.000
2:99379104:G:A	G643E	1.000
2:99379104:G:T	G643V	1.000
2:99379106:A:C	K644Q	1.000
2:99379108:G:C	K644N	1.000
2:99379108:G:T	K644N	1.000
2:99379110:C:T	T645I	1.000
2:99379119:T:C	L648P	1.000
2:99379121:G:C	D649H	1.000

dbSNP variants (sampled 300 via entrez): RS1000005861 (2:99389042 T>C), RS1000036984 (2:99388610 C>T), RS1000099786 (2:99350792 G>A), RS1000172480 (2:99350414 T>C), RS1000240863 (2:99401781 T>C), RS1000315112 (2:99367804 G>C), RS1000374217 (2:99392320 G>A), RS1000432368 (2:99373949 G>C), RS1000455335 (2:99364063 A>G), RS1000459251 (2:99349312 A>C,G), RS1000484693 (2:99374158 G>A,T), RS1000489087 (2:99349044 A>G), RS1000567100 (2:99400933 G>A), RS1000622842 (2:99367512 C>G,T), RS1000631097 (2:99395964 T>C)

Disease associations

OMIM: gene MIM:606086 | 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
GCST001241_13	Bipolar disorder	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105852 (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: 2,741 (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
CHEMBL2103882	TIVANTINIB	3	2,741

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.63	Kd	232	nM	TIVANTINIB

PubChem BioAssay actives

1 with measured affinity, of 178 total; 1 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
(3R,4R)-3-(1-azatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione	1424986: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2320	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Cisplatin	affects reaction, decreases expression	2
Gold	affects binding, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
coumarin	affects phosphorylation	1
cupric oxide	decreases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	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	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991699	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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