EIF4G2

Summary

EIF4G2 (eukaryotic translation initiation factor 4 gamma 2, HGNC:3297) is a protein-coding gene on chromosome 11p15.4, encoding Eukaryotic translation initiation factor 4 gamma 2 (P78344). Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. It is a selective cancer dependency (DepMap: 80.5% of cell lines).

Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by this gene shares similarity with the C-terminal region of eIF4G that contains the binding sites for eIF4A and eIF3; eIF4G, in addition, contains a binding site for eIF4E at the N-terminus. Unlike eIF4G, which supports cap-dependent and independent translation, this gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.

Source: NCBI Gene 1982 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 106 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 80.5% of screened cell lines
• MANE Select transcript: NM_001418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3297
Approved symbol	EIF4G2
Name	eukaryotic translation initiation factor 4 gamma 2
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	DAP5, NAT1, p97
Ensembl gene	ENSG00000110321
Ensembl biotype	protein_coding
OMIM	602325
Entrez	1982

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 14 protein_coding, 9 retained_intron, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000339995, ENST00000396525, ENST00000524932, ENST00000525606, ENST00000525681, ENST00000525972, ENST00000525995, ENST00000526148, ENST00000527015, ENST00000527419, ENST00000527526, ENST00000528562, ENST00000528839, ENST00000530211, ENST00000530564, ENST00000530702, ENST00000531180, ENST00000531416, ENST00000531507, ENST00000531647, ENST00000532082, ENST00000532120, ENST00000532152, ENST00000532349, ENST00000532383, ENST00000532570, ENST00000533485, ENST00000534246, ENST00000534272, ENST00000534470, ENST00000534605

RefSeq mRNA: 3 — MANE Select: NM_001418 NM_001042559, NM_001172705, NM_001418

CCDS: CCDS31428, CCDS41618

Canonical transcript exons

ENST00000339995 — 22 exons

Exon	Start	End
ENSE00000702669	10800090	10800348
ENSE00001591309	10802049	10802209
ENSE00001738872	10803480	10803590
ENSE00001755026	10801661	10801774
ENSE00002152182	10808705	10808926
ENSE00002733129	10807255	10807381
ENSE00003490839	10803030	10803128
ENSE00003520867	10803211	10803294
ENSE00003527127	10804137	10804203
ENSE00003531025	10804287	10804418
ENSE00003542083	10797054	10797881
ENSE00003567431	10800731	10800835
ENSE00003614449	10803899	10804050
ENSE00003624787	10802294	10802435
ENSE00003644073	10800962	10801087
ENSE00003649388	10800432	10800647
ENSE00003660146	10799213	10799424
ENSE00003667558	10805907	10806047
ENSE00003672663	10799552	10799756
ENSE00003687058	10806820	10806885
ENSE00003690813	10804913	10805015
ENSE00003785564	10798992	10799113

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1172.5556 / max 9478.6967, expressed in 1828 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118662	1139.7804	1828
118648	7.2132	1659
118659	4.6711	1468
118644	3.4547	807
118640	2.9665	1463
118656	2.9039	1429
118650	1.8345	1130
118653	1.6792	1101
118657	1.5370	1036
118655	0.8849	506

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	99.84	gold quality
pleura	UBERON:0000977	99.83	gold quality
germinal epithelium of ovary	UBERON:0001304	99.83	gold quality
parietal pleura	UBERON:0002400	99.82	gold quality
gingival epithelium	UBERON:0001949	99.81	gold quality
gingiva	UBERON:0001828	99.75	gold quality
esophagus squamous epithelium	UBERON:0006920	99.74	gold quality
cortical plate	UBERON:0005343	99.72	gold quality
tibia	UBERON:0000979	99.71	gold quality
ganglionic eminence	UBERON:0004023	99.70	gold quality
colonic epithelium	UBERON:0000397	99.69	gold quality
ventricular zone	UBERON:0003053	99.69	gold quality
superficial temporal artery	UBERON:0001614	99.68	gold quality
epithelium of nasopharynx	UBERON:0001951	99.67	gold quality
upper leg skin	UBERON:0004262	99.67	gold quality
amniotic fluid	UBERON:0000173	99.66	gold quality
embryo	UBERON:0000922	99.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.64	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.63	gold quality
secondary oocyte	CL:0000655	99.62	gold quality
palpebral conjunctiva	UBERON:0001812	99.62	gold quality
choroid plexus epithelium	UBERON:0003911	99.62	gold quality
endometrium epithelium	UBERON:0004811	99.62	gold quality
pigmented layer of retina	UBERON:0001782	99.61	gold quality
tonsil	UBERON:0002372	99.61	gold quality
upper arm skin	UBERON:0004263	99.60	gold quality
colonic mucosa	UBERON:0000317	99.57	gold quality
oral cavity	UBERON:0000167	99.56	gold quality
skin of hip	UBERON:0001554	99.56	gold quality
placenta	UBERON:0001987	99.55	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	39.07
E-CURD-122	yes	8.58
E-MTAB-6819	no	3070.80
E-MTAB-9689	no	1102.09
E-MTAB-11011	no	733.11
E-HCAD-5	no	22.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting EIF4G2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-499A-5P	99.98	70.79	1323
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-19B-3P	99.98	75.44	2754
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-19A-3P	99.98	75.33	2762
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-557	99.96	70.01	1640
HSA-LET-7D-5P	99.96	71.76	1632

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Includes the functional analysis of a similar protein in yeast. (PMID:11331597)
• The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins (PMID:11943866)
• proteolytic activity of HIV-1 protease on eIF4GI and eIF4GII and its implications for the translation of mRNAs (PMID:12505164)
• endogenous eIF4GII was phosphorylated by Ca(2+)/calmodulin-dependent protein kinase I (PMID:14507913)
• Cleavage of eIF4GII is induced in cells and in cell extracts by the FMDV leader protease (L(pro)) alone (PMID:15016848)
• Exclusive use of a GUG translation initiation codon is conserved in human, chicken, Xenopus, and zebrafish. (PMID:15718103)
• EIF4G2 transcripts exhibited three different expression patterns, downregulation was found in about 50% of the cases analyzed and EIF4G2 gene transcription was associated with invasive tumors. (PMID:16410684)
• p97 is functionally different from the closely related C-terminal two-thirds of eIF4GI and it can positively promote protein synthesis and cell proliferation. (PMID:16932749)
• Data show that coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5. (PMID:17195095)
• These data indicate that full-length p97 is a translational activator with essential role(s) in unstressed cells, suggesting a reassessment of current models of p97 function. (PMID:17237356)
• Data show that DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis. (PMID:18450493)
• role and regulation of death-associated protein-5 (DAP5/p97/NAT1), a novel inhibitor of translational initiation, in acute promyelocytic leukemia cell differentiation and apoptosis (PMID:18491231)
• Results report the crystal structure of the C-terminal region of DAP5/p97 extending between amino acids 730 and 897. (PMID:18722383)
• eIF4GI does not colocalize with ribosomes in VSV-infected cells, while eIF2alpha locates at perinuclear sites coincident with ribosomes. (PMID:19769989)
• crystallization and preliminary X-ray diffraction analysis of the MIF4G domain of DAP5 is presented. (PMID:20057060)
• crystal structure of C-terminal region (residues 540-897) of p97/EIF4G2 (at 2.0 Angstrom resolution): sequence/structure homology with EIF4G1 (PMID:20544972)
• DAP5/p97 and DAP5/p86 enhanced the translation of the anti-apoptotic protein Bcl-2 and inhibited cisplatin-induced apoptosis (PMID:22555068)
• Multiple isoforms of eIF4GII arise from multiple promoters & alternative splicing events. A non-canonical CUG initiation codon extends the eIF4GII N-terminus. The eIF4GII N-terminus plays an alternative role in initiation factor assembly. (PMID:22909319)
• DAP5, a translation initiation factor shown to positively regulate the translation of various internal ribosome entry sites containing mRNAs, promotes internal ribosome entry site-driven translation of p53 mRNA. (PMID:23318444)
• Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. (PMID:24497838)
• findings provide the first mechanistic insights into the function of DAP5 as a selective regulator of cap-independent translation (PMID:25779044)
• Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. elevated miR-139-5p expression is associated with a favorable outcome in acute myeloid leukemia. (PMID:26165837)
• The Coxsackievirus B3 protease 2A-mediated cleavage of DAP5 results in the production of two truncates that exert differential effects on protein translation of the IRES-containing genes, leading to enhanced host cell death. (PMID:26586572)
• These results indicate that miR-139 is capable of inhibiting chondrocyte proliferation and migration, thus being a possible therapeutic target for OA. The mechanism of miR-139 in chondrocytes may be related to its regulation on EIF4G2 and IGF1R. (PMID:27105918)
• DAP5 knockdown from human ESCs (hESCs) resulted in persistence of pluripotent gene expression, delayed induction of differentiation-associated genes in different cell lineages, and defective embryoid body formation (PMID:27664238)
• Data show that microRNA miR-379 potentiated lung cancer (LCa) chemosensitivity via modulation of cisplatin (CDDP)-induced apoptosis by directly targeting the eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) 3’ UTR. (PMID:28117895)
• Findings suggest a new translational regulatory mechanism for DSCR1.4 expressions and a novel function of DAP5 as a positive regulator of DSCR1.4 mRNA translation induced in soma and axon of hippocampal neurons. (PMID:30718468)
• the present results suggested that circEIF4G2 may be a novel oncogene in CC. Furthermore, circEIF4G2 may promote CC cell growth and migration by sponging miR-218, thus increasing the expression levels of HOXA1. (PMID:30896864)
• Host DAP5, but not the full-length eIF4GI, is required for Coxsackievirus B3 translation of input viral RNA. (PMID:31455634)
• LncRNA SDHAP1 confers paclitaxel resistance of ovarian cancer by regulating EIF4G2 expression via miR-4465. (PMID:32211849)
• 5’-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs. (PMID:32571876)
• MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2. (PMID:32880393)
• MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of hepatocellular carcinoma through the ERK pathway. (PMID:33526055)
• Long non-coding RNA (LncRNA) SNHG7/ Eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) involves in the malignant events of ovarian cancer cells with paclitaxel resistant. (PMID:34709112)
• A DAP5/eIF3d alternate mRNA translation mechanism promotes differentiation and immune suppression by human regulatory T cells. (PMID:34848685)
• Circular RNA-UBE2D2 accelerates the proliferation and metastasis of non-small cell lung cancer cells via modulating microRNA-376a-3p/Eukaryotic Translation Initiation Factor 4gamma2 axis. (PMID:35196197)
• DAP5 drives translation of specific mRNA targets with upstream ORFs in human embryonic stem cells. (PMID:35961752)
• Eukaryotic translation initiation factor eIF4G2 opens novel paths for protein synthesis in development, apoptosis and cell differentiation. (PMID:36547008)
• Translational fidelity screens in mammalian cells reveal eIF3 and eIF4G2 as regulators of start codon selectivity. (PMID:37144468)
• Breast cancer cell mesenchymal transition and metastasis directed by DAP5/eIF3d-mediated selective mRNA translation. (PMID:37314929)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4g2a	ENSDARG00000020377
danio_rerio	eif4g2b	ENSDARG00000057167
mus_musculus	Eif4g2	ENSMUSG00000005610
rattus_norvegicus	Eif4g2	ENSRNOG00000017158
rattus_norvegicus		ENSRNOG00000087779
rattus_norvegicus		ENSRNOG00000089484
drosophila_melanogaster	NAT1	FBGN0010488

Paralogs (2): EIF4G3 (ENSG00000075151), EIF4G1 (ENSG00000114867)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4 gamma 2 — P78344 (reviewed: P78344)

Alternative names: Death-associated protein 5, p97

All UniProt accessions (16): P78344, D3DQV9, E9PKF8, H0Y3P2, H0YCF8, H0YCH5, H0YD77, H0YD99, H0YDC0, H0YE22, H0YE44, H0YE87, H0YEC5, H0YEI7, H0YEN8, H0YEW3

UniProt curated annotations — full annotation on UniProt →

Function. Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases.

Subunit / interactions. Interacts with the serine/threonine protein kinases MKNK1 and MKNK2. Binds EIF4A and EIF3. Interacts with MIF4GD. Interacts with DAZAP2.

Tissue specificity. Ubiquitously expressed in all adult tissues examined, with high levels in skeletal muscle and heart. Also expressed in fetal brain, lung, liver and kidney.

Post-translational modifications. Phosphorylation; hyperphosphorylated during mitosis.

Miscellaneous. This gene has been shown to be extensively edited in the liver of APOBEC1 transgenic animal model. Its aberrant editing could contribute to the potent oncogenesis induced by overexpression of APOBEC1. The aberrant edited sequence, called NAT1, is likely to be a fundamental translational repressor.

Similarity. Belongs to the eukaryotic initiation factor 4G family.

Isoforms (2)

UniProt ID	Names	Canonical?
P78344-1	1	yes
P78344-2	2

RefSeq proteins (3): NP_001036024, NP_001166176, NP_001409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003307	W2_domain	Domain
IPR003890	MIF4G-like_typ-3	Domain
IPR003891	Initiation_fac_eIF4g_MI	Domain
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF02020, PF02847, PF02854

UniProt features (77 total): helix 38, modified residue 11, sequence conflict 10, turn 6, domain 3, strand 2, region of interest 2, chain 1, cross-link 1, splice variant 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9JJ7	X-RAY DIFFRACTION	1.8
3D3M	X-RAY DIFFRACTION	1.9
3L6A	X-RAY DIFFRACTION	2
4IUL	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78344-F1	72.88	0.43

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 (12): 360, 395, 431, 443, 505, 508, 514, 902, 575, 1, 11, 89

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 521 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_BIOLOGICAL_OXIDATIONS, MYOGENIN_Q6, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, MORF_SNRP70, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I

GO Biological Process (8): translational initiation (GO:0006413), regulation of translational initiation (GO:0006446), cell death (GO:0008219), negative regulation of autophagy (GO:0010507), positive regulation of cell growth (GO:0030307), regulation of cell cycle (GO:0051726), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), translation initiation factor activity (GO:0003743), translation factor activity, RNA binding (GO:0008135), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), adherens junction (GO:0005912), membrane (GO:0016020), eukaryotic translation initiation factor 4F complex (GO:0016281)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	3
translational initiation	3
RNA binding	2
translation factor activity	2
cytoplasm	2
cellular anatomical structure	2
formation of translation initiation ternary complex	1
metabolic process	1
regulation of translation	1
cellular process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell cycle	1
regulation of cellular process	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
cell adhesion molecule binding	1
binding	1
cell-cell junction	1
RNA cap binding complex	1

Protein interactions and networks

STRING

3140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4G2	YTHDF3	Q7Z739	994
EIF4G2	EIF4A2	Q14240	987
EIF4G2	EIF4A1	P04765	983
EIF4G2	EIF4E	P06730	983
EIF4G2	MKNK1	Q9BUB5	877
EIF4G2	ATP7A	Q04656	789
EIF4G2	EIF4B	P23588	761
EIF4G2	PABPC1	P11940	738
EIF4G2	EIF3B	P55884	721
EIF4G2	EIF1	P41567	708
EIF4G2	ZNF609	O15014	701
EIF4G2	EIF5	P55010	676
EIF4G2	EIF3M	Q7L2H7	642
EIF4G2	MKNK2	Q9HBH9	619
EIF4G2	EIF3D	O15371	586

IntAct

144 interactions, top by confidence:

A	B	Type	Score
EIF4A1	EIF4G2	psi-mi:“MI:0915”(physical association)	0.850
EIF4A1	EIF4G2	psi-mi:“MI:0407”(direct interaction)	0.850
EIF4G2	EIF4A1	psi-mi:“MI:0407”(direct interaction)	0.850
EIF2S1	EIF2S2	psi-mi:“MI:0403”(colocalization)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
EIF4G2	EIF4A2	psi-mi:“MI:0915”(physical association)	0.590
EIF2S2	EIF4G2	psi-mi:“MI:0915”(physical association)	0.590
EIF4G2	EIF2S2	psi-mi:“MI:0915”(physical association)	0.590
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
EIF4A1	EIF3D	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
HSPB1	EIF4G2	psi-mi:“MI:0915”(physical association)	0.510
EIF4G2	HSPB1	psi-mi:“MI:0915”(physical association)	0.510
EIF4G2	EIF2S1	psi-mi:“MI:0915”(physical association)	0.500
Dlg4	EIF4G2	psi-mi:“MI:0407”(direct interaction)	0.440
EIF4G2	EIF3J	psi-mi:“MI:0915”(physical association)	0.400
RPA2	EIF4G2	psi-mi:“MI:0915”(physical association)	0.370
	EIF4G2	psi-mi:“MI:0915”(physical association)	0.370
SKIL	EIF4G2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (247): EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Two-hybrid), EIF4G2 (Affinity Capture-Western), EIF4G2 (Affinity Capture-RNA), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS), EIF4G2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A6H7I5, B0DOB5, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EGS5, H2KZZ6, O95466, P21575, P23678, P27619, P39052, P39053, P39054, P39055, P48608, P50570, P78344, P79398, Q01968, Q05193, Q08877, Q08DF4, Q15057, Q15172, Q24564, Q2KI89, Q5R629, Q5R7J9, Q5ZK62, Q62448, Q6IVG4, Q6NXC0, Q6ZQK5, Q7SIG6, Q7XPJ0, Q80U19, Q86T65

Diamond homologs: O43432, O73777, P41110, P78344, P79398, Q04637, Q5R7J9, Q62448, Q6NZJ6, Q80XI3, Q95L46, G5CEW6, O82233, Q03387, Q10475, Q41583, Q553R3, Q5Z5Q3, Q6K641, Q76E23, Q84PB3, Q93ZT6, A0A1S3C4H6, B9FXV5, P39935, P39936, Q8W4Q4, Q94BR1, Q9STL9, C7G046, Q98TX3, O80548, Q53EL6, Q5R8S3, Q61823, Q9JID1

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates activity”	EIF4G2	phosphorylation
EIF4G2	“up-regulates activity”	EIF2S2	binding
CDK1	“up-regulates activity”	EIF4G2	phosphorylation
EIF3_complex	“up-regulates activity”	EIF4G2	stabilization
MicroRNA-877-5p	“down-regulates quantity by destabilization”	EIF4G2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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	13	25.5×	7e-13
Ribosomal scanning and start codon recognition	13	25.5×	7e-13
Formation of the ternary complex, and subsequently, the 43S complex	11	24.4×	8e-11
L13a-mediated translational silencing of Ceruloplasmin expression	14	14.6×	8e-11
GTP hydrolysis and joining of the 60S ribosomal subunit	14	14.5×	8e-11
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	14.0×	3e-03
Formation of a pool of free 40S subunits	10	11.5×	2e-06
Regulation of expression of SLITs and ROBOs	8	5.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	7	64.5×	3e-09
translational initiation	11	32.3×	2e-11
regulation of translational initiation	6	23.0×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2517 predictions. Top by Δscore:

Variant	Effect	Δscore
11:10797879:CAC:C	acceptor_gain	1.0000
11:10797881:CCTAT:C	acceptor_loss	1.0000
11:10797882:C:CC	acceptor_gain	1.0000
11:10798988:TTA:T	donor_loss	1.0000
11:10798989:TA:T	donor_loss	1.0000
11:10798990:A:AC	donor_gain	1.0000
11:10798990:AC:A	donor_gain	1.0000
11:10798991:C:CT	donor_gain	1.0000
11:10798991:CC:C	donor_gain	1.0000
11:10798991:CCT:C	donor_gain	1.0000
11:10798991:CCTG:C	donor_gain	1.0000
11:10798991:CCTGG:C	donor_gain	1.0000
11:10799007:G:A	donor_gain	1.0000
11:10799082:A:C	acceptor_gain	1.0000
11:10799109:CATGC:C	acceptor_gain	1.0000
11:10799110:ATGC:A	acceptor_gain	1.0000
11:10799111:TGC:T	acceptor_gain	1.0000
11:10799112:GC:G	acceptor_gain	1.0000
11:10799113:CC:C	acceptor_gain	1.0000
11:10799113:CCTTA:C	acceptor_loss	1.0000
11:10799114:C:CC	acceptor_gain	1.0000
11:10799114:C:T	acceptor_gain	1.0000
11:10799115:T:A	acceptor_loss	1.0000
11:10799115:T:C	acceptor_gain	1.0000
11:10799115:T:TC	acceptor_gain	1.0000
11:10800347:GC:G	acceptor_gain	1.0000
11:10800348:CCT:C	acceptor_gain	1.0000
11:10800349:C:CC	acceptor_gain	1.0000
11:10800350:T:C	acceptor_gain	1.0000
11:10800350:T:TC	acceptor_gain	1.0000

AlphaMissense

6024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:10797850:G:T	A897D	1.000
11:10797851:C:G	A897P	1.000
11:10797858:T:A	L894F	1.000
11:10797858:T:G	L894F	1.000
11:10797859:A:G	L894S	1.000
11:10797861:C:A	W893C	1.000
11:10797861:C:G	W893C	1.000
11:10797863:A:G	W893R	1.000
11:10797863:A:T	W893R	1.000
11:10797868:A:G	L891P	1.000
11:10797868:A:T	L891Q	1.000
11:10797870:C:A	W890C	1.000
11:10797870:C:G	W890C	1.000
11:10797871:C:G	W890S	1.000
11:10797872:A:G	W890R	1.000
11:10797872:A:T	W890R	1.000
11:10798995:G:C	F885L	1.000
11:10798995:G:T	F885L	1.000
11:10798996:A:C	F885C	1.000
11:10798996:A:G	F885S	1.000
11:10798997:A:G	F885L	1.000
11:10799002:G:T	A883D	1.000
11:10799009:C:G	G881R	1.000
11:10799010:T:A	K880N	1.000
11:10799010:T:G	K880N	1.000
11:10799011:T:A	K880I	1.000
11:10799014:C:T	G879E	1.000
11:10799040:T:A	K870N	1.000
11:10799040:T:G	K870N	1.000
11:10799041:T:A	K870I	1.000

dbSNP variants (sampled 300 via entrez): RS1000521772 (11:10800983 A>G), RS1000525421 (11:10799485 C>G), RS1000717749 (11:10809579 C>A), RS1000773385 (11:10809440 C>G,T), RS1000984859 (11:10805446 G>A), RS1001129628 (11:10799345 A>C,G), RS1001246801 (11:10799068 A>G), RS1001323268 (11:10801277 T>C), RS1001863892 (11:10799875 A>T), RS1002008192 (11:10799417 G>C), RS1002294993 (11:10799665 C>T), RS1002362201 (11:10799161 T>A,C), RS1002421696 (11:10809161 C>A,T), RS1002670891 (11:10802535 C>T), RS1002728680 (11:10808140 C>A,G)

Disease associations

OMIM: gene MIM:602325 | 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
GCST009391_802	Metabolite levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010396	sphingomyelin 22:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067400 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Acrolein	increases oxidation, increases abundance, affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, affects expression, affects cotreatment, decreases expression	2
Tretinoin	increases expression, increases reaction, increases localization	2
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
deoxynivalenol	increases expression	1
methylselenic acid	decreases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression, increases activity	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nivalenol	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression	1
CGP 52608	affects binding, increases reaction	1
scriptaid	affects expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
belinostat	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases 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
CHEMBL5651351	Binding	Binding affinity to human EIF4G2 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2WG	Abcam HEK293T EIF4G2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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