EIF3G

Summary

EIF3G (eukaryotic translation initiation factor 3 subunit G, HGNC:3274) is a protein-coding gene on chromosome 19p13.2, encoding Eukaryotic translation initiation factor 3 subunit G (O75821). 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 99.9% of cancer cell lines).

This gene encodes a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which is required for initiation of protein translation. An N-terminal caspase cleavage product of the encoded protein may stimulate degradation of DNA. A mutation in this gene is associated with narcolepsy.

Source: NCBI Gene 8666 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_003755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3274
Approved symbol	EIF3G
Name	eukaryotic translation initiation factor 3 subunit G
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	eIF3-delta, eIF3-p44
Ensembl gene	ENSG00000130811
Ensembl biotype	protein_coding
OMIM	603913
Entrez	8666

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000253108, ENST00000587146, ENST00000587168, ENST00000587681, ENST00000587993, ENST00000588709, ENST00000589009, ENST00000589454, ENST00000589674, ENST00000590158, ENST00000590940, ENST00000592485, ENST00000593054, ENST00000593066, ENST00000593095, ENST00000899262, ENST00000899263, ENST00000899264, ENST00000929480, ENST00000929481, ENST00000946252, ENST00000946253, ENST00000946254

RefSeq mRNA: 1 — MANE Select: NM_003755 NM_003755

CCDS: CCDS12227

Canonical transcript exons

ENST00000253108 — 11 exons

Exon	Start	End
ENSE00000896932	10115967	10116074
ENSE00000896934	10116800	10116989
ENSE00002779933	10119840	10119899
ENSE00002848193	10115014	10115129
ENSE00003459563	10115684	10115820
ENSE00003514750	10115479	10115585
ENSE00003558059	10119654	10119700
ENSE00003575962	10118668	10118727
ENSE00003666577	10119088	10119171
ENSE00003670440	10117084	10117188
ENSE00003692032	10118868	10118956

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 182.4124 / max 1180.9271, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179076	166.1595	1828
179075	14.4078	1807
179072	0.9516	568
179073	0.8935	550

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.16	gold quality
body of pancreas	UBERON:0001150	99.14	gold quality
left ovary	UBERON:0002119	99.14	gold quality
left testis	UBERON:0004533	99.09	gold quality
right testis	UBERON:0004534	99.06	gold quality
gastrocnemius	UBERON:0001388	99.05	gold quality
right ovary	UBERON:0002118	99.02	gold quality
muscle of leg	UBERON:0001383	99.01	gold quality
endocervix	UBERON:0000458	98.96	gold quality
body of stomach	UBERON:0001161	98.95	gold quality
calcaneal tendon	UBERON:0003701	98.94	gold quality
body of uterus	UBERON:0009853	98.92	gold quality
skin of leg	UBERON:0001511	98.91	gold quality
mucosa of stomach	UBERON:0001199	98.89	gold quality
parotid gland	UBERON:0001831	98.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.88	gold quality
left uterine tube	UBERON:0001303	98.86	gold quality
skin of abdomen	UBERON:0001416	98.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.80	gold quality
lower esophagus	UBERON:0013473	98.79	gold quality
monocyte	CL:0000576	98.76	gold quality
minor salivary gland	UBERON:0001830	98.72	gold quality
leukocyte	CL:0000738	98.69	gold quality
mononuclear cell	CL:0000842	98.69	gold quality
muscle organ	UBERON:0001630	98.69	gold quality
popliteal artery	UBERON:0002250	98.69	gold quality
tibial artery	UBERON:0007610	98.69	gold quality
skeletal muscle organ	UBERON:0014892	98.69	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	32.62
E-HCAD-9	yes	18.36
E-CURD-46	yes	16.34
E-MTAB-7606	no	1101.79
E-MTAB-6524	no	310.44
E-MTAB-7052	no	216.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting EIF3G, 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-137-3P	99.87	74.74	2401
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• Furthermore, we found that overexpression of DISC1 in SH-SY5Y cells induces the assembly of eIF3- and TIA-1-positive stress granules (SGs), discrete cytoplasmic granules formed in response to environmental stresses. (PMID:16243297)
• AIF overexpression specifically resulted in the activation of caspase-7, thereby amplifying the inhibition of protein (PMID:17094969)
• PELO is subcellularly localized at the actin cytoskeleton, interacts with HAX1, EIF3G and SRPX proteins and that this interaction occurs at the cytoskeleton; this interaction may facilitate PELO to detect and degrade aberrant mRNAs. (PMID:20406461)
• down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET (PMID:22493286)
• Important roles for eIF3g in the translation initiation machinery and in DNA degradation during apoptosis. (PMID:24080033)
• The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. (PMID:25669430)
• An interaction between eIF4A3 and eIF3g drives the internal initiation of translation. (PMID:37811880)
• In vitro reconstitution of SARS-CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g. (PMID:37821106)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3g	ENSDARG00000016889
mus_musculus	Eif3g	ENSMUSG00000070319
rattus_norvegicus	Eif3g	ENSRNOG00000020619
drosophila_melanogaster	eIF3g1	FBGN0029629
drosophila_melanogaster	eIF3g2	FBGN0038796
caenorhabditis_elegans		WBGENE00001230

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit G — O75821 (reviewed: O75821)

Alternative names: Eukaryotic translation initiation factor 3 RNA-binding subunit, Eukaryotic translation initiation factor 3 subunit 4, eIF-3-delta, eIF3 p42, eIF3 p44

All UniProt accessions (8): O75821, K7EL20, K7EL60, K7ENA8, K7ENH0, K7EP16, K7ER90, K7ERL8

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. This subunit can bind 18S rRNA. (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. Interacts (via C-terminus) with AIFM1 (via N-terminus). Interacts with DHX33; the interaction is independent of RNA.

Subcellular location. Cytoplasm. Nucleus. Perinuclear region.

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

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

RefSeq proteins (1): NP_003746* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR017334	eIF3_g	Family
IPR024675	eIF3g_N	Domain
IPR034240	eIF3G_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF12353

UniProt features (28 total): modified residue 8, strand 8, helix 4, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6YBS	ELECTRON MICROSCOPY	3.1
8PJ4	ELECTRON MICROSCOPY	3.2
8XXM	ELECTRON MICROSCOPY	3.2
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
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
9BLN	ELECTRON MICROSCOPY	3.9
7QP6	ELECTRON MICROSCOPY	4.7
5K0Y	ELECTRON MICROSCOPY	5.8
9CPA	ELECTRON MICROSCOPY	6
2CQ0	SOLUTION NMR
2MJC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75821-F1	70.77	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 (8): 42, 189, 223, 264, 8, 11, 38, 41

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: 152 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_HDAC1, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, MODULE_149, GOBP_TRANSLATION, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, LUI_TARGETS_OF_PAX8_PPARG_FUSION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, DAZARD_UV_RESPONSE_CLUSTER_G5

GO Biological Process (5): formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), viral translational termination-reinitiation (GO:0075525), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (4): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), perinuclear region of cytoplasm (GO:0048471)

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	3
cellular anatomical structure	3
cytoplasm	3
binding	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
viral process	1
viral 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
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

2801 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3G	EIF3B	P55884	998
EIF3G	EIF3I	Q13347	998
EIF3G	EIF3C	Q99613	998
EIF3G	EIF3J	O75822	993
EIF3G	EIF3D	O15371	974
EIF3G	EIF5	P55010	924
EIF3G	PAIP1	Q9H074	907
EIF3G	EIF3K	Q9UBQ5	899
EIF3G	EIF3E	P60228	877
EIF3G	EIF3F	O00303	868
EIF3G	EIF3L	Q9Y262	838
EIF3G	A0A0B4J1V8	A0A0B4J1V8	831
EIF3G	P2RY11	Q96G91	812
EIF3G	EIF4A1	P04765	794
EIF3G	EIF1	P41567	787

IntAct

206 interactions, top by confidence:

A	B	Type	Score
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
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3B	EIF3F	psi-mi:“MI:0914”(association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
EIF3G	EIF3I	psi-mi:“MI:0407”(direct interaction)	0.820
EIF3G	EIF3I	psi-mi:“MI:0915”(physical association)	0.820
EIF3A	EIF3G	psi-mi:“MI:0915”(physical association)	0.800
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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EIF3C	EIF3D	psi-mi:“MI:0915”(physical association)	0.670
EIF3G	HTT	psi-mi:“MI:0915”(physical association)	0.670
EIF3G	PELO	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (475): EIF3G (Two-hybrid), FAM9B (Two-hybrid), EIF3I (Affinity Capture-MS), EIF3B (Affinity Capture-MS), EIF3A (Affinity Capture-MS), EIF3H (Affinity Capture-MS), EIF3F (Affinity Capture-MS), EIF3C (Affinity Capture-MS), EIF3M (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3D (Affinity Capture-MS), EIF3E (Affinity Capture-MS), EIF3G (Affinity Capture-Western), EIF3B (Affinity Capture-Western), EIF3A (Affinity Capture-Western)

ESM2 similar proteins: A3GGU2, A5DNX9, A5E1Z4, A6ZZ25, A7SKE9, A7TFW4, A8NS61, A8WLV5, A8XEG9, O43120, O75821, P0CN52, P0CN53, P0CR50, P0CR51, P27692, P35728, P78795, Q04067, Q0JHZ2, Q19706, Q1HE00, Q28CY2, Q3ZC12, Q4P7G1, Q4PGU6, Q54WM4, Q59ZV5, Q5AJS6, Q5ALX3, Q5RK09, Q641B2, Q6BT10, Q6BZG0, Q6C747, Q6CC84, Q6CEW9, Q6CQR6, Q6CWW9, Q6CWX1

Diamond homologs: A0A0R4IEW8, A4QNI8, A8NS61, A8WLV5, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, B5DF91, B8BCZ8, O01671, O04425, O09032, O17310, O61374, O75821, O89086, O97018, P16914, P19339, P19683, P23241, P26378, P28644, P29558, P49310, P60824, P60825, P60826, P70372, P98179, Q04836, Q12926, Q14011, Q14498

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3G	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 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
Formation of the ternary complex, and subsequently, the 43S complex	18	37.7×	2e-22
Ribosomal scanning and start codon recognition	20	37.0×	3e-24
Translation initiation complex formation	19	35.1×	6e-23
GTP hydrolysis and joining of the 60S ribosomal subunit	23	22.4×	6e-23
Formation of a pool of free 40S subunits	20	21.7×	7e-20
L13a-mediated translational silencing of Ceruloplasmin expression	22	21.6×	7e-22
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	18.5×	3e-06
Eukaryotic Translation Initiation	6	18.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	13	112.3×	2e-23
translational initiation	17	46.9×	4e-22
regulation of translational initiation	8	28.8×	6e-08
stress granule assembly	5	23.1×	2e-04
cytoplasmic translation	12	17.1×	2e-09
negative regulation of translation	7	10.6×	4e-04
translation	10	7.9×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1460 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10115473:TCTTA:T	donor_loss	1.0000
19:10115474:CTTAC:C	donor_loss	1.0000
19:10115475:TTACT:T	donor_loss	1.0000
19:10115476:TA:T	donor_loss	1.0000
19:10115477:A:AC	donor_gain	1.0000
19:10115477:AC:A	donor_loss	1.0000
19:10115478:C:CT	donor_gain	1.0000
19:10115478:CTTGG:C	donor_gain	1.0000
19:10115581:AAGCC:A	acceptor_gain	1.0000
19:10115582:AGCC:A	acceptor_gain	1.0000
19:10115584:CC:C	acceptor_gain	1.0000
19:10115585:CC:C	acceptor_gain	1.0000
19:10115586:C:CC	acceptor_gain	1.0000
19:10115587:T:A	acceptor_loss	1.0000
19:10115680:CCA:C	donor_loss	1.0000
19:10115683:C:CT	donor_loss	1.0000
19:10115706:T:TA	donor_gain	1.0000
19:10115711:AG:A	donor_gain	1.0000
19:10115712:G:C	donor_gain	1.0000
19:10115816:GTCGG:G	acceptor_gain	1.0000
19:10115817:TCGG:T	acceptor_gain	1.0000
19:10115818:CGG:C	acceptor_gain	1.0000
19:10115818:CGGC:C	acceptor_gain	1.0000
19:10115819:GG:G	acceptor_gain	1.0000
19:10115820:GC:G	acceptor_loss	1.0000
19:10115821:C:CA	acceptor_loss	1.0000
19:10115821:C:CC	acceptor_gain	1.0000
19:10115823:G:C	acceptor_gain	1.0000
19:10115823:G:GC	acceptor_gain	1.0000
19:10115825:G:C	acceptor_gain	1.0000

AlphaMissense

2110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10115482:G:A	A315V	1.000
19:10115482:G:T	A315D	1.000
19:10115483:C:G	A315P	1.000
19:10115484:C:A	W314C	1.000
19:10115484:C:G	W314C	1.000
19:10115485:C:G	W314S	1.000
19:10115486:A:G	W314R	1.000
19:10115486:A:T	W314R	1.000
19:10115489:C:T	E313K	1.000
19:10115491:A:T	V312D	1.000
19:10115492:C:A	V312F	1.000
19:10115497:A:C	L310R	1.000
19:10115497:A:G	L310P	1.000
19:10115497:A:T	L310H	1.000
19:10115498:G:A	L310F	1.000
19:10115500:A:C	I309S	1.000
19:10115500:A:G	I309T	1.000
19:10115500:A:T	I309N	1.000
19:10115503:A:G	L308P	1.000
19:10115503:A:T	L308H	1.000
19:10115504:G:A	L308F	1.000
19:10115505:G:C	H307Q	1.000
19:10115505:G:T	H307Q	1.000
19:10115506:T:C	H307R	1.000
19:10115506:T:G	H307P	1.000
19:10115507:G:C	H307D	1.000
19:10115509:T:A	D306V	1.000
19:10115510:C:G	D306H	1.000
19:10115512:T:C	Y305C	1.000
19:10115512:T:G	Y305S	1.000

dbSNP variants (sampled 300 via entrez): RS1000422727 (19:10120643 G>A,C), RS1001218919 (19:10121872 A>G), RS1001449988 (19:10120472 G>A), RS1001898267 (19:10120425 T>C,G), RS1002809416 (19:10119121 C>A,T), RS1003144473 (19:10120511 C>T), RS1003217960 (19:10120147 G>A), RS1003246665 (19:10115266 A>G), RS1004675999 (19:10121414 A>C), RS1004893045 (19:10117476 T>C), RS1005097109 (19:10116328 A>G), RS1005174572 (19:10117654 G>A), RS1005326963 (19:10116136 C>T), RS1005666860 (19:10120964 T>C), RS1005735303 (19:10116135 G>A,T)

Disease associations

OMIM: gene MIM:603913 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): narcolepsy-cataplexy syndrome (MONDO:0016158)

Orphanet (1): Narcolepsy type 1 (Orphanet:2073)

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): CHEMBL6067003 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2305795	EIF3G, P2RY11, PPAN-P2RY11		0.00	0

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
8.33	Kd	4.675	nM	CHEMBL3752910
8.33	ED50	4.675	nM	CHEMBL3752910
7.98	Kd	10.45	nM	CHEMBL5653589
7.98	ED50	10.45	nM	CHEMBL5653589

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148146: Binding affinity to human EIF3G incubated for 45 mins by Kinobead based pull down assay	kd	0.0047	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148146: Binding affinity to human EIF3G incubated for 45 mins by Kinobead based pull down assay	kd	0.0104	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Valproic Acid	increases methylation, affects expression	2
FR900359	affects phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
decabromobiphenyl ether	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression, increases activity	1
cobaltous chloride	increases expression	1
ochratoxin A	affects cotreatment, increases expression	1
cupric oxide	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CD 437	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
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Citrinin	affects cotreatment, increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Dinitrochlorobenzene	affects binding	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
CHEMBL5651188	Binding	Binding affinity to human EIF3G 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)

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

Trial	Phase	Status	Title
NCT02637076	PHASE4	COMPLETED	Xyrem and Brain Dopamine in Narcolepsy
NCT01800045	PHASE3	COMPLETED	Pitolisant to Assess Weekly Frequency of Cataplexy Attacks and EDS in Narcoleptic Patients (HARMONY CTP)
NCT02221869	PHASE3	COMPLETED	A Multicenter Study of the Efficacy and Safety of Xyrem With an Open- Label Pharmacokinetic Evaluation and Safety Extension in Pediatric Subjects With Narcolepsy With Cataplexy
NCT02611687	PHASE3	COMPLETED	Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period
NCT03030599	PHASE3	COMPLETED	A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy
NCT05914194	PHASE3	NOT_YET_RECRUITING	A Eight-Week Study of NLS-2 (Mazindol Extended Release) in Participants With Narcolepsy Type 1
NCT06470828	PHASE3	COMPLETED	A Study of TAK-861 for the Treatment of Narcolepsy Type 1
NCT06505031	PHASE3	COMPLETED	A Study of TAK-861 in People With Narcolepsy Type 1
NCT07363720	PHASE3	RECRUITING	A Trial of TAK-861 for the Treatment of Narcolepsy With Cataplexy
NCT07455383	PHASE3	RECRUITING	A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1
NCT07540897	PHASE3	RECRUITING	A Study to Evaluate the Efficacy, Safety and Tolerability of ALKS 2680 in Adults With Narcolepsy Type 1 (Brilliance NT1 - 304)
NCT04026958	PHASE2	COMPLETED	Clarithromycin Mechanisms in Hypersomnia Syndromes
NCT04096560	PHASE2	TERMINATED	A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy
NCT04820842	PHASE2	TERMINATED	A Study of TAK-994 in Adults With Narcolepsy
NCT05055024	PHASE2	COMPLETED	An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy
NCT05687903	PHASE2	COMPLETED	A Study of TAK-861 in Participants With Narcolepsy Type 1
NCT06358950	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 1 (ALKS 2680-201)
NCT06752668	PHASE2	RECRUITING	A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia
NCT06809803	PHASE2	RECRUITING	Extended-release Sodium Oxybate in Children
NCT07096674	PHASE2	RECRUITING	A Long-term Extension Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia
NCT00345800	PHASE1	COMPLETED	Exploratory Clinical Study to Evaluate Sodium Oxybate (Xyrem) on Potential Endocrine Changes
NCT06462404	PHASE1	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of E2086 Compared to Placebo and Active Comparator in Adult Participants With Narcolepsy Type 1
NCT07584434	PHASE1	NOT_YET_RECRUITING	A Phase 1, First-in-human Study of VX-433
NCT05816382	PHASE2/PHASE3	RECRUITING	A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions
NCT06767683	PHASE2/PHASE3	RECRUITING	A Long-Term Study of ALKS 2680 in Subjects With Narcolepsy and Idiopathic Hypersomnia
NCT07598708	PHASE2/PHASE3	NOT_YET_RECRUITING	A Study to Investigate the Effects of Cleminorexton Compared With Placebo in the Treatment of Participants With Central Disorders of Hypersomnolence
NCT03433131	Not specified	NO_LONGER_AVAILABLE	Expanded Access Program to Provide Treatment With Pitolisant to Adult Patients in the U.S. With Excessive Daytime Sleepiness Associated With Narcolepsy With or Without Cataplexy
NCT04306952	Not specified	COMPLETED	Awareness and Self-Compassion Enhancing Narcolepsy Treatment
NCT04419792	Not specified	SUSPENDED	‘A Profile of Physical Performance Variables in an Out-patient Adult Population With Narcolepsy’
NCT04445129	Not specified	COMPLETED	Wake and Sleep State Transitions on a Portable Electroencephalogram (EEG) Device in Narcolepsy Type 1 (NT1) and Healthy Participants
NCT04483310	Not specified	UNKNOWN	Meditation-Relaxation (MR Therapy) for Sleep Paralysis.
NCT05314556	Not specified	COMPLETED	Group Psychotherapy in Narcolepsy Type 1
NCT05375890	Not specified	COMPLETED	Clinical and Neurophysiological Characteristics of Narcolepsy
NCT05460052	Not specified	COMPLETED	Evaluation of the Effectiveness of a Physical Activity Program on the Severity of Narcolepsy
NCT05709873	Not specified	COMPLETED	Narcolepsy Nightmare Study
NCT05967832	Not specified	UNKNOWN	Contribution of 7 Tesla MRI of the Hypothalamus in the Diagnosis of Type 1 Narcolepsy
NCT05983731	Not specified	UNKNOWN	A Pilot Observational Study to Assess the Ability of Continuous ‘Home’ EEG to Accurately Diagnose Narcolepsy and Demonstrate Response to Treatment
NCT06241911	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation in Patients With Narcolepsy Type 1
NCT06251063	Not specified	COMPLETED	Improving Social Relationships for Adolescents With Central Disorders of Hypersomnolence
NCT06292598	Not specified	RECRUITING	Bacterial Translocation and Gut Microbiota in Type 1 Narcolepsy Patients Versus a Control Population