EIF3L

Summary

EIF3L (eukaryotic translation initiation factor 3 subunit L, HGNC:18138) is a protein-coding gene on chromosome 22q13.1, encoding Eukaryotic translation initiation factor 3 subunit L (Q9Y262). 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 selective cancer dependency (DepMap: 35.3% of cell lines).

Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in translational initiation and viral translational termination-reinitiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex.

Source: NCBI Gene 51386 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 35.3% of screened cell lines
• MANE Select transcript: NM_016091

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18138
Approved symbol	EIF3L
Name	eukaryotic translation initiation factor 3 subunit L
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC021, HSPC025, EIF3S11
Ensembl gene	ENSG00000100129
Ensembl biotype	protein_coding
OMIM	619197
Entrez	51386

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000381683, ENST00000406934, ENST00000412331, ENST00000414316, ENST00000436452, ENST00000439997, ENST00000450376, ENST00000451427, ENST00000460638, ENST00000464790, ENST00000476955, ENST00000477256, ENST00000482600, ENST00000624234, ENST00000652021

RefSeq mRNA: 3 — MANE Select: NM_016091 NM_001242923, NM_001363785, NM_016091

CCDS: CCDS13960, CCDS56230, CCDS87024

Canonical transcript exons

ENST00000652021 — 13 exons

Exon	Start	End
ENSE00003497350	37863272	37863345
ENSE00003615630	37862969	37863038
ENSE00003694876	37877674	37878171
ENSE00003696834	37875841	37876011
ENSE00003697974	37850015	37850063
ENSE00003698299	37858679	37858740
ENSE00003699261	37855565	37855644
ENSE00003700721	37874370	37874524
ENSE00003701419	37851280	37851490
ENSE00003701477	37870176	37870347
ENSE00003702410	37886765	37886845
ENSE00003851116	37849419	37849482
ENSE00003891302	37888426	37889407

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 351.7968 / max 6704.9331, expressed in 1824 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192205	342.5066	1824
192206	5.4184	1697
192207	1.1545	708
192208	1.1149	667
192209	1.0582	508
192212	0.5442	301

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.77	gold quality
ganglionic eminence	UBERON:0004023	99.71	gold quality
ventricular zone	UBERON:0003053	99.63	gold quality
ovary	UBERON:0000992	99.60	gold quality
left ovary	UBERON:0002119	99.60	gold quality
right ovary	UBERON:0002118	99.51	gold quality
colonic epithelium	UBERON:0000397	99.48	gold quality
stromal cell of endometrium	CL:0002255	99.46	gold quality
body of pancreas	UBERON:0001150	99.46	gold quality
granulocyte	CL:0000094	99.44	gold quality
zone of skin	UBERON:0000014	99.44	gold quality
endocervix	UBERON:0000458	99.44	gold quality
skin of abdomen	UBERON:0001416	99.44	gold quality
skin of leg	UBERON:0001511	99.44	gold quality
thyroid gland	UBERON:0002046	99.44	gold quality
body of uterus	UBERON:0009853	99.43	gold quality
fallopian tube	UBERON:0003889	99.42	gold quality
right lobe of thyroid gland	UBERON:0001119	99.41	gold quality
left lobe of thyroid gland	UBERON:0001120	99.41	gold quality
cerebellar cortex	UBERON:0002129	99.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.40	gold quality
cerebellum	UBERON:0002037	99.39	gold quality
cerebellar hemisphere	UBERON:0002245	99.39	gold quality
islet of Langerhans	UBERON:0000006	99.38	gold quality
fundus of stomach	UBERON:0001160	99.38	gold quality
body of stomach	UBERON:0001161	99.38	gold quality
pancreas	UBERON:0001264	99.38	gold quality
lymph node	UBERON:0000029	99.37	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	93.11
E-GEOD-135922	yes	19.33
E-HCAD-1	yes	12.67
E-MTAB-6678	yes	8.17
E-CURD-112	yes	5.00
E-CURD-122	yes	4.84
E-MTAB-7606	no	1785.35
E-MTAB-6108	no	524.38
E-GEOD-125970	no	427.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting EIF3L, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-6747-3P	97.73	64.84	1596

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• These results indicate an interaction of human eIF3L with yellow fever virus NS5 and that eIF3L overexpression facilitates translation, which has potential implications for virus replication. (PMID:23800076)
• Whereas the eIF3c knockdown reduces it, downregulation of eIF3k or eIF3l increases mRNA recruitment, suggesting that the latter subunits possess a regulatory potential. Altogether this study provides new insights into the role of human eIF3 in the initial assembly steps of the translational machinery (PMID:31863585)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3s6ip	ENSDARG00000101082
mus_musculus	Eif3l	ENSMUSG00000033047
rattus_norvegicus	Eif3l	ENSRNOG00000011020
drosophila_melanogaster	eIF3l	FBGN0036258
caenorhabditis_elegans		WBGENE00015407
caenorhabditis_elegans		WBGENE00015920

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit L — Q9Y262 (reviewed: Q9Y262)

Alternative names: Eukaryotic translation initiation factor 3 subunit 6-interacting protein, Eukaryotic translation initiation factor 3 subunit E-interacting protein

All UniProt accessions (8): Q9Y262, B0QY89, B0QY90, C9JHP4, C9K0Q7, H0Y7E6, H7C133, H7C3A0

UniProt curated annotations — full annotation on UniProt →

Function. 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. Interacts with RRN3.

Subcellular location. Cytoplasm.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y262-1	1	yes
Q9Y262-2	2

RefSeq proteins (3): NP_001229852, NP_001350714, NP_057175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019382	eIF3l	Family

Pfam: PF10255

UniProt features (51 total): helix 23, strand 8, sequence conflict 7, turn 5, modified residue 4, initiator methionine 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
8PPL	ELECTRON MICROSCOPY	2.65
6ZP4	ELECTRON MICROSCOPY	2.9
8PJ5	ELECTRON MICROSCOPY	2.9
8PJ6	ELECTRON MICROSCOPY	2.9
6ZON	ELECTRON MICROSCOPY	3
9KZU	ELECTRON MICROSCOPY	3
8PJ4	ELECTRON MICROSCOPY	3.2
9KN5	ELECTRON MICROSCOPY	3.2
9KRP	ELECTRON MICROSCOPY	3.2
6YBD	ELECTRON MICROSCOPY	3.3
9KKF	ELECTRON MICROSCOPY	3.3
9KN6	ELECTRON MICROSCOPY	3.3
9KZX	ELECTRON MICROSCOPY	3.3
8PJ1	ELECTRON MICROSCOPY	3.4
8PJ2	ELECTRON MICROSCOPY	3.4
8RG0	ELECTRON MICROSCOPY	3.4
7A09	ELECTRON MICROSCOPY	3.5
8OZ0	ELECTRON MICROSCOPY	3.5
8XXN	ELECTRON MICROSCOPY	3.6
6ZMW	ELECTRON MICROSCOPY	3.7
7QP7	ELECTRON MICROSCOPY	3.7
8PJ3	ELECTRON MICROSCOPY	3.7
6ZVJ	ELECTRON MICROSCOPY	3.8
9BLN	ELECTRON MICROSCOPY	3.9
7QP6	ELECTRON MICROSCOPY	4.7
6FEC	ELECTRON MICROSCOPY	6.3
3J8B	ELECTRON MICROSCOPY	9.3
3J8C	ELECTRON MICROSCOPY	11.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y262-F1	69.02	0.00

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 (4): 2, 21, 465, 549

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: 185 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GNF2_BNIP2, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_TRANSLATIONAL_INITIATION, KYNG_DNA_DAMAGE_DN, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, GNF2_FBL, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_UP, ELK1_01, GNF2_ST13, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

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 (3): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), protein binding (GO:0005515)

GO Cellular Component (11): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), membrane (GO:0016020), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), synapse (GO:0045202), nucleolus (GO:0005730), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
translational initiation	3
nuclear lumen	2
cytoplasm	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
binding	1
nucleolus	1
protein-containing complex	1
cell junction	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3L	EIF3C	Q99613	959
EIF3L	EIF3K	Q9UBQ5	938
EIF3L	EIF3F	O00303	936
EIF3L	EIF3E	P60228	935
EIF3L	EIF3B	P55884	861
EIF3L	EIF3M	Q7L2H7	855
EIF3L	EIF3G	O75821	838
EIF3L	EIF3I	Q13347	837
EIF3L	EIF3J	O75822	822
EIF3L	EIF3H	O15372	816
EIF3L	EIF3D	O15371	797
EIF3L	EIF5	P55010	589
EIF3L	EIF3A	Q14152	539
EIF3L	EIF1	P41567	523
EIF3L	EIF4G1	Q04637	515

IntAct

256 interactions, top by confidence:

A	B	Type	Score
EIF3L	EIF3K	psi-mi:“MI:0915”(physical association)	0.960
EIF3K	EIF3L	psi-mi:“MI:0915”(physical association)	0.960
EIF3K	EIF3L	psi-mi:“MI:0407”(direct interaction)	0.960
EIF3L	EIF3K	psi-mi:“MI:0407”(direct interaction)	0.960
EIF3M	EIF3F	psi-mi:“MI:0914”(association)	0.960
EIF3B	EIF3F	psi-mi:“MI:0915”(physical association)	0.920
EIF3A	EIF3F	psi-mi:“MI:0915”(physical association)	0.910
EIF3A	EIF3F	psi-mi:“MI:0914”(association)	0.910
EIF3H	EIF3F	psi-mi:“MI:0914”(association)	0.890
EIF3F	EIF3H	psi-mi:“MI:0914”(association)	0.890
EIF3E	EIF3K	psi-mi:“MI:0915”(physical association)	0.880
EIF3L	EIF3E	psi-mi:“MI:0914”(association)	0.860
EIF3E	EIF3L	psi-mi:“MI:0407”(direct interaction)	0.860
EIF3D	EIF3A	psi-mi:“MI:0914”(association)	0.860
EIF3D	EIF3E	psi-mi:“MI:0915”(physical association)	0.850
EIF3C	EIF3E	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (442): EIF3L (Two-hybrid), EIF3L (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3L (Affinity Capture-MS), EIF3L (Two-hybrid), EIF3A (Co-fractionation), EIF3B (Co-fractionation), EIF3C (Co-fractionation), EIF3CL (Co-fractionation), EIF3D (Co-fractionation), EIF3F (Co-fractionation), EIF3G (Co-fractionation)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: A1C690, A1DGW6, A2R7S7, A5A6M4, A6S1A3, A7E5J5, A7SDW5, A8PHP4, A8X419, A9VCY6, B0WR18, B0XS74, B3M7W0, B3NH71, B4GR63, B4HFJ3, B4IWN1, B4KZ45, B4LEJ0, B4MX71, B4PG99, B4QR64, L7HXG6, P0CN56, P0CN57, P0CT08, Q0CPA8, Q0UIU6, Q16FL6, Q1DZB0, Q2H9N4, Q2M0S3, Q2U041, Q3ZCK1, Q4PF85, Q4X1D2, Q5B0H6, Q5F428, Q6CAE9, Q6P878

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EIF3L	“form complex”	EIF3_complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
Ribosomal scanning and start codon recognition	20	38.1×	2e-24
Formation of the ternary complex, and subsequently, the 43S complex	17	36.6×	8e-21
Translation initiation complex formation	19	36.2×	5e-23
GTP hydrolysis and joining of the 60S ribosomal subunit	22	22.0×	8e-22
L13a-mediated translational silencing of Ceruloplasmin expression	21	21.2×	1e-20
Formation of a pool of free 40S subunits	18	20.1×	4e-17
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	16.3×	1e-04
SRP-dependent cotranslational protein targeting to membrane	11	11.0×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	14	127.9×	7e-27
translational initiation	18	52.5×	2e-24
regulation of translational initiation	8	30.4×	5e-08
stress granule assembly	5	24.5×	2e-04
negative regulation of translation	8	12.7×	4e-05
cytoplasmic translation	8	12.0×	5e-05
positive regulation of translation	6	11.1×	1e-03
translation	9	7.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1864 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37849483:G:GA	donor_loss	1.0000
22:37851267:A:AG	acceptor_gain	1.0000
22:37851268:T:G	acceptor_gain	1.0000
22:37851271:A:AG	acceptor_gain	1.0000
22:37851272:A:G	acceptor_gain	1.0000
22:37851279:GGA:G	acceptor_gain	1.0000
22:37851488:CAGGT:C	donor_loss	1.0000
22:37851489:AGG:A	donor_loss	1.0000
22:37851490:GGTAT:G	donor_loss	1.0000
22:37851491:GT:G	donor_loss	1.0000
22:37851492:T:A	donor_loss	1.0000
22:37858739:GT:G	donor_gain	1.0000
22:37863037:TA:T	donor_gain	1.0000
22:37863039:G:GG	donor_gain	1.0000
22:37870172:ACAGT:A	acceptor_loss	1.0000
22:37870173:CA:C	acceptor_loss	1.0000
22:37870174:A:AG	acceptor_gain	1.0000
22:37870174:A:G	acceptor_loss	1.0000
22:37870175:G:C	acceptor_loss	1.0000
22:37870175:G:GT	acceptor_gain	1.0000
22:37870175:GT:G	acceptor_gain	1.0000
22:37870175:GTTT:G	acceptor_gain	1.0000
22:37870175:GTTTC:G	acceptor_gain	1.0000
22:37870346:AGGT:A	donor_loss	1.0000
22:37870347:GGTG:G	donor_loss	1.0000
22:37870348:GTGA:G	donor_loss	1.0000
22:37874364:TTTCA:T	acceptor_loss	1.0000
22:37874365:TTCAG:T	acceptor_loss	1.0000
22:37874366:TCAG:T	acceptor_loss	1.0000
22:37874367:CA:C	acceptor_loss	1.0000

AlphaMissense

3767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37855566:T:A	W99R	1.000
22:37855566:T:C	W99R	1.000
22:37855576:T:C	L102P	1.000
22:37855605:T:A	W112R	1.000
22:37855605:T:C	W112R	1.000
22:37855606:G:C	W112S	1.000
22:37855607:G:C	W112C	1.000
22:37855607:G:T	W112C	1.000
22:37855608:C:T	P113S	1.000
22:37855609:C:A	P113H	1.000
22:37858699:T:G	Y132D	1.000
22:37858705:G:A	E134K	1.000
22:37858717:A:G	R138G	1.000
22:37858718:G:C	R138T	1.000
22:37858718:G:T	R138M	1.000
22:37858719:G:C	R138S	1.000
22:37858719:G:T	R138S	1.000
22:37858729:G:C	A142P	1.000
22:37862991:G:C	R153T	1.000
22:37862991:G:T	R153M	1.000
22:37862992:G:C	R153S	1.000
22:37862992:G:T	R153S	1.000
22:37862999:T:C	S156P	1.000
22:37863000:C:A	S156Y	1.000
22:37863000:C:T	S156F	1.000
22:37863002:T:G	Y157D	1.000
22:37863010:C:A	N159K	1.000
22:37863010:C:G	N159K	1.000
22:37863011:T:C	Y160H	1.000
22:37863015:G:A	C161Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000063270 (22:37864361 G>A), RS1000077762 (22:37879777 T>C), RS1000143606 (22:37861203 G>A), RS1000170134 (22:37857204 G>A), RS1000266017 (22:37856745 G>A), RS1000346417 (22:37885761 G>A), RS1000404223 (22:37875883 T>C), RS1000518037 (22:37868872 C>T), RS1000540639 (22:37855770 A>T), RS1000559504 (22:37860551 T>C), RS1000573460 (22:37855453 C>A,G,T), RS1000788618 (22:37886574 AAAAAG>A), RS1000803562 (22:37861973 A>G), RS1000849350 (22:37850592 A>C,G), RS1000930320 (22:37860831 C>T)

Disease associations

OMIM: gene MIM:619197 | 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
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725121 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.16	Kd	69	nM	MOLIBRESIB
7.15	Kd	71.43	nM	CHEMBL5653589
7.15	ED50	71.43	nM	CHEMBL5653589
6.89	IC50	130	nM	MOLIBRESIB
5.60	Kd	2496	nM	CHEMBL3752910
5.60	ED50	2496	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179165: Binding affinity against EIF3L (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0690	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148141: Binding affinity to human EIF3L incubated for 45 mins by Kinobead based pull down assay	kd	0.0714	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148141: Binding affinity to human EIF3L incubated for 45 mins by Kinobead based pull down assay	kd	2.4958	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	decreases expression, increases abundance	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases 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
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benztropine	affects cotreatment, decreases expression, increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1
Caffeine	affects phosphorylation	1
Cuprizone	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Furaldehyde	affects cotreatment, decreases expression, affects localization, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651183	Binding	Binding affinity to human EIF3L 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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1VX	HAP1 EIF3L (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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