EIF4E1B

Summary

EIF4E1B (eukaryotic translation initiation factor 4E family member 1B, HGNC:33179) is a protein-coding gene on chromosome 5q35.2, encoding Eukaryotic translation initiation factor 4E type 1B (A6NMX2). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structure.

Predicted to enable RNA 7-methylguanosine cap binding activity and translation initiation factor activity. Predicted to be involved in translational initiation. Predicted to be located in cytoplasm. Predicted to be part of eukaryotic translation initiation factor 4F complex.

Source: NCBI Gene 253314 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_001099408

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33179
Approved symbol	EIF4E1B
Name	eukaryotic translation initiation factor 4E family member 1B
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36951
Ensembl gene	ENSG00000175766
Ensembl biotype	protein_coding
Entrez	253314

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000318682, ENST00000503895, ENST00000504597, ENST00000505497, ENST00000510473, ENST00000510660, ENST00000512734, ENST00000515458, ENST00000647833, ENST00000862451, ENST00000862452, ENST00000862453

RefSeq mRNA: 2 — MANE Select: NM_001099408 NM_001099408, NM_001375362

CCDS: CCDS47345

Canonical transcript exons

ENST00000318682 — 9 exons

Exon	Start	End
ENSE00001219593	176645866	176646644
ENSE00001531842	176642043	176642165
ENSE00001680717	176630675	176631064
ENSE00003502114	176645377	176645516
ENSE00003543957	176643639	176643734
ENSE00003576184	176643082	176643266
ENSE00003630195	176642710	176642802
ENSE00003630855	176645130	176645243
ENSE00003691685	176644376	176644439

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 76.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0904 / max 14.3536, expressed in 47 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60428	0.0580	30
60429	0.0324	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.97	gold quality
primary visual cortex	UBERON:0002436	76.84	gold quality
prefrontal cortex	UBERON:0000451	76.26	gold quality
frontal cortex	UBERON:0001870	75.50	gold quality
superior frontal gyrus	UBERON:0002661	74.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.39	gold quality
right frontal lobe	UBERON:0002810	74.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.00	gold quality
cerebral cortex	UBERON:0000956	71.47	gold quality
anterior cingulate cortex	UBERON:0009835	70.67	gold quality
cerebellum	UBERON:0002037	70.56	gold quality
cerebellar cortex	UBERON:0002129	70.52	gold quality
cerebellar hemisphere	UBERON:0002245	70.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.06	gold quality
islet of Langerhans	UBERON:0000006	66.95	gold quality
brain	UBERON:0000955	64.01	gold quality
temporal lobe	UBERON:0001871	63.56	gold quality
amygdala	UBERON:0001876	63.27	gold quality
hypothalamus	UBERON:0001898	61.52	gold quality
Ammon’s horn	UBERON:0001954	59.08	gold quality
substantia nigra	UBERON:0002038	58.85	gold quality
pituitary gland	UBERON:0000007	54.63	gold quality
nucleus accumbens	UBERON:0001882	51.81	gold quality
adenohypophysis	UBERON:0002196	51.66	gold quality
putamen	UBERON:0001874	51.23	gold quality
caudate nucleus	UBERON:0001873	51.16	gold quality
pancreas	UBERON:0001264	48.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	47.94	gold quality
cortical plate	UBERON:0005343	46.54	gold quality
colonic epithelium	UBERON:0000397	46.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting EIF4E1B, 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-4779	99.86	66.50	1583
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-1266-3P	96.23	66.36	778

Literature-anchored findings (GeneRIF, showing 1)

• eIF4E1b is a non-canonical eIF4E protecting maternal dormant mRNAs. (PMID:38177902)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4e1b	ENSDARG00000014565
mus_musculus	Eif4e1b	ENSMUSG00000074895
rattus_norvegicus	AC135142.1	ENSRNOG00000025480
drosophila_melanogaster	eIF4E1	FBGN0015218
drosophila_melanogaster	eIF4E4	FBGN0035709
drosophila_melanogaster	eIF4E5	FBGN0035823
drosophila_melanogaster	eIF4E6	FBGN0039622
drosophila_melanogaster	eIF4E7	FBGN0040368
drosophila_melanogaster	eIF4EHP	FBGN0053100
drosophila_melanogaster	eIF4E3	FBGN0265089
caenorhabditis_elegans		WBGENE00002059
caenorhabditis_elegans		WBGENE00002062
caenorhabditis_elegans		WBGENE00002063

Paralogs (3): EIF4E2 (ENSG00000135930), EIF4E (ENSG00000151247), EIF4E3 (ENSG00000163412)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4E type 1B — A6NMX2 (reviewed: A6NMX2)

All UniProt accessions (3): A6NMX2, D6RHE2, H0Y8X3

UniProt curated annotations — full annotation on UniProt →

Function. Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structure.

Subunit / interactions. eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G.

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

RefSeq proteins (2): NP_001092878, NP_001362291 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001040	TIF_eIF_4E	Family
IPR019770	TIF_eIF_4E_CS	Conserved_site
IPR023398	TIF_eIF4e-like	Homologous_superfamily

Pfam: PF01652

UniProt features (12 total): region of interest 4, binding site 4, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NMX2-F1	83.43	0.72

Functional residue map

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

Ligand- & substrate-binding residues (4): 230–232; 81–82; 127–128; 182–187

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): GOBP_TRANSLATIONAL_INITIATION, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOCC_RNA_CAP_BINDING_COMPLEX, GOBP_REGULATION_OF_TRANSLATION, KEGG_INSULIN_SIGNALING_PATHWAY, GOMF_RNA_CAP_BINDING, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, MARTENS_TRETINOIN_RESPONSE_UP, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_4F_COMPLEX, GOMF_RNA_7_METHYLGUANOSINE_CAP_BINDING, ZNF423_TARGET_GENES, WP_FOCAL_ADHESION_PI3KAKTMTORSIGNALING, WP_PI3KAKT_SIGNALING

GO Biological Process (3): translational initiation (GO:0006413), regulation of translation (GO:0006417), translation (GO:0006412)

GO Molecular Function (4): RNA 7-methylguanosine cap binding (GO:0000340), translation initiation factor activity (GO:0003743), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (2): eukaryotic translation initiation factor 4F complex (GO:0016281), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
translational initiation	2
formation of translation initiation ternary complex	1
metabolic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
RNA cap binding	1
translation factor activity	1
nucleic acid binding	1
binding	1
cytoplasm	1
RNA cap binding complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4E1B	LSM14B	Q9BX40	787
EIF4E1B	DDX6	P26196	716
EIF4E1B	PABPC1L	Q4VXU2	648
EIF4E1B	CPEB1	Q9BZB8	612
EIF4E1B	LSM14A	Q8ND56	609
EIF4E1B	EIF4ENIF1	Q9NRA8	543
EIF4E1B	NCBP1	Q09161	507
EIF4E1B	IDNK	Q5T6J7	462
EIF4E1B	PATL2	C9JE40	454
EIF4E1B	EIF5B	O60841	445
EIF4E1B	DPY19L4	Q7Z388	438
EIF4E1B	EIF4G1	Q04637	437
EIF4E1B	KPNA7	A9QM74	427
EIF4E1B	TELO2	Q9Y4R8	414
EIF4E1B	EIF4G2	P78344	410

IntAct

7 interactions, top by confidence:

A	B	Type	Score
EIF4E1B	EIF4EBP1	psi-mi:“MI:0915”(physical association)	0.670
EIF4EBP1	EIF4E1B	psi-mi:“MI:0914”(association)	0.670
EIF4E	EIF4E1B	psi-mi:“MI:0914”(association)	0.350
EIF4E	POTEF	psi-mi:“MI:0914”(association)	0.350
EIF4EBP1	EIF4E1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): EIF4EBP1 (Two-hybrid), EIF4E1B (Affinity Capture-MS), EIF4E1B (Affinity Capture-MS), EIF4E1B (Affinity Capture-MS)

ESM2 similar proteins: A0A075QQ08, A0A1D8EJF9, A0A2J6L8Y7, A0A3Q7FGP1, A4K436, A6NMX2, D3UW26, D4AB66, F1M5F3, F1N2W9, F1QWK4, O08908, O43272, O60336, O81481, O88984, O94851, P29557, P41111, P58797, Q0VGM9, Q28ET8, Q2KHI9, Q2T9Z1, Q3UTA9, Q496Y0, Q4V908, Q4VQY1, Q4VQY3, Q5R752, Q5RE34, Q5RJZ1, Q63788, Q66HY7, Q66UV4, Q6GR08, Q6H1L8, Q6NS57, Q6NU27, Q8BML1

Diamond homologs: A0A075QQ08, A0A1D8EJF9, A0A1U8F5V2, A0A1U8GR65, A0A2J6L8Y7, A0A3Q7FGP1, A0A3Q7I7R4, A0A445AGS0, A3RCV9, A6NMX2, A7KWF8, C6ZJZ3, C7SG33, D3UW26, K0P2S0, M1J8U6, M1JJT8, O04663, O23252, O45551, O60573, O61955, O74743, O77210, O81481, O81482, P06730, P07260, P0DXI0, P0DXI5, P29338, P29557, P48597, P48598, P48599, P48600, P56570, P63073, P63074, P78954

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1655 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176643081:G:GC	acceptor_loss	1.0000
5:176643081:GGTGA:G	acceptor_gain	1.0000
5:176643730:TGGGC:T	donor_gain	1.0000
5:176643731:GGGC:G	donor_gain	1.0000
5:176643731:GGGCG:G	donor_gain	1.0000
5:176643732:GGC:G	donor_gain	1.0000
5:176643732:GGCG:G	donor_gain	1.0000
5:176643733:GC:G	donor_gain	1.0000
5:176643733:GCG:G	donor_gain	1.0000
5:176643733:GCGTG:G	donor_loss	1.0000
5:176643735:G:C	donor_loss	1.0000
5:176643735:G:GG	donor_gain	1.0000
5:176643736:T:A	donor_loss	1.0000
5:176644353:AT:A	acceptor_gain	1.0000
5:176644353:ATG:A	acceptor_gain	1.0000
5:176644353:ATGG:A	acceptor_gain	1.0000
5:176645127:CA:C	acceptor_loss	1.0000
5:176645128:A:AG	acceptor_gain	1.0000
5:176645128:AG:A	acceptor_gain	1.0000
5:176645128:AGGAT:A	acceptor_gain	1.0000
5:176645129:G:GA	acceptor_gain	1.0000
5:176645129:GG:G	acceptor_gain	1.0000
5:176645129:GGA:G	acceptor_gain	1.0000
5:176645129:GGAT:G	acceptor_gain	1.0000
5:176645129:GGATG:G	acceptor_gain	1.0000
5:176645239:AGACG:A	donor_gain	1.0000
5:176645240:GACG:G	donor_gain	1.0000
5:176645240:GACGG:G	donor_gain	1.0000
5:176645241:ACG:A	donor_gain	1.0000
5:176645242:CG:C	donor_gain	1.0000

AlphaMissense

1583 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:176645150:G:C	W127C	0.997
5:176645150:G:T	W127C	0.997
5:176645181:T:A	W138R	0.997
5:176645181:T:C	W138R	0.997
5:176644434:T:C	F119L	0.996
5:176644436:C:A	F119L	0.996
5:176644436:C:G	F119L	0.996
5:176645473:T:A	W191R	0.996
5:176645473:T:C	W191R	0.996
5:176644435:T:C	F119S	0.993
5:176645148:T:A	W127R	0.993
5:176645148:T:C	W127R	0.993
5:176645475:G:C	W191C	0.993
5:176645475:G:T	W191C	0.993
5:176645915:T:G	Y222D	0.993
5:176645467:G:C	A189P	0.992
5:176645183:G:C	W138C	0.991
5:176645183:G:T	W138C	0.991
5:176645446:C:A	R182S	0.991
5:176645232:T:A	W155R	0.990
5:176645232:T:C	W155R	0.990
5:176645878:A:C	K209N	0.990
5:176645878:A:T	K209N	0.990
5:176644434:T:A	F119I	0.989
5:176645182:G:C	W138S	0.988
5:176645429:G:A	G176E	0.988
5:176643640:T:A	W68R	0.987
5:176643640:T:C	W68R	0.987
5:176645447:G:C	R182P	0.987
5:176645916:A:C	Y222S	0.987

dbSNP variants (sampled 300 via entrez): RS1000148037 (5:176635496 G>C), RS1000308166 (5:176640888 C>T), RS1000401913 (5:176646544 C>T), RS1000524445 (5:176643786 C>A), RS1000865120 (5:176636312 T>C,G), RS1000874693 (5:176642177 G>A), RS1000994975 (5:176630524 G>A), RS1001048750 (5:176630335 G>C), RS1001131776 (5:176631619 T>C), RS1001469703 (5:176637848 AT>A), RS1001729241 (5:176642188 G>C), RS1001999694 (5:176639820 G>A), RS1002134149 (5:176630238 A>C,G), RS1002485267 (5:176641533 T>C), RS1002517875 (5:176641335 AT>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
apatinib	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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