EIF4E2

protein-coding

eukaryotic translation initiation factor 4E family member 2

Gene summary

Enables RNA 7-methylguanosine cap binding activity; mRNA cap binding activity; and ubiquitin protein ligase binding activity. Involved in negative regulation of translational initiation; negative regulation of type I interferon-mediated signaling pathway; and rescue of stalled cytosolic ribosome. Acts upstream of with a positive effect on miRNA-mediated gene silencing by inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

EIF4EL3

MANE transcript

NM_004846.4

Inheritance

—

ClinVar variants

U:30

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr2:232,550,659-232,583,644

External References & Databases

Ensembl (ENSG00000135930)

Transcript & Mutation Effects

hg38 • Region Span ~33.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EIF4E2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 23

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004846.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			25 clinvar			25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	30	0	0	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004846.4	RefSeq	NP_004837.1	7	MANE Select
ENST00000258416.8	Ensembl	ENSP00000258416.3	7	MANE Select
NM_001276336.2	RefSeq	NP_001263265.1	7	Standard
NM_001276337.2	RefSeq	NP_001263266.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
mTOR signaling pathway - Homo sapiens (human)
HIF-1 signaling pathway - Homo sapiens (human)
RNA transport - Homo sapiens (human)
Longevity regulating pathway - Homo sapiens (human)

Biological Process

in utero embryonic development
translational initiation
negative regulation of translation

Molecular Function

RNA cap binding
RNA 7-methylguanosine cap binding
RNA binding
translation initiation factor activity
protein binding

Cellular Component

cytosol
mRNA cap binding complex
eukaryotic translation initiation factor 4F complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258416
Coding exons: 7
Length: 33593
Individuals with no LoFs: 125745
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125748
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	66	145	0.456	0.00000841	1640
Missense (PolyPhen)		6	30.561	0.19633		414
Synonymous	0.0985	48	48.9	0.982	0.00000261	429
Loss of Function	2.96	3	15.7	0.192	9.44e-7	156

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity). {ECO:0000250|UniProtKB:Q8BMB3, ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:25624349, ECO:0000269|PubMed:9582349}.;

Recessive Scores

pRec: 0.0914

Intolerance Scores

LoFtool: 0.331
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium