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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF3H
eukaryotic translation initiation factor 3 subunit H
Chromosome 8 · 8q23.3-q24.11
NCBI Gene: 8667Ensembl: ENSG00000147677.13HGNC: HGNC:3273UniProt: O15372
198PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
translation initiation factor activityRNA bindingprotein bindingmetal-dependent deubiquitinase activityneurodegenerative diseasecolonic neoplasmcolorectal cancerrectal neoplasm
✦AI Summary

EIF3H (eukaryotic translation initiation factor 3 subunit H) functions as a component of the eIF3 complex required for protein synthesis initiation, but also exhibits deubiquitinase activity that promotes cancer progression. As part of the eIF3 complex, EIF3H facilitates ribosome assembly and mRNA recruitment for translation initiation 1. Beyond its canonical translation role, EIF3H acts as a deubiquitinating enzyme belonging to the JAMM superfamily, stabilizing oncogenic proteins through removal of K48-linked ubiquitin chains 234. In colorectal cancer, EIF3H stabilizes HAX1 and activates RAF-MEK-ERK signaling 5, while in hepatocellular carcinoma it stabilizes OGT and inhibits ferroptosis 3. EIF3H also stabilizes β-catenin in anaplastic thyroid cancer, promoting Wnt signaling activation 4. The protein enhances translation of oncogenic mRNAs like BRD4 through interaction with METTL3, promoting mRNA circularization 16. EIF3H is consistently overexpressed across multiple cancers and correlates with poor prognosis 253. Genetic polymorphisms in EIF3H represent major risk factors for colorectal cancer 7. These findings establish EIF3H as both a translation regulator and oncogenic deubiquitinase, making it a promising therapeutic target.

Sources cited
1
EIF3H interacts with METTL3 to enhance translation through mRNA circularization and promotes oncogenic transformation
PMID: 30232453
2
EIF3H acts as a deubiquitinating enzyme that stabilizes Snail protein in esophageal cancer
PMID: 32867821
3
EIF3H stabilizes HAX1 through deubiquitination and activates RAF-MEK-ERK signaling in colorectal cancer
PMID: 38514606
4
EIF3H belongs to JAMM superfamily and functions as deubiquitinase of OGT, inhibiting ferroptosis in hepatocellular carcinoma
PMID: 37559097
5
EIF3H deubiquitinates and stabilizes β-catenin by removing K48-linked ubiquitin chains in anaplastic thyroid cancer
PMID: 39984062
6
EIF3H interacts with METTL3 to regulate BRD4 translation in colorectal cancer
PMID: 35164758
7
EIF3H genetic polymorphisms represent major risk factors for colorectal cancer
PMID: 37527660
8
EIF3H stabilizes CCND1 protein and promotes intrahepatic cholangiocarcinoma progression
PMID: 36350008
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
colonic neoplasmOpen Targets
0.42Moderate
colorectal cancerOpen Targets
0.39Weak
rectal neoplasmOpen Targets
0.33Weak
anal neoplasmOpen Targets
0.33Weak
Abdominal Aortic AneurysmOpen Targets
0.29Weak
type 2 diabetes mellitusOpen Targets
0.26Weak
polyp of large intestineOpen Targets
0.25Weak
diabetes mellitusOpen Targets
0.24Weak
otosclerosisOpen Targets
0.23Weak
androgenetic alopeciaOpen Targets
0.22Weak
breast carcinomaOpen Targets
0.22Weak
benign colon neoplasmOpen Targets
0.22Weak
cecal neoplasmOpen Targets
0.21Weak
Abnormality of the gastrointestinal tractOpen Targets
0.20Weak
prostate carcinomaOpen Targets
0.20Weak
polyp of colonOpen Targets
0.19Weak
colon carcinomaOpen Targets
0.18Weak
placenta praeviaOpen Targets
0.17Weak
ankylosing spondylitisOpen Targets
0.17Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EIF1AXProtein interaction100%EIF4A1Protein interaction100%EIF4G1Protein interaction100%PSMD7Protein interaction100%SELENOPProtein interaction100%EIF3AProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
93%
Heart
86%
Brain
65%
Lung
61%
Liver
36%
Gene Interaction Network
Click a node to explore
EIF3HEIF1AXEIF4A1EIF4G1PSMD7SELENOPEIF3A
PROTEIN STRUCTURE
Preparing viewer…
PDB8PPL · 2.65 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.80LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.42–0.80]
RankingsWhere EIF3H stands among ~20K protein-coding genes
  • #2,139of 20,598
    Most Researched198 · top quartile
  • #6,639of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedEIF3H
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
EIF3H promotes aggressiveness of esophageal squamous cell carcinoma by modulating Snail stability.
PMID: 32867821
J Exp Clin Cancer Res · 2020
1.00
2
The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression.
PMID: 38514606
Nat Commun · 2024
0.90
3
Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3-eIF3h interaction.
PMID: 35164758
Mol Cancer · 2022
0.80
4
mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis.
PMID: 30232453
Nature · 2018
0.70
5
Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.
PMID: 38190401
PLoS Negl Trop Dis · 2024
0.60