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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ENY2
ENY2 transcription and export complex 2 subunit
Chromosome 8 · 8q23.1
NCBI Gene: 56943Ensembl: ENSG00000120533.13HGNC: HGNC:24449UniProt: Q9NPA8
65PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription FactorTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of DNA-templated transcriptiontranscription export complex 2nuclear pore nuclear basketSAGA complexneurodegenerative diseaselysosomal storage diseasehepatocellular carcinomacolorectal carcinoma
✦AI Summary

ENY2 is a multifunctional transcriptional regulator that coordinates gene expression through its integration into multiple protein complexes. As a component of the SAGA complex, ENY2 participates in histone H2B deubiquitination and transcription activation 1, working with ATXN7L3 to orchestrate activities of multiple deubiquitinating enzymes including USP22, USP27X, and USP51 1. ENY2 also functions within the TREX-2 complex to facilitate mRNA export from the nucleus through nuclear pores 2, though recent evidence suggests this is its primary dedicated function distinct from other TREX-2 components 3. ENY2 serves as an adapter molecule integrating transcription, mRNA processing, and nuclear export 4, and participates in nuclear receptor-mediated transactivation 5. Clinically, ENY2 is upregulated across multiple cancer types and functions as both a diagnostic and prognostic biomarker 6. ENY2 depletion induces nucleolar stress through NPM1 release, triggering p53-dependent and p53-independent tumor suppression pathways 7. These findings position ENY2 as a potential therapeutic target for cancer management, though its role in human cells requires further investigation 8.

Sources cited
1
ENY2 coordinates H2B deubiquitination with ATXN7L3 and multiple DUBs; ENY2 depletion increases H2Bub1 levels and is required for cell proliferation
PMID: 27132940
2
ENY2 as a TREX-2 component is involved in mRNA export to cytoplasm through nuclear pores
PMID: 23591820
3
ENY2 is specifically dedicated to mRNA export function within TREX-2, distinguishing it from other complex components with additional cellular roles
PMID: 24291146
4
ENY2 functions as an adapter molecule in multiple protein complexes (SAGA, TREX-2, THO) integrating different stages of gene expression
PMID: 20090412
5
ENY2 is required for nuclear receptor-mediated transactivation
PMID: 18206972
6
ENY2 is significantly upregulated in multiple cancer types and serves as a diagnostic and prognostic biomarker with independent prognostic value in head and neck cancers
PMID: 36862319
7
ENY2 depletion induces nucleolar stress through NPM1 release, triggering both p53-dependent and p53-independent tumor suppression mechanisms
PMID: 41642454
8
ENY2/Sus1 has broad roles in mRNA biogenesis including histone deubiquitination, mRNA export, and gene gating; its role in human cells and disease associations remain largely unknown
PMID: 23057668
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.56Moderate
lysosomal storage diseaseOpen Targets
0.27Weak
hepatocellular carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
intelligenceOpen Targets
0.06Suggestive
schizophreniaOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
tooth diseaseOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
rhabdomyolysisOpen Targets
0.03Suggestive
dementiaOpen Targets
0.02Suggestive
androgenetic alopeciaOpen Targets
0.02Suggestive
Reunion island Larsen syndromeOpen Targets
0.02Suggestive
Reunion Island's Larsen syndromeOpen Targets
0.02Suggestive
infectionOpen Targets
0.01Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.01Suggestive
insulinomaOpen Targets
0.01Suggestive
bacteriemiaOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
posterior cortical atrophyOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SGF29Protein interaction100%DR1Protein interaction100%KAT2AProtein interaction100%SARS1Protein interaction100%TADA2AProtein interaction100%TAF5Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
60%
Liver
56%
Lung
44%
Heart
41%
Ovary
41%
Gene Interaction Network
Click a node to explore
ENY2SGF29DR1KAT2ASARS1TADA2ATAF5
PROTEIN STRUCTURE
Preparing viewer…
PDB4DHX · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.64Intermediate
Observed/Expected LoF0.32 [0.16–0.74]
RankingsWhere ENY2 stands among ~20K protein-coding genes
  • #7,164of 20,598
    Most Researched65
  • #5,803of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedENY2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Sus1/ENY2: a multitasking protein in eukaryotic gene expression.
PMID: 23057668
Crit Rev Biochem Mol Biol · 2012
1.00
2
Human TREX2 components PCID2 and centrin 2, but not ENY2, have distinct functions in protein export and co-localize to the centrosome.
PMID: 24291146
Exp Cell Res · 2014
0.90
3
ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth.
PMID: 27132940
Mol Cell · 2016
0.80
4
ENY2 transcription and export complex 2 subunit deficiency induces nucleolar stress to inhibit tumor progression through NPM1/MDM2/p53-dependent and -independent responses.
PMID: 41642454
Cell Oncol (Dordr) · 2026
0.70
5
An integrative analysis of enhancer of yellow 2 homolog (ENY2) as a molecular biomarker in pan-cancer.
PMID: 36862319
Funct Integr Genomics · 2023
0.60