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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CPSF4
cleavage and polyadenylation specific factor 4
Chromosome 7 · 7q22.1
NCBI Gene: 10898Ensembl: ENSG00000160917.15HGNC: HGNC:2327UniProt: B7Z7B0
99PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mRNA 3'-end processingRNA bindingnucleoplasmmRNA cleavage and polyadenylation specificity factor complexinfluenzadengue diseaseneurodegenerative diseaseAbnormality of the skeletal system
✦AI Summary

CPSF4 (cleavage and polyadenylation specific factor 4) is a core component of the CPSF complex that mediates pre-mRNA 3'-end formation by recognizing AAUAAA signals and facilitating cleavage and poly(A) addition 1. Beyond its canonical role in mRNA processing, CPSF4 functions as a multifaceted oncogene across multiple cancer types. In hepatocellular carcinoma, elevated CPSF4 expression reduces circRNA levels, disrupting miRNA-mediated gene silencing and promoting tumor proliferation 1. In lung adenocarcinoma and colon cancer, CPSF4 acts as a transcriptional regulator of hTERT, activating telomerase and driving unlimited cell proliferation 23. In triple-negative breast cancer, CPSF4 regulates alternative splicing of HMG20B to enhance cancer cell progression 4. In lung cancer, CPSF4 promotes tumor-initiating phenotypes through VEGF/NRP2/TAZ signaling, conferring chemoresistance 5. Clinical evidence consistently demonstrates that high CPSF4 expression correlates with poor prognosis across cancer types and associates with aggressive features in prostate cancer 6. Additionally, CPSF4 interacts with influenza NS1 protein to suppress interferon-stimulated gene translation, highlighting its role in viral pathogenesis 7. These findings establish CPSF4 as a therapeutic target in cancer treatment.

Sources cited
1
CPSF4 is upregulated in HCC, reduces circRNA levels, and disrupts miRNA-mediated gene silencing to promote hepatocellular carcinoma tumorigenicity
PMID: 34103682
2
CPSF4 activates hTERT transcription and telomerase activity in lung adenocarcinoma; high CPSF4 expression predicts poor prognosis
PMID: 24618080
3
CPSF4 promotes colon cancer progression by transcriptionally regulating hTERT expression through cooperation with NF-κB1
PMID: 31301362
4
CPSF4 regulates alternative splicing of HMG20B to promote triple-negative breast cancer progression and correlates with unfavorable prognosis
PMID: 39731153
5
High CPSF4 expression in prostate cancer correlates with Gleason grades and promotes cell migration and cycle dysregulation
PMID: 37629142
6
CPSF4 promotes lung cancer tumor-initiating phenotype and chemoresistance through VEGF/NRP2/TAZ signaling axis
PMID: 36567417
7
miR-4458 targets CPSF4 3'-UTR to suppress breast cancer cell growth by downregulating downstream targets COX-2 and hTERT
PMID: 30970220
8
Influenza A virus NS1 protein binds CPSF4 to suppress interferon-stimulated gene translation and antiviral immunity
PMID: 28554059
Disease Associationsⓘ20
influenzaOpen Targets
0.37Weak
dengue diseaseOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.23Weak
Abnormality of the skeletal systemOpen Targets
0.20Weak
Abruptio PlacentaeOpen Targets
0.17Weak
smoking initiationOpen Targets
0.13Weak
attention deficit hyperactivity disorderOpen Targets
0.10Suggestive
substance abuseOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
smoking behaviorOpen Targets
0.07Suggestive
ulcerative colitisOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
posterior cortical atrophyOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
oral squamous cell carcinomaOpen Targets
0.04Suggestive
prostate cancerOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPRD2Shared pathway100%TSEN34Protein interaction100%TSEN54Protein interaction100%TSEN15Protein interaction100%CPSF3Protein interaction99%WDR33Protein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
73%
Lung
71%
Liver
64%
Brain
44%
Heart
44%
Gene Interaction Network
Click a node to explore
CPSF4RPRD2TSEN34TSEN54TSEN15CPSF3WDR33
PROTEIN STRUCTURE
Preparing viewer…
PDB7K95 · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.29 [0.18–0.48]
RankingsWhere CPSF4 stands among ~20K protein-coding genes
  • #4,828of 20,598
    Most Researched99 · top quartile
  • #2,802of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedCPSF4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma.
PMID: 34103682
Oncogene · 2021
1.00
2
CPSF4 activates telomerase reverse transcriptase and predicts poor prognosis in human lung adenocarcinomas.
PMID: 24618080
Mol Oncol · 2014
0.90
3
Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT.
PMID: 31301362
Biochim Biophys Acta Mol Cell Res · 2019
0.80
4
CPSF4-mediated regulation of alternative splicing of HMG20B facilitates the progression of triple-negative breast cancer.
PMID: 39731153
J Transl Med · 2024
0.70
5
Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.
PMID: 37629142
Int J Mol Sci · 2023
0.60